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Sample records for adult glucose homeostasis

  1. Utility of Childhood Glucose Homeostasis Variables in Predicting Adult Diabetes and Related Cardiometabolic Risk Factors

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    Nguyen, Quoc Manh; Srinivasan, Sathanur R.; Xu, Ji-Hua; Chen, Wei; Kieltyka, Lyn; Berenson, Gerald S.

    2009-01-01

    OBJECTIVE This study examines the usefulness of childhood glucose homeostasis variables (glucose, insulin, and insulin resistance index [homeostasis model assessment of insulin resistance {HOMA-IR}]) in predicting pre-diabetes and type 2 diabetes and related cardiometabolic risk factors in adulthood. RESEARCH DESIGN AND METHODS This retrospective cohort study consisted of normoglycemic (n = 1,058), pre-diabetic (n = 37), and type 2 diabetic (n = 25) adults aged 19–39 years who were followed o...

  2. Effects of prenatal caffeine exposure on glucose homeostasis of adult offspring rats

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    Kou, Hao; Wang, Gui-hua; Pei, Lin-guo; Zhang, Li; Shi, Chai; Guo, Yu; Wu, Dong-fang; Wang, Hui

    2017-12-01

    Epidemiological evidences show that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR). The IUGR offspring also present glucose intolerance and type 2 diabetes mellitus after maturity. We have previously demonstrated that PCE induced IUGR and increased susceptibility to adult metabolic syndrome in rats. This study aimed to further investigate the effects of PCE on glucose homeostasis in adult offspring rats. Pregnant rats were administered caffeine (120 mg/kg/day, intragastrically) from gestational days 11 to 20. PCE offspring presented partial catch-up growth pattern after birth, characterizing by the increased body weight gain rates. Meanwhile, PCE had no significant influences on the basal blood glucose and insulin phenotypes of adult offspring but increased the glucose tolerance, glucose-stimulated insulin section and β cell sensitivity to glucose in female progeny. The insulin sensitivity of both male and female PCE offspring were enhanced accompanied with reduced β cell fraction and mass. Western blotting results revealed that significant augmentation in protein expression of hepatic insulin signaling elements of PCE females, including insulin receptor (INSR), insulin receptor substrate 1 (IRS-1) and the phosphorylation of serine-threonine protein kinase (Akt), was also potentiated. In conclusion, we demonstrated that PCE reduced the pancreatic β mass but increased the glucose tolerance in adult offspring rats, especially for females. The adaptive compensatory enhancement of β cell responsiveness to glucose and elevated insulin sensitivity mainly mediated by upregulated hepatic insulin signaling might coordinately contribute to the increased glucose tolerance.

  3. Childhood cardiorespiratory fitness, muscular fitness and adult measures of glucose homeostasis.

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    Fraser, Brooklyn J; Blizzard, Leigh; Schmidt, Michael D; Juonala, Markus; Dwyer, Terence; Venn, Alison J; Magnussen, Costan G

    2018-02-14

    To assess whether childhood cardiorespiratory fitness (CRF) and muscular fitness phenotypes (strength, power, endurance) predict adult glucose homeostasis measures. Prospective longitudinal study. Study examining participants who had physical fitness measured in childhood (aged 7-15 years) and who attended follow-up clinics approximately 20 years later and provided a fasting blood sample which was tested for glucose and insulin. Physical fitness measurements included muscular strength (right and left grip, shoulder flexion, shoulder and leg extension), power (standing long jump distance) and endurance (number of push-ups in 30s), and CRF (1.6km run duration). In adulthood, fasting glucose and insulin levels were used to derive glucose homeostasis measures of insulin resistance (HOMA2-IR) and beta cell function (HOMA2-β). A standard deviation increase in childhood CRF or muscular strength (males) was associated with fasting glucose (CRF: β=-0.06mmol/L), fasting insulin (CRF: β=-0.73mU/L; strength: β=-0.40mU/L), HOMA2-IR (CRF: β=-0.06; strength: β=-0.05) and HOMA2-β (CRF: β=-3.06%; strength: β=-2.62%) in adulthood, independent of the alternative fitness phenotype (all p0.06). CRF and muscular fitness in childhood were inversely associated with measures of fasting insulin, insulin resistance and beta cell function in adulthood. Childhood CRF and muscular fitness could both be potential independent targets for strategies to help reduce the development of adverse glucose homeostasis. Copyright © 2018 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  4. Sleep apnea predicts distinct alterations in glucose homeostasis and biomarkers in obese adults with normal and impaired glucose metabolism

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    Hill Nathan R

    2010-12-01

    Full Text Available Abstract Background Notwithstanding previous studies supporting independent associations between obstructive sleep apnea (OSA and prevalence of diabetes, the underlying pathogenesis of impaired glucose regulation in OSA remains unclear. We explored mechanisms linking OSA with prediabetes/diabetes and associated biomarker profiles. We hypothesized that OSA is associated with distinct alterations in glucose homeostasis and biomarker profiles in subjects with normal (NGM and impaired glucose metabolism (IGM. Methods Forty-five severely obese adults (36 women without certain comorbidities/medications underwent anthropometric measurements, polysomnography, and blood tests. We measured fasting serum glucose, insulin, selected cytokines, and calculated homeostasis model assessment estimates of insulin sensitivity (HOMA-IS and pancreatic beta-cell function (HOMA-B. Results Both increases in apnea-hypopnea index (AHI and the presence of prediabetes/diabetes were associated with reductions in HOMA-IS in the entire cohort even after adjustment for sex, race, age, and BMI (P = 0.003. In subjects with NGM (n = 30, OSA severity was associated with significantly increased HOMA-B (a trend towards decreased HOMA-IS independent of sex and adiposity. OSA-related oxyhemoglobin desaturations correlated with TNF-α (r=-0.76; P = 0.001 in women with NGM and with IL-6 (rho=-0.55; P = 0.035 in women with IGM (n = 15 matched individually for age, adiposity, and AHI. Conclusions OSA is independently associated with altered glucose homeostasis and increased basal beta-cell function in severely obese adults with NGM. The findings suggest that moderate to severe OSA imposes an excessive functional demand on pancreatic beta-cells, which may lead to their exhaustion and impaired secretory capacity over time. The two distinct biomarker profiles linking sleep apnea with NGM and IGM via TNF-α and IL-6 have been discerned in our study to suggest that sleep apnea and particularly

  5. Effects of Ramadan fasting on glucose homeostasis and adiponectin levels in healthy adult males.

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    Gnanou, Justin V; Caszo, Brinnell A; Khalil, Khalifah M; Abdullah, Shahidah L; Knight, Victor F; Bidin, Mohd Z

    2015-01-01

    Adiponectin is a hormone secreted by adipocytes during the fasting phase of the fast-fed cycle. Ramadan fasting involves prolonged fasting for up to twelve hours and thus could lead to increased secretion of adiponectin by adipocytes. However, studies on the role of adiponectin on glucose and body weight homeostasis during Ramadan fasting is still a matter of controversy. Thus the specific aim of this study was to assess the effect of fasting during Ramadan on the adiponectin levels, body weight and glucose homeostasis in healthy male Malaysian subjects. Twenty healthy male (19-23 years) Muslim subjects were followed up during the fasting month of Ramadan. Anthropometry and blood samples were taken one week before and during the fourth week of fasting. Plasma glucose, insulin and adiponectin were estimated and insulin sensitivity indices were estimated using the Homeostasis Model Assessment. Subjects experienced a significant decrease in body weight (2.4 %, p Ramadan fasting in young healthy individuals has a positive impact on the maintenance of glucose homeostasis. It also shows that adiponectin levels dropped along with significant loss in weight. We feel caloric restriction during the Ramadan fasting is in itself sufficient to improve insulin sensitivity in healthy individuals.

  6. Partial ablation of adult Drosophila insulin-producing neurons modulates glucose homeostasis and extends life span without insulin resistance.

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    Haselton, Aaron; Sharmin, Effat; Schrader, Janel; Sah, Megha; Poon, Peter; Fridell, Yih-Woei C

    2010-08-01

    In Drosophila melanogaster (D. melanogaster), neurosecretory insulin-like peptide-producing cells (IPCs), analogous to mammalian pancreatic beta cells are involved in glucose homeostasis. Extending those findings, we have developed in the adult fly an oral glucose tolerance test and demonstrated that IPCs indeed are responsible for executing an acute glucose clearance response. To further develop D. melanogaster as a relevant system for studying age-associated metabolic disorders, we set out to determine the impact of adult-specific partial ablation of IPCs (IPC knockdown) on insulin-like peptide (ILP) action, metabolic outcomes and longevity. Interestingly, while IPC knockdown flies are hyperglycemic and glucose intolerant, these flies remain insulin sensitive as measured by peripheral glucose disposal upon insulin injection and serine phosphorylation of a key insulin-signaling molecule, Akt. Significant increases in stored glycogen and triglyceride levels as well as an elevated level of circulating lipid measured in adult IPC knockdown flies suggest profound modulation in energy metabolism. Additional physiological outcomes measured in those flies include increased resistance to starvation and impaired female fecundity. Finally, increased life span and decreased mortality rates measured in IPC knockdown flies demonstrate that it is possible to modulate ILP action in adult flies to achieve life span extension without insulin resistance. Taken together, we have established and validated an invertebrate genetic system to further investigate insulin action, metabolic homeostasis and regulation of aging regulated by adult IPCs.

  7. Neuroscience of glucose homeostasis

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    La Fleur, S E; Fliers, E; Kalsbeek, A

    2014-01-01

    Plasma glucose concentrations are homeostatically regulated and maintained within strict boundaries. Several mechanisms are in place to increase glucose output when glucose levels in the circulation drop as a result of glucose utilization, or to decrease glucose output and increase tissue glucose

  8. Perinatal bisphenol A exposure and adult glucose homeostasis: identifying critical windows of exposure.

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    Jingli Liu

    Full Text Available Bisphenol A (BPA is a widespread endocrine-disrupting chemical used as the building block for polycarbonate plastics. Epidemiological evidence has correlated BPA exposure with higher risk of heart disease and type 2 diabetes. However, it remains unknown whether there are critical windows of susceptibility to BPA exposure on the development of dysglycemia. This study was an attempt to investigate the critical windows and the long-term consequences of perinatal exposure to BPA on glucose homeostasis. Pregnant mice were given either vehicle or BPA (100 µg/kg/day at different time of perinatal stage: 1 on days 1-6 of pregnancy (P1-P6, preimplantation exposure; 2 from day 6 of pregnancy until postnatal day (PND 0 (P6-PND0, fetal exposure; 3 from lactation until weaning (PND0-PND21, neonatal exposure; and 4 from day 6 of gestation until weaning (P6-PND21, fetal and neonatal exposure. At 3, 6 and 8 months of age, offspring in each group were challenged with glucose and insulin tolerance tests. Then islet morphometry and β-cell function were measured. The glucose homeostasis was impaired in P6-PND0 mice from 3 to 6 months of age, and this continued to 8 months in males, but not females. While in PND0-PND21 and P6-PND21 BPA-treated groups, only the 3-month-old male offspring developed glucose intolerance. Moreover, at the age of 3 months, perinatal exposure to BPA resulted in the increase of β-cell mass mainly due to the coordinate changes in cell replication, neogenesis, and apoptosis. The alterations of insulin secretion and insulin sensitivity, rather than β-cell mass, were consistent with the development of glucose intolerance. Our findings suggest that BPA may contribute to metabolic disorders relevant to glucose homeostasis and the effects of BPA were dose, sex, and time-dependent. Fetal development stage may be the critical window of susceptibility to BPA exposure.

  9. Alterations in Adiposity and Glucose Homeostasis in Adult Gasp-1 Overexpressing Mice

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    Luce Périè

    2017-12-01

    Full Text Available Background/Aims: Myostatin is known as a powerful negative regulator of muscle growth playing a key role in skeletal muscle homeostasis. Recent studies revealed that myostatin-deficient mice lead to an increase of insulin sensitivity, a decrease of adiposity and a resistance to obesity, showing that myostatin can also impact on metabolism. Thus, myostatin appeared as a potential therapeutic target to treat insulin resistance. Methods: We generated transgenic mice overexpressing Gasp-1, a myostatin inhibitor. Results: Surprisingly, we found that these mice gained weight with age due to an increase in fat mass associated with ectopic fat accumulation. In addition, these mice developed an adipocyte hypertrophy, hyperglycemia, hyperinsulinemia, muscle and hepatic insulin resistance. Understanding the molecular networks controlling this insulin resistance responsiveness in overexpressing Gasp-1 mice is essential. Molecular analyses revealed a deregulation of adipokines and muscle cytokines expression, but also an increase in plasma myostatin levels. The increase in myostatin bioactivity by a positive feedback mechanism in the Tg(Gasp-1 transgenic mice could lead to this combination of phenotypes. Conclusion: Altogether, these data suggested that overexpressing Gasp-1 mice develop most of the symptoms associated with metabolic syndrome and could be a relevant model for the study of obesity or type 2 diabetes.

  10. Coffee Consumption, Newly Diagnosed Diabetes, and Other Alterations in Glucose Homeostasis: A Cross-Sectional Analysis of the Longitudinal Study of Adult Health (ELSA-Brasil)

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    Yarmolinsky, James; Mueller, Noel T.; Duncan, Bruce B.; Bisi Molina, Maria del Carmen; Goulart, Alessandra C.; Schmidt, Maria Inês

    2015-01-01

    Introduction Observational studies have reported fairly consistent inverse associations between coffee consumption and risk of type 2 diabetes, but this association has been little investigated with regard to lesser degrees of hyperglycemia and other alterations in glucose homeostasis. Additionally, the association between coffee consumption and diabetes has been rarely investigated in South American populations. We examined the cross-sectional relationships of coffee intake with newly diagnosed diabetes and measures of glucose homeostasis, insulin sensitivity, and insulin secretion, in a large Brazilian cohort of middle-aged and elderly individuals. Methods We used baseline data from 12,586 participants of the Longitudinal Study of Adult Health (ELSA-Brasil). Logistic regression analyses were performed to examine associations between coffee consumption and newly diagnosed diabetes. Analysis of covariance was used to assess coffee intake in relation to two-hour glucose from an oral glucose tolerance test, fasting glucose, glycated hemoglobin, fasting and –2-hour postload insulin and measures of insulin sensitivity. Results We found an inverse association between coffee consumption and newly diagnosed diabetes, after adjusting for multiple covariates [23% and 26% lower odds of diabetes for those consuming coffee 2–3 and >3 times per day, respectively, compared to those reporting never or almost never consuming coffee, (p = .02)]. An inverse association was also found for 2-hour postload glucose [Never/almost never: 7.57 mmol/L, ≤1 time/day: 7.48 mmol/L, 2-3 times/day: 7.22 mmol/L, >3 times/day: 7.12 mol/L, p3 times/day: 262.2 pmol/L, p = 0.0005) but not with fasting insulin concentrations (p = .58). Conclusion Our present study provides further evidence of a protective effect of coffee on risk of adult-onset diabetes. This effect appears to act primarily, if not exclusively, through postprandial, as opposed to fasting, glucose homeostasis. PMID:25978631

  11. Coffee Consumption, Newly Diagnosed Diabetes, and Other Alterations in Glucose Homeostasis: A Cross-Sectional Analysis of the Longitudinal Study of Adult Health (ELSA-Brasil.

    Directory of Open Access Journals (Sweden)

    James Yarmolinsky

    Full Text Available Observational studies have reported fairly consistent inverse associations between coffee consumption and risk of type 2 diabetes, but this association has been little investigated with regard to lesser degrees of hyperglycemia and other alterations in glucose homeostasis. Additionally, the association between coffee consumption and diabetes has been rarely investigated in South American populations. We examined the cross-sectional relationships of coffee intake with newly diagnosed diabetes and measures of glucose homeostasis, insulin sensitivity, and insulin secretion, in a large Brazilian cohort of middle-aged and elderly individuals.We used baseline data from 12,586 participants of the Longitudinal Study of Adult Health (ELSA-Brasil. Logistic regression analyses were performed to examine associations between coffee consumption and newly diagnosed diabetes. Analysis of covariance was used to assess coffee intake in relation to two-hour glucose from an oral glucose tolerance test, fasting glucose, glycated hemoglobin, fasting and -2-hour postload insulin and measures of insulin sensitivity.We found an inverse association between coffee consumption and newly diagnosed diabetes, after adjusting for multiple covariates [23% and 26% lower odds of diabetes for those consuming coffee 2-3 and >3 times per day, respectively, compared to those reporting never or almost never consuming coffee, (p = .02]. An inverse association was also found for 2-hour postload glucose [Never/almost never: 7.57 mmol/L, ≤1 time/day: 7.48 mmol/L, 2-3 times/day: 7.22 mmol/L, >3 times/day: 7.12 mol/L, p3 times/day: 262.2 pmol/L, p = 0.0005 but not with fasting insulin concentrations (p = .58.Our present study provides further evidence of a protective effect of coffee on risk of adult-onset diabetes. This effect appears to act primarily, if not exclusively, through postprandial, as opposed to fasting, glucose homeostasis.

  12. Brain glucose sensing, counterregulation, and energy homeostasis.

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    Marty, Nell; Dallaporta, Michel; Thorens, Bernard

    2007-08-01

    Neuronal circuits in the central nervous system play a critical role in orchestrating the control of glucose and energy homeostasis. Glucose, beside being a nutrient, is also a signal detected by several glucose-sensing units that are located at different anatomical sites and converge to the hypothalamus to cooperate with leptin and insulin in controlling the melanocortin pathway.

  13. Atypical antipsychotics and glucose homeostasis.

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    Bergman, Richard N; Ader, Marilyn

    2005-04-01

    Persistent reports have linked atypical antipsychotics with diabetes, yet causative mechanisms responsible for this linkage are unclear. Goals of this review are to outline the pathogenesis of nonimmune diabetes and to survey the available literature related to why antipsychotics may lead to this disease. We accessed the literature regarding atypical antipsychotics and glucose homeostasis using PubMed. The search included English-language publications from 1990 through October 2004. Keywords used included atypical antipsychotics plus one of the following: glucose, insulin, glucose tolerance, obesity, or diabetes. In addition, we culled information from published abstracts from several national and international scientific meetings for the years 2001 through 2004, including the American Diabetes Association, the International Congress on Schizophrenia Research, and the American College of Neuropsychopharmacology. The latter search was necessary because of the paucity of well-controlled prospective studies. We examined publications with significant new data or publications that contributed to the overall comprehension of the impact of atypical antipsychotics on glucose metabolism. We favored original peer-reviewed articles and were less likely to cite single case studies and/or anecdotal information. Approximately 75% of the fewer than 150 identified articles were examined and included in this review. Validity of data was evaluated using the existence of peer-review status as well as our own experience with methodology described in the specific articles. The metabolic profile caused by atypical antipsychotic treatment resembles type 2 diabetes. These agents cause weight gain in treated subjects and may induce obesity in both visceral and subcutaneous depots, as occurs in diabetes. Insulin resistance, usually associated with obesity, occurs to varying degrees with different antipsychotics, although more comparative studies with direct assessment of resistance are

  14. Association of glucose homeostasis measures with heart rate variability among Hispanic/Latino adults without diabetes: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

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    Meyer, Michelle L; Gotman, Nathan M; Soliman, Elsayed Z; Whitsel, Eric A; Arens, Raanan; Cai, Jianwen; Daviglus, Martha L; Denes, Pablo; González, Hector M; Moreiras, Juan; Talavera, Gregory A; Heiss, Gerardo

    2016-03-16

    Reduced heart rate variability (HRV), a measure of cardiac autonomic function, is associated with an increased risk of cardiovascular disease (CVD) and mortality. Glucose homeostasis measures are associated with reduced cardiac autonomic function among those with diabetes, but inconsistent associations have been reported among those without diabetes. This study aimed to examine the association of glucose homeostasis measures with cardiac autonomic function among diverse Hispanic/Latino adults without diabetes. The Hispanic community Health Study/Study of Latinos (HCHS/SOL; 2008-2011) used two-stage area probability sampling of households to enroll 16,415 self-identified Hispanics/Latinos aged 18-74 years from four USA communities. Resting, standard 12-lead electrocardiogram recordings were used to estimate the following ultrashort-term measures of HRV: RR interval (RR), standard deviation of all normal to normal RR (SDNN) and root mean square of successive differences in RR intervals (RMSSD). Multivariable regression analysis was used to estimate associations between glucose homeostasis measures with HRV using data from 11,994 adults without diabetes (mean age 39 years; 52 % women). Higher fasting glucose was associated with lower RR, SDNN, and RMSSD. Fasting insulin and the homeostasis model assessment of insulin resistance was negatively associated with RR, SDNN, and RMSSD, and the association was stronger among men compared with women. RMSSD was, on average, 26 % lower in men with higher fasting insulin and 29 % lower in men with lower insulin resistance; for women, the corresponding estimates were smaller at 4 and 9 %, respectively. Higher glycated hemoglobin was associated with lower RR, SDNN, and RMSSD in those with abdominal adiposity, defined by sex-specific cut-points for waist circumference, after adjusting for demographics and medication use. There were no associations between glycated hemoglobin and HRV measures among those without abdominal adiposity

  15. A mathematical model of brain glucose homeostasis

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    Kimura Hidenori

    2009-11-01

    Full Text Available Abstract Background The physiological fact that a stable level of brain glucose is more important than that of blood glucose suggests that the ultimate goal of the glucose-insulin-glucagon (GIG regulatory system may be homeostasis of glucose concentration in the brain rather than in the circulation. Methods In order to demonstrate the relationship between brain glucose homeostasis and blood hyperglycemia in diabetes, a brain-oriented mathematical model was developed by considering the brain as the controlled object while the remaining body as the actuator. After approximating the body compartmentally, the concentration dynamics of glucose, as well as those of insulin and glucagon, are described in each compartment. The brain-endocrine crosstalk, which regulates blood glucose level for brain glucose homeostasis together with the peripheral interactions among glucose, insulin and glucagon, is modeled as a proportional feedback control of brain glucose. Correlated to the brain, long-term effects of psychological stress and effects of blood-brain-barrier (BBB adaptation to dysglycemia on the generation of hyperglycemia are also taken into account in the model. Results It is shown that simulation profiles obtained from the model are qualitatively or partially quantitatively consistent with clinical data, concerning the GIG regulatory system responses to bolus glucose, stepwise and continuous glucose infusion. Simulations also revealed that both stress and BBB adaptation contribute to the generation of hyperglycemia. Conclusion Simulations of the model of a healthy person under long-term severe stress demonstrated that feedback control of brain glucose concentration results in elevation of blood glucose level. In this paper, we try to suggest that hyperglycemia in diabetes may be a normal outcome of brain glucose homeostasis.

  16. The resist diabetes trial: Rationale, design, and methods of a hybrid efficacy/effectiveness intervention trial for resistance training maintenance to improve glucose homeostasis in older prediabetic adults.

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    Marinik, Elaina L; Kelleher, Sarah; Savla, Jyoti; Winett, Richard A; Davy, Brenda M

    2014-01-01

    Advancing age is associated with reduced levels of physical activity, increased body weight and fat, decreased lean body mass, and a high prevalence of type 2 diabetes (T2D). Resistance training (RT) increases muscle strength and lean body mass, and reduces risk of T2D among older adults. The Resist Diabetes trial will determine if a social cognitive theory (SCT)-based intervention improves RT maintenance in older, prediabetic adults, using a hybrid efficacy/effectiveness approach. Sedentary, overweight/obese (BMI: 25-39.9 kg/m(2)) adults aged 50-69 (N = 170) with prediabetes (impaired fasting glucose and/or impaired glucose tolerance) completed a supervised 3-month RT (2×/wk) initiation phase and were then randomly assigned (N = 159; 94% retention) to one of two 6-month maintenance conditions: SCT or standard care. The SCT intervention consisted of faded contacts compared to standard care. Participants continue RT at an approved, self-selected community facility during maintenance. A subsequent 6-month period involves no contact for both conditions. Assessments occur at baseline and months 3 (post-initiation), 9 (post-intervention), and 15 (six months after no contact). Primary outcomes are prediabetes indices (i.e., impaired fasting and 2-hour glucose concentration) and strength. Secondary measures include insulin sensitivity, beta-cell responsiveness, and disposition index (oral glucose and C-peptide minimal model); adherence; body composition; and SCT measures. Resist Diabetes is the first trial to examine the effectiveness of a high fidelity SCT-based intervention for maintaining RT in older adults with prediabetes to improve glucose homeostasis. Successful application of SCT constructs for RT maintenance may support translation of our RT program for diabetes prevention into community settings. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Hypothalamic neurones governing glucose homeostasis.

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    Coppari, R

    2015-06-01

    The notion that the brain directly controls the level of glucose in the blood (glycaemia) independent of its known action on food intake and body weight has been known ever since 1849. That year, the French physiologist Dr Claude Bernard reported that physical puncture of the floor of the fourth cerebral ventricle rapidly leads to an increased level of sugar in the blood (and urine) in rabbits. Despite this important discovery, it took approximately 150 years before significant efforts aimed at understanding the underlying mechanism of brain-mediated control of glucose metabolism were made. Technological developments allowing for genetically-mediated manipulation of selected molecular pathways in a neurone-type-specific fashion unravelled the importance of specific molecules in specific neuronal populations. These neuronal pathways govern glucose metabolism in the presence and even in the absence of insulin. Also, a peculiarity of these pathways is that certain biochemically-defined neurones govern glucose metabolism in a tissue-specific fashion. © 2015 British Society for Neuroendocrinology.

  18. [Contribution of the kidney to glucose homeostasis].

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    Segura, Julián; Ruilope, Luis Miguel

    2013-09-01

    The kidney is involved in glucose homeostasis through three major mechanisms: renal gluconeogenesis, renal glucose consumption, and glucose reabsorption in the proximal tubule. Glucose reabsorption is one of the most important physiological functions of the kidney, allowing full recovery of filtered glucose, elimination of glucose from the urine, and prevention of calorie loss. Approximately 90% of the glucose is reabsorbed in the S1 segment of the proximal tubule, where glucose transporter-2 (GLUT2) and sodium-glucose transporter-2 (SGLT2) are located, while the remaining 10% is reabsorbed in the S3 segment by SGLT1 and GLUT1 transporters. In patients with hyperglycemia, the kidney continues to reabsorb glucose, thus maintaining hyperglycemia. Most of the renal glucose reabsorption is mediated by SGLT2. Several experimental and clinical studies suggest that pharmacological blockade of this transporter might be beneficial in the management of hyperglycemia in patients with type 2 diabetes. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  19. Cognitive Performance: A Cross-Sectional Study on Serum Vitamin D and Its Interplay With Glucose Homeostasis in Dutch Older Adults.

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    Brouwer-Brolsma, Elske M; Dhonukshe-Rutten, Rosalie A M; van Wijngaarden, Janneke P; van de Zwaluw, Nikita L; in 't Veld, Paulette H; Wins, Sophie; Swart, Karin M A; Enneman, Anke W; Ham, Annelies C; van Dijk, Suzanne C; van Schoor, Natasja M; van der Velde, Nathalie; Uitterlinden, Andre G; Lips, Paul; Kessels, Roy P C; Steegenga, Wilma T; Feskens, Edith J M; de Groot, Lisette C P G M

    2015-07-01

    First, the association between serum 25-hydroxyvitamin D (25[OH]D) and cognitive performance was examined. Second, we assessed whether there was evidence for an interplay between 25(OH)D and glucose homeostasis in the association with cognitive performance. Associations were studied using cross-sectional data of 776 (3 domains) up to 2722 (1 domain) Dutch community-dwelling older adults, aged 65 years or older. Serum 25(OH)D, plasma glucose, and insulin concentrations were obtained. Cognitive performance was assessed with an extensive cognitive test battery. Prevalence ratios (PRs) were calculated to quantify the association between 25(OH)D and cognition; poor performance was defined as the worst 10% of the distribution of the cognitive scores. The overall median MMSE score was 29 (IQR 28-30). Higher serum 25(OH)D was associated with better attention and working memory, PR 0.50 (95% CI 0.29-0.84) for the third serum 25(OH)D tertile, indicating a 50% lower probability of being a poor performer than participants in the lowest tertile. Beneficial trends were shown for 25(OH)D with executive function and episodic memory. Serum 25(OH)D was not associated with plasma glucose or insulin. Plasma insulin only modified the association between serum 25(OH)D and executive function (P for interaction: .001), suggesting that the improvement in executive function with high 25(OH)D concentrations is stronger in participants with high plasma insulin concentrations compared with those with low plasma insulin concentrations. Higher 25(OH)D concentrations significantly associated with better attention and working memory performance. This study does not demonstrate an interplay between serum 25(OH)D and glucose homeostasis in the association with cognitive performance. Copyright © 2015 AMDA - The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

  20. Blood spot-based measures of glucose homeostasis and diabetes prevalence in a nationally representative population of young US adults.

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    Nguyen, Quynh C; Whitsel, Eric A; Tabor, Joyce W; Cuthbertson, Carmen C; Wener, Mark H; Potter, Alan J; Halpern, Carolyn T; Killeya-Jones, Ley A; Hussey, Jon M; Suchindran, Chirayath; Harris, Kathleen Mullan

    2014-12-01

    We investigated understudied biomarker-based diabetes among young US adults, traditionally characterized by low cardiovascular disease risk. We examined 15,701 participants aged 24 to 32 years at Wave IV of the National Longitudinal Study of Adolescent Health (Add Health, 2008). The study used innovative and relatively noninvasive methods to collect capillary whole blood via finger prick at in-home examinations in all 50 states. Assays of dried blood spots produced reliable and accurate values of HbA1c. Reliability was lower for fasting glucose and lowest for random glucose. Mean (SD) HbA1c was 5.6% (0.8%). More than a quarter (27.4%) had HbA1c-defined prediabetes. HbA1c was highest in the black, non-Hispanic race/ethnic group, inversely associated with education, and more common among the overweight/obese and physically inactive. The prevalence of diabetes defined by previous diagnosis or use of antidiabetic medication was 2.9%. Further incorporating HbA1c and glucose values, the prevalence increased to 6.8%, and among these participants, 38.9% had a previous diagnosis of diabetes (i.e., aware). Among those aware, 37.6% were treated and 64.0% were controlled (i.e., HbA1c young adults faces a historically high risk of diabetes but there is ample opportunity for early detection and intervention. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Impact of intermittent fasting on glucose homeostasis.

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    Varady, Krista A

    2016-07-01

    This article provides an overview of the most recent human trials that have examined the impact of intermittent fasting on glucose homeostasis. Our literature search retrieved one human trial of alternate day fasting, and three trials of Ramadan fasting published in the past 12 months. Current evidence suggests that 8 weeks of alternate day fasting that produces mild weight loss (4% from baseline) has no effect on glucose homeostasis. As for Ramadan fasting, decreases in fasting glucose, insulin, and insulin resistance have been noted after 4 weeks in healthy normal weight individuals with mild weight loss (1-2% from baseline). However, Ramadan fasting may have little impact on glucoregulatory parameters in women with polycystic ovarian syndrome who failed to observe weight loss. Whether intermittent fasting is an effective means of regulating glucose homeostasis remains unclear because of the scarcity of studies in this area. Large-scale, longer-term randomized controlled trials will be required before the use of fasting can be recommended for the prevention and treatment of metabolic diseases.

  2. Pak3 promotes cell cycle exit and differentiation of β-cells in the embryonic pancreas and is necessary to maintain glucose homeostasis in adult mice.

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    Piccand, Julie; Meunier, Aline; Merle, Carole; Jia, Zhengping; Barnier, Jean-Vianney; Gradwohl, Gérard

    2014-01-01

    The transcription factor neurogenin3 (Ngn3) triggers islet cell differentiation in the developing pancreas. However, little is known about the molecular mechanisms coupling cell cycle exit and differentiation in Ngn3(+) islet progenitors. We identified a novel effector of Ngn3 endocrinogenic function, the p21 protein-activated kinase Pak3, known to control neuronal differentiation and implicated in X-linked intellectual disability in humans. We show that Pak3 expression is initiated in Ngn3(+) endocrine progenitor cells and next maintained in maturing hormone-expressing cells during pancreas development as well as in adult islet cells. In Pak3-deficient embryos, the proliferation of Ngn3(+) progenitors and β-cells is transiently increased concomitantly with an upregulation of Ccnd1. β-Cell differentiation is impaired at E15.5 but resumes at later stages. Pak3-deficient mice do not develop overt diabetes but are glucose intolerant under high-fat diet (HFD). In the intestine, Pak3 is expressed in enteroendocrine cells but is not necessary for their differentiation. Our results indicate that Pak3 is a novel regulator of β-cell differentiation and function. Pak3 acts downstream of Ngn3 to promote cell cycle exit and differentiation in the embryo by a mechanism that might involve repression of Ccnd1. In the adult, Pak3 is required for the proper control of glucose homeostasis under challenging HFD.

  3. Cognitive Performance: A Cross-Sectional Study on Serum Vitamin D and Its Interplay With Glucose Homeostasis in Dutch Older Adults

    NARCIS (Netherlands)

    Brouwer-Brolsma, Elske M.; Dhonukshe-Rutten, Rosalie A. M.; van Wijngaarden, Janneke P.; van de Zwaluw, Nikita L.; In 't Veld, Paulette H.; Wins, Sophie; Swart, Karin M. A.; Enneman, Anke W.; Ham, Annelies C.; van Dijk, Suzanne C.; van Schoor, Natasja M.; van der Velde, Nathalie; Uitterlinden, Andre G.; Lips, Paul; Kessels, Roy P. C.; Steegenga, Wilma T.; Feskens, Edith J. M.; de Groot, Lisette C. P. G. M.

    2015-01-01

    First, the association between serum 25-hydroxyvitamin D (25[OH]D) and cognitive performance was examined. Second, we assessed whether there was evidence for an interplay between 25(OH)D and glucose homeostasis in the association with cognitive performance. Associations were studied using

  4. Cognitive Performance: A Cross-Sectional Study on Serum Vitamin D and Its Interplay With Glucose Homeostasis in Dutch Older Adults

    NARCIS (Netherlands)

    Brouwer-Brolsma, E.M.; Dhonukshe-Rutten, R.A.M.; van Wijngaarden, J.P.; van der Zwaluw, N.L.; in 't Veld, P.H.; Wins, S.; Swart, C.M.A.; Enneman, A.W.; van der Ham, A.C.; van Dijk, S.C.; van Schoor, N.M.; van der Velde, N.; Uitterlinden, A. G.; Lips, P.; Kessels, R.P.C.; Steegenga, W.T.; Feskens, E.J.M.; de Groot, L.C.P.G.

    2015-01-01

    Objectives: First, the association between serum 25-hydroxyvitamin D (25[OH]D) and cognitive performance was examined. Second, we assessed whether there was evidence for an interplay between 25(OH)D and glucose homeostasis in the association with cognitive performance. Design, Setting, and

  5. Cognitive Performance: A Cross-Sectional Study on Serum Vitamin D and Its Interplay With Glucose Homeostasis in Dutch Older Adults

    NARCIS (Netherlands)

    Brouwer-Brolsma, E.M.; Dhonukshe-Rutten, R.A.; Wijngaarden, J.P. van; Zwaluw, N.L. van der; Veld, P.H. In 't; Wins, S.; Swart, K.M.; Enneman, A.W.; Ham, A.C. van der; Dijk, S.C. van; Schoor, N.M. van; Velde, N. van der; Uitterlinden, A.G.; Lips, P.; Kessels, R.P.C.; Steegenga, W.T.; Feskens, E.J.M.; Groot, L.C. de

    2015-01-01

    OBJECTIVES: First, the association between serum 25-hydroxyvitamin D (25[OH]D) and cognitive performance was examined. Second, we assessed whether there was evidence for an interplay between 25(OH)D and glucose homeostasis in the association with cognitive performance. DESIGN, SETTING, AND

  6. Cognitive performance: a cross-sectional study on serum vitamin D and its interplay with glucose homeostasis in Dutch older adults

    NARCIS (Netherlands)

    Brouwer-Brolsma, E.M.; Dhonukshe-Rutten, R.A.M.; Wijngaarden, van J.P.; Zwaluw, van der N.L.; Veld, in 't P.H.; Wins, S.; Swart, K.M.A.; Enneman, A.W.; Ham, A.C.; Dijk, van S.C.; Schoor, van N.M.; Velde, van der N.; Uitterlinden, A.G.; Lips, P.; Kessels, R.P.C.; Steegenga, W.T.; Feskens, E.J.M.; Groot, de C.P.G.M.

    2015-01-01

    Objectives First, the association between serum 25-hydroxyvitamin D (25[OH]D) and cognitive performance was examined. Second, we assessed whether there was evidence for an interplay between 25(OH)D and glucose homeostasis in the association with cognitive performance. Design, Setting, and

  7. Cognitive performance: A cross-sectional study on serum vitamin D and its interplay with glucose homeostasis in Dutch older adults

    NARCIS (Netherlands)

    Brouwer-Brolsma, E.M.; Dhonukshe-Rutten, R.A.M.; Wijngaarden, J.P. van; Zwaluw, N.L. van der; Veld, P.H. in 't; Wins, S.; Swart, K.M.A.; Enneman, A.W.; Ham, A.C.; Dijk, S.C. van; Schoor, N.M. van; Velde, N. van der; Uitterlinden, A.G.; Lips, P.J.; Kessels, R.P.C.; Steegenga, W.T.; Feskens, E.J.M.; Groot, L.C.P.G.M. de

    2015-01-01

    Objectives First, the association between serum 25-hydroxyvitamin D (25[OH]D) and cognitive performance was examined. Second, we assessed whether there was evidence for an interplay between 25(OH)D and glucose homeostasis in the association with cognitive performance. Design, Setting, and

  8. [Glucose homeostasis and gut-brain connection].

    Science.gov (United States)

    De Vadder, Filipe; Mithieux, Gilles

    2015-02-01

    Since the XIX(th) century, the brain has been known for its role in regulating food intake (via the control of hunger sensation) and glucose homeostasis. Further interest has come from the discovery of gut hormones, which established a clear link between the gut and the brain in regulating glucose and energy homeostasis. The brain has two particular structures, the hypothalamus and the brainstem, which are sensitive to information coming either from peripheral organs or from the gut (via circulating hormones or nutrients) about the nutritional status of the organism. However, the efforts for a better understanding of these mechanisms have allowed to unveil a new gut-brain neural axis as a key regulator of the metabolic status of the organism. Certain nutrients control the hypothalamic homeostatic function via this axis. In this review, we describe how the gut is connected to the brain via different neural pathways, and how the interplay between these two organs drives the energy balance. © 2015 médecine/sciences – Inserm.

  9. Physical activity, fitness, glucose homeostasis, and brain morphology in twins.

    Science.gov (United States)

    Rottensteiner, Mirva; Leskinen, Tuija; Niskanen, Eini; Aaltonen, Sari; Mutikainen, Sara; Wikgren, Jan; Heikkilä, Kauko; Kovanen, Vuokko; Kainulainen, Heikki; Kaprio, Jaakko; Tarkka, Ina M; Kujala, Urho M

    2015-03-01

    The main aim of the present study (FITFATTWIN) was to investigate how physical activity level is associated with body composition, glucose homeostasis, and brain morphology in young adult male monozygotic twin pairs discordant for physical activity. From a population-based twin cohort, we systematically selected 10 young adult male monozygotic twin pairs (age range, 32-36 yr) discordant for leisure time physical activity during the past 3 yr. On the basis of interviews, we calculated a mean sum index for leisure time and commuting activity during the past 3 yr (3-yr LTMET index expressed as MET-hours per day). We conducted extensive measurements on body composition (including fat percentage measured by dual-energy x-ray absorptiometry), glucose homeostasis including homeostatic model assessment index and insulin sensitivity index (Matsuda index, calculated from glucose and insulin values from an oral glucose tolerance test), and whole brain magnetic resonance imaging for regional volumetric analyses. According to pairwise analysis, the active twins had lower body fat percentage (P = 0.029) and homeostatic model assessment index (P = 0.031) and higher Matsuda index (P = 0.021) compared with their inactive co-twins. Striatal and prefrontal cortex (subgyral and inferior frontal gyrus) brain gray matter volumes were larger in the nondominant hemisphere in active twins compared with those in inactive co-twins, with a statistical threshold of P physical activity is associated with improved glucose homeostasis and modulation of striatum and prefrontal cortex gray matter volume, independent of genetic background. The findings may contribute to later reduced risk of type 2 diabetes and mobility limitations.

  10. Association of SSTR2 Polymorphisms and Glucose Homeostasis Phenotypes

    OpenAIRE

    Sutton, Beth S.; Palmer, Nicholette D.; Langefeld, Carl D.; Xue, Bingzhong; Proctor, Alexandria; Ziegler, Julie T.; Haffner, Steven M.; Norris, Jill M.; Bowden, Donald W.

    2009-01-01

    OBJECTIVE This study evaluated the influence of somatostatin receptor type 2 (SSTR2) polymorphisms on measures of glucose homeostasis in the Insulin Resistance Atherosclerosis Family Study (IRASFS). SSTR2 is a G-protein?coupled receptor that, in response to somatostatin, mediates inhibition of insulin, glucagon, and growth hormone release and thus may affect glucose homeostasis. RESEARCH DESIGN AND METHODS Ten single nucleotide polymorphisms (SNPs) spanning the gene were chosen using a SNP de...

  11. Multilevel control of glucose homeostasis by adenylyl cyclase 8

    NARCIS (Netherlands)

    Raoux, Matthieu; Vacher, Pierre; Papin, Julien; Picard, Alexandre; Kostrzewa, Elzbieta; Devin, Anne; Gaitan, Julien; Limon, Isabelle; Kas, Martien J.; Magnan, Christophe; Lang, Jochen

    2015-01-01

    Aims/hypothesis: Nutrient homeostasis requires integration of signals generated by glucose metabolism and hormones. Expression of the calcium-stimulated adenylyl cyclase ADCY8 is regulated by glucose and the enzyme is capable of integrating signals from multiple pathways. It may thus have an

  12. Breast Milk Hormones and Regulation of Glucose Homeostasis

    Directory of Open Access Journals (Sweden)

    Francesco Savino

    2011-01-01

    Full Text Available Growing evidence suggests that a complex relationship exists between the central nervous system and peripheral organs involved in energy homeostasis. It consists in the balance between food intake and energy expenditure and includes the regulation of nutrient levels in storage organs, as well as in blood, in particular blood glucose. Therefore, food intake, energy expenditure, and glucose homeostasis are strictly connected to each other. Several hormones, such as leptin, adiponectin, resistin, and ghrelin, are involved in this complex regulation. These hormones play a role in the regulation of glucose metabolism and are involved in the development of obesity, diabetes, and metabolic syndrome. Recently, their presence in breast milk has been detected, suggesting that they may be involved in the regulation of growth in early infancy and could influence the programming of energy balance later in life. This paper focuses on hormones present in breast milk and their role in glucose homeostasis.

  13. Roles of the Gut in Glucose Homeostasis

    DEFF Research Database (Denmark)

    Holst, Jens Juul; Gribble, Fiona; Horowitz, Michael

    2016-01-01

    The gastrointestinal tract plays a major role in the regulation of postprandial glucose profiles. Gastric emptying is a highly regulated process, which normally ensures a limited and fairly constant delivery of nutrients and glucose to the proximal gut. The subsequent digestion and absorption...... of nutrients are associated with the release of a set of hormones that feeds back to regulate subsequent gastric emptying and regulates the release of insulin, resulting in downregulation of hepatic glucose production and deposition of glucose in insulin-sensitive tissues. These remarkable mechanisms normally...... keep postprandial glucose excursions low, regardless of the load of glucose ingested. When the regulation of emptying is perturbed (e.g., pyloroplasty, gastric sleeve or gastric bypass operation), postprandial glycemia may reach high levels, sometimes followed by profound hypoglycemia. This article...

  14. Cooperation between brain and islet in glucose homeostasis and diabetes

    Science.gov (United States)

    Schwartz, Michael W.; Seeley, Randy J.; Tschöp, Matthias H.; Woods, Stephen C.; Morton, Gregory J.; Myers, Martin G.; D'Alessio, David

    2014-01-01

    Although a prominent role for the brain in glucose homeostasis was proposed by scientists in the nineteenth century, research throughout most of the twentieth century focused on evidence that the function of pancreatic islets is both necessary and sufficient to explain glucose homeostasis, and that diabetes results from defects of insulin secretion, action or both. However, insulin-independent mechanisms, referred to as ‘glucose effectiveness’, account for roughly 50% of overall glucose disposal, and reduced glucose effectiveness also contributes importantly to diabetes pathogenesis. Although mechanisms underlying glucose effectiveness are poorly understood, growing evidence suggests that the brain can dynamically regulate this process in ways that improve or even normalize glycaemia in rodent models of diabetes. Here we present evidence of a brain-centred glucoregulatory system (BCGS) that can lower blood glucose levels via both insulin-dependent and -independent mechanisms, and propose a model in which complex and highly coordinated interactions between the BCGS and pancreatic islets promote normal glucose homeostasis. Because activation of either regulatory system can compensate for failure of the other, defects in both may be required for diabetes to develop. Consequently, therapies that target the BCGS in addition to conventional approaches based on enhancing insulin effects may have the potential to induce diabetes remission, whereas targeting just one typically does not. PMID:24201279

  15. The effect of metformin on glucose homeostasis during moderate exercise

    DEFF Research Database (Denmark)

    Hansen, Merethe; Palsøe, Marie K.; Helge, Jørn Wulff

    2015-01-01

    OBJECTIVE: We investigated the role of metformin on glucose kinetics during moderate exercise. RESEARCH DESIGN AND METHODS: Before, during, and after a 45-min bout of exercise at 60% VO2max, glucose kinetics were determined by isotope tracer technique in patients with type 2 diabetes mellitus....... CONCLUSIONS: Metformin has a positive effect on glucose homeostasis during exercise....... with metformin treatment (DM2+Met) or without metformin treatment (DM2) and in healthy control subjects (CON) matched for BMI and age. Glucoregulatory hormones and metabolites were measured throughout the study. RESULTS: Plasma glucose concentration was unchanged during exercise in CON but decreased in DM2...

  16. Dietary fructose and glucose differentially affect lipid and glucose homeostasis.

    Science.gov (United States)

    Schaefer, Ernst J; Gleason, Joi A; Dansinger, Michael L

    2009-06-01

    Absorbed glucose and fructose differ in that glucose largely escapes first-pass removal by the liver, whereas fructose does not, resulting in different metabolic effects of these 2 monosaccharides. In short-term controlled feeding studies, dietary fructose significantly increases postprandial triglyceride (TG) levels and has little effect on serum glucose concentrations, whereas dietary glucose has the opposite effects. When dietary glucose and fructose have been directly compared at approximately 20-25% of energy over a 4- to 6-wk period, dietary fructose caused significant increases in fasting TG and LDL cholesterol concentrations, whereas dietary glucose did not, but dietary glucose did increase serum glucose and insulin concentrations in the postprandial state whereas dietary fructose did not. When fructose at 30-60 g ( approximately 4-12% of energy) was added to the diet in the free-living state, there were no significant effects on lipid or glucose biomarkers. Sucrose and high-fructose corn syrup (HFCS) contain approximately equal amounts of fructose and glucose and no metabolic differences between them have been noted. Controlled feeding studies at more physiologic dietary intakes of fructose and glucose need to be conducted. In our view, to decrease the current high prevalence of obesity, dyslipidemia, insulin resistance, and diabetes, the focus should be on restricting the intake of excess energy, sucrose, HFCS, and animal and trans fats and increasing exercise and the intake of vegetables, vegetable oils, fish, fruit, whole grains, and fiber.

  17. nfluence of antidepressants on glucose homeostasis : effects and mechanisms

    NARCIS (Netherlands)

    Derijks, H.J.

    2009-01-01

    Depression has shown to be a common morbidity in patients with diabetes mellitus and comorbid depression in diabetes mellitus patients is frequently treated with antidepressants. It has been postulated that antidepressants may interfere with glucose homeostasis and that the interference of

  18. Exploring the role of glucagon in glucose homeostasis

    NARCIS (Netherlands)

    Dongen, Maria Gertrud Jobina van

    2015-01-01

    The aim of this thesis was to gain further insight into the role of glucagon in glucose homeostasis in healthy volunteers and type 2 diabetes mellitus (T2DM) patients, and to explore the novel antisense glucagon receptor antagonist. Chapter 2 showed that the effect of meal replacers containing

  19. Asiatic acid influences glucose homeostasis in P. berghei murine ...

    African Journals Online (AJOL)

    Background: Glucose homeostasis derangement is a common pathophysiology of malaria whose aetiology is still controversial. The Plasmodium parasite, immunological and inflammatory responses, as well as chemotherapeutics currently used cause hypoglycaemia in malaria. Anti-parasitic and anti-disease drugs are ...

  20. The effect of altitude hypoxia on glucose homeostasis in men

    DEFF Research Database (Denmark)

    Larsen, J J; Hansen, J M; Olsen, Niels Vidiendal

    1997-01-01

    1. Exposure to altitude hypoxia elicits changes in glucose homeostasis with increases in glucose and insulin concentrations within the first few days at altitude. Both increased and unchanged hepatic glucose production (HGP) have previously been reported in response to acute altitude hypoxia...... (noradrenaline and adrenaline) and day 7 (adrenaline), but not at sea level. 4. In conclusion, insulin action decreases markedly in response to two days of altitude hypoxia, but improves with more prolonged exposure. HGP is always unchanged. The changes in insulin action may in part be explained by the changes...

  1. Glucocorticoid receptor polymorphism in obesity and glucose homeostasis.

    Science.gov (United States)

    Majer-Łobodzińska, Agnieszka; Adamiec-Mroczek, Joanna

    2017-01-01

    Glucocorticoid receptor (GR) activity plays a significant role in the etiology of obesity and is essential for glucose homeostasis, the development of hyperinsulinaemia and subsequent increased fat deposition. Several polymorphisms in the GR gene have been described, and at least three of them seem to be associated with altered glucocorticoid sensitivity and changes in glucose homeostasis, and other metabolic parameters. The N363S polymorphism has been associated with increased sensitivity to glucocorticoides, increased insulin response to dexamethasone and increased plasma glucose level. BclI polymorphism is associated with increased abdominal obesity, hyperinsulinaemia and increased insulin resistance. Another polymorphism, ER22/23EK, in contrast to the others, is associated with relative resistance to glucocoricides actions and more beneficial metabolic profile-lower insulin resistance level, decreased lower cardiovascular risk and subseuent prolongation of life time. More research is still needed to understand the mechanisms behind these associations at the molecular level.

  2. CNS-targets in control of energy and glucose homeostasis.

    Science.gov (United States)

    Kleinridders, André; Könner, A Christine; Brüning, Jens C

    2009-12-01

    The exceeding efforts in understanding the signals initiated by nutrients and hormones in the central nervous system (CNS) to regulate glucose and energy homeostasis have largely revolutionized our understanding of the neurocircuitry in control of peripheral metabolism. The ability of neurons to sense nutrients and hormones and to adopt a coordinated response to these signals is of crucial importance in controlling food intake, energy expenditure, glucose and lipid metabolism. Anatomical lesion experiments, pharmacological inhibition of signaling pathways, and, more recently, the analysis of conditional mouse mutants with modifications of hormone and nutrient signaling in defined neuronal populations have broadened our understanding of these complex neurocircuits. This review summarizes recent findings regarding the role of the CNS in sensing and transmitting nutritional and hormonal signals to control energy and glucose homeostasis and aims to define them as potential novel drug targets for the treatment of obesity and type 2 diabetes mellitus.

  3. Glucose is necessary to maintain neurotransmitter homeostasis during synaptic activity in cultured glutamatergic neurons

    DEFF Research Database (Denmark)

    Bak, Lasse K; Schousboe, Arne; Sonnewald, Ursula

    2006-01-01

    Glucose is the primary energy substrate for the adult mammalian brain. However, lactate produced within the brain might be able to serve this purpose in neurons. In the present study, the relative significance of glucose and lactate as substrates to maintain neurotransmitter homeostasis was inves......Glucose is the primary energy substrate for the adult mammalian brain. However, lactate produced within the brain might be able to serve this purpose in neurons. In the present study, the relative significance of glucose and lactate as substrates to maintain neurotransmitter homeostasis...... was investigated. Cultured cerebellar (primarily glutamatergic) neurons were superfused in medium containing [U-13C]glucose (2.5 mmol/L) and lactate (1 or 5 mmol/L) or glucose (2.5 mmol/L) and [U-13C]lactate (1 mmol/L), and exposed to pulses of N-methyl-D-aspartate (300 micromol/L), leading to synaptic activity...... significantly during induced depolarization. In contrast, at both concentrations of extracellular lactate, the metabolism of [U-13C]glucose was increased during neuronal depolarization. The role of glucose and lactate as energy substrates during vesicular release as well as transporter-mediated influx...

  4. Upper intestinal lipids regulate energy and glucose homeostasis.

    Science.gov (United States)

    Cheung, Grace W C; Kokorovic, Andrea; Lam, Tony K T

    2009-09-01

    Upon the entry of nutrients into the small intestine, nutrient sensing mechanisms are activated to allow the body to adapt appropriately to the incoming nutrients. To date, mounting evidence points to the existence of an upper intestinal lipid-induced gut-brain neuronal axis to regulate energy homeostasis. Moreover, a recent discovery has also revealed an upper intestinal lipid-induced gut-brain-liver neuronal axis involved in the regulation of glucose homeostasis. In this mini-review, we will focus on the mechanisms underlying the activation of these respective neuronal axes by upper intestinal lipids.

  5. Gut-Brain Glucose Signaling in Energy Homeostasis.

    Science.gov (United States)

    Soty, Maud; Gautier-Stein, Amandine; Rajas, Fabienne; Mithieux, Gilles

    2017-06-06

    Intestinal gluconeogenesis is a recently identified function influencing energy homeostasis. Intestinal gluconeogenesis induced by specific nutrients releases glucose, which is sensed by the nervous system surrounding the portal vein. This initiates a signal positively influencing parameters involved in glucose control and energy management controlled by the brain. This knowledge has extended our vision of the gut-brain axis, classically ascribed to gastrointestinal hormones. Our work raises several questions relating to the conditions under which intestinal gluconeogenesis proceeds and may provide its metabolic benefits. It also leads to questions on the advantage conferred by its conservation through a process of natural selection. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Microbiota-Produced Succinate Improves Glucose Homeostasis via Intestinal Gluconeogenesis

    DEFF Research Database (Denmark)

    De Vadder, Filipe; Kovatcheva-Datchary, Petia; Zitoun, Carine

    2016-01-01

    Beneficial effects of dietary fiber on glucose and energy homeostasis have long been described, focusing mostly on the production of short-chain fatty acids by the gut commensal bacteria. However, bacterial fermentation of dietary fiber also produces large amounts of succinate and, to date......, no study has focused on the role of succinate on host metabolism. Here, we fed mice a fiber-rich diet and found that succinate was the most abundant carboxylic acid in the cecum. Dietary succinate was identified as a substrate for intestinal gluconeogenesis (IGN), a process that improves glucose...

  7. Serotonin 2C receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis.

    Science.gov (United States)

    Berglund, Eric D; Liu, Chen; Sohn, Jong-Woo; Liu, Tiemin; Kim, Mi Hwa; Lee, Charlotte E; Vianna, Claudia R; Williams, Kevin W; Xu, Yong; Elmquist, Joel K

    2013-12-01

    Energy and glucose homeostasis are regulated by central serotonin 2C receptors. These receptors are attractive pharmacological targets for the treatment of obesity; however, the identity of the serotonin 2C receptor-expressing neurons that mediate the effects of serotonin and serotonin 2C receptor agonists on energy and glucose homeostasis are unknown. Here, we show that mice lacking serotonin 2C receptors (Htr2c) specifically in pro-opiomelanocortin (POMC) neurons had normal body weight but developed glucoregulatory defects including hyperinsulinemia, hyperglucagonemia, hyperglycemia, and insulin resistance. Moreover, these mice did not show anorectic responses to serotonergic agents that suppress appetite and developed hyperphagia and obesity when they were fed a high-fat/high-sugar diet. A requirement of serotonin 2C receptors in POMC neurons for the maintenance of normal energy and glucose homeostasis was further demonstrated when Htr2c loss was induced in POMC neurons in adult mice using a tamoxifen-inducible POMC-cre system. These data demonstrate that serotonin 2C receptor-expressing POMC neurons are required to control energy and glucose homeostasis and implicate POMC neurons as the target for the effect of serotonin 2C receptor agonists on weight-loss induction and improved glycemic control.

  8. Bone morphogenetic proteins in inflammation, glucose homeostasis and adipose tissue energy metabolism

    DEFF Research Database (Denmark)

    Grgurevic, Lovorka; Christensen, Gitte Lund; Schulz, Tim J

    2016-01-01

    implicated in pancreas development as well as control of adult glucose homeostasis. Lastly, we review the recently recognized role of BMPs in brown adipose tissue formation and their consequences for energy expenditure and adiposity. In summary, BMPs play a pivotal role in metabolism beyond their role...... homeostasis (anaemia, hemochromatosis) and oxidative damage. The second and third parts of this review focus on BMPs in the development of metabolic pathologies such as type-2 diabetes mellitus and obesity. The pancreatic beta cells are the sole source of the hormone insulin and BMPs have recently been...

  9. Mathematical model of glucose-insulin homeostasis in healthy rats.

    Science.gov (United States)

    Lombarte, Mercedes; Lupo, Maela; Campetelli, German; Basualdo, Marta; Rigalli, Alfredo

    2013-10-01

    According to the World Health Organization there are over 220 million people in the world with diabetes and 3.4 million people died in 2004 as a consequence of this pathology. Development of an artificial pancreas would allow to restore control of blood glucose by coupling an infusion pump to a continuous glucose sensor in the blood. The design of such a device requires the development and application of mathematical models which represent the gluco-regulatory system. Models developed by other research groups describe very well the gluco-regulatory system but have a large number of mathematical equations and require complex methodologies for the estimation of its parameters. In this work we propose a mathematical model to study the homeostasis of glucose and insulin in healthy rats. The proposed model consists of three differential equations and 8 parameters that describe the variation of: blood glucose concentration, blood insulin concentration and amount of glucose in the intestine. All parameters were obtained by setting functions to the values of glucose and insulin in blood obtained after oral glucose administration. In vivo and in silico validations were performed. Additionally, a qualitative analysis has been done to verify the aforementioned model. We have shown that this model has a single, biologically consistent equilibrium point. This model is a first step in the development of a mathematical model for the type I diabetic rat. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Importance of the gut-brain axis in the control of glucose homeostasis.

    Science.gov (United States)

    Migrenne, Stéphanie; Marsollier, Nicolas; Cruciani-Guglielmacci, Céline; Magnan, Christophe

    2006-12-01

    Adult mammals finely match glucose production to glucose utilization, thus allowing glycaemia to be maintained in a physiological range of 0.8-1.2mg/dl whatever the energetic status of the mammal (i.e. fed or fasted, rested or exercised). To accomplish this, peripheral signals originating from the gut 'inform' the central nervous system, which in turn is able to monitor the status of both peripheral glucose stores and ongoing fuel availability. Indeed, both secretion and action of hormones regulating endogenous glucose production and utilization are regulated by the autonomic nervous system. These gut signals are either hormonal (e.g. glucagon-like peptide-1, ghrelin and cholecystokinine) or neuronal (e.g. afferent vagus nerve fibres). Recent data, combined with the development of incretin analogues for treatment of diabetes, highlight the importance of the gut-brain axis, especially glucagon-like peptide-1 and ghrelin, in the control of glucose homeostasis.

  11. A role of the adaptive immune system in glucose homeostasis.

    Science.gov (United States)

    Bronsart, Laura L; Contag, Christopher H

    2016-01-01

    The immune system, including the adaptive immune response, has recently been recognized as having a significant role in diet-induced insulin resistance. In this study, we aimed to determine if the adaptive immune system also functions in maintaining physiological glucose homeostasis in the absence of diet-induced disease. SCID mice and immunocompetent control animals were phenotypically assessed for variations in metabolic parameters and cytokine profiles. Additionally, the glucose tolerance of SCID and immunocompetent control animals was assessed following introduction of a high-fat diet. SCID mice on a normal chow diet were significantly insulin resistant relative to control animals despite having less fat mass. This was associated with a significant increase in the innate immunity-stimulating cytokines granulocyte colony-stimulating factor, monocyte chemoattractant protein 1 (MCP1), and MCP3. Additionally, the SCID mouse phenotype was exacerbated in response to a high-fat diet as evidenced by the further significant progression of glucose intolerance. These results support the notion that the adaptive immune system plays a fundamental biological role in glucose homeostasis, and that the absence of functional B and T cells results in disruption in the concentrations of various cytokines associated with macrophage proliferation and recruitment. Additionally, the absence of functional B and T cells is not protective against diet-induced pathology.

  12. Prion protein modulates glucose homeostasis by altering intracellular iron.

    Science.gov (United States)

    Ashok, Ajay; Singh, Neena

    2018-04-26

    The prion protein (PrP C ), a mainly neuronal protein, is known to modulate glucose homeostasis in mouse models. We explored the underlying mechanism in mouse models and the human pancreatic β-cell line 1.1B4. We report expression of PrP C on mouse pancreatic β-cells, where it promoted uptake of iron through divalent-metal-transporters. Accordingly, pancreatic iron stores in PrP knockout mice (PrP -/- ) were significantly lower than wild type (PrP +/+ ) controls. Silencing of PrP C in 1.1B4 cells resulted in significant depletion of intracellular (IC) iron, and remarkably, upregulation of glucose transporter GLUT2 and insulin. Iron overloading, on the other hand, resulted in downregulation of GLUT2 and insulin in a PrP C -dependent manner. Similar observations were noted in the brain, liver, and neuroretina of iron overloaded PrP +/+ but not PrP -/- mice, indicating PrP C -mediated modulation of insulin and glucose homeostasis through iron. Peripheral challenge with glucose and insulin revealed blunting of the response in iron-overloaded PrP +/+ relative to PrP -/- mice, suggesting that PrP C -mediated modulation of IC iron influences both secretion and sensitivity of peripheral organs to insulin. These observations have implications for Alzheimer's disease and diabetic retinopathy, known complications of type-2-diabetes associated with brain and ocular iron-dyshomeostasis.

  13. Glucose homeostasis in mice is transglutaminase 2 independent.

    Directory of Open Access Journals (Sweden)

    Siiri E Iismaa

    Full Text Available Transglutaminase type 2 (TG2 has been reported to be a candidate gene for maturity onset diabetes of the young (MODY because three different mutations that impair TG2 transamidase activity have been found in 3 families with MODY. TG2 null (TG2(-/- mice have been reported to be glucose intolerant and have impaired glucose-stimulated insulin secretion (GSIS. Here we rigorously evaluated the role of TG2 in glucose metabolism using independently generated murine models of genetic TG2 disruption, which show no compensatory enhanced expression of other TGs in pancreatic islets or other tissues. First, we subjected chow- or fat-fed congenic SV129 or C57BL/6 wild type (WT and TG2(-/- littermates, to oral glucose gavage. Blood glucose and serum insulin levels were similar for both genotypes. Pancreatic islets isolated from these animals and analysed in vitro for GSIS and cholinergic potentiation of GSIS, showed no significant difference between genotypes. Results from intraperitoneal glucose tolerance tests (GTTs and insulin tolerance tests (ITTs were similar for both genotypes. Second, we directly investigated the role of TG2 transamidase activity in insulin secretion using a coisogenic model that expresses a mutant form of TG2 (TG2(R579A, which is constitutively active for transamidase activity. Intraperitoneal GTTs and ITTs revealed no significant differences between WT and TG2(R579A/R579A mice. Given that neither deletion nor constitutive activation of TG2 transamidase activity altered basal responses, or responses to a glucose or insulin challenge, our data indicate that glucose homeostasis in mice is TG2 independent, and question a link between TG2 and diabetes.

  14. Central insulin action in energy and glucose homeostasis.

    Science.gov (United States)

    Plum, Leona; Belgardt, Bengt F; Brüning, Jens C

    2006-07-01

    Insulin has pleiotropic biological effects in virtually all tissues. However, the relevance of insulin signaling in peripheral tissues has been studied far more extensively than its role in the brain. An evolving body of evidence indicates that in the brain, insulin is involved in multiple regulatory mechanisms including neuronal survival, learning, and memory, as well as in regulation of energy homeostasis and reproductive endocrinology. Here we review insulin's role as a central homeostatic signal with regard to energy and glucose homeostasis and discuss the mechanisms by which insulin communicates information about the body's energy status to the brain. Particular emphasis is placed on the controversial current debate about the similarities and differences between hypothalamic insulin and leptin signaling at the molecular level.

  15. Effects of Taurine Supplementation on Neuronal Excitability and Glucose Homeostasis.

    Science.gov (United States)

    El Idrissi, Abdeslem; El Hilali, Fatiha; Rotondo, Salvatore; Sidime, Francoise

    2017-01-01

    In this study we examined the role of chronic taurine supplementation on plasma glucose homeostasis and brain excitability through activation of the insulin receptor. FVB/NJ male mice were supplemented with taurine in drinking water (0.05% w/v) for 4 weeks and subjected to a glucose tolerance test (7.5 mg/kg BW) after 12 h fasting. We found that taurine-fed mice were slightly hypoglycemic prior to glucose injection and showed significantly reduced plasma glucose at 30 and 60 min post-glucose injection when compared to control mice. Previously, we reported that taurine supplementation induces biochemical changes that target the GABAergic system. Those studies show that taurine-fed mice are hyperexcitable, have reduced GABA A receptors expression and increased GAD and somatostatin expression in the brain. In this study, we found that taurine-fed mice had a significant increase in insulin receptor (IR) immuno-reactivity in the pancreas and all brain regions examined. At the mRNA level, we found that the IR showed differential regional expression. Surprisingly, we found that neurons express the gene for insulin and that taurine had a significant role in regulating insulin gene expression. We propose that increased insulin production and secretion in taurine-fed mice cause an increase activation of the central IR and may be partially responsible for the increased neuronal excitability observed in taurine supplemented mice. Furthermore, the high levels of neuronal insulin expression and its regulation by taurine implicates taurine in the regulation of metabolic homeostasis.

  16. Ventromedial hypothalamic glucose sensing and glucose homeostasis vary throughout the estrous cycle.

    Science.gov (United States)

    Santiago, Ammy M; Clegg, Deborah J; Routh, Vanessa H

    2016-12-01

    17β-Estradiol (17βE) regulates glucose homeostasis in part by centrally mediated mechanisms. In female rodents, the influence of the ovarian cycle on hypoglycemia counterregulation and glucose tolerance is unclear. We found previously that in prepubertal females, 17βE modulates glucose sensing in nonadapting glucose-inhibited (GI) and adapting GI (AdGI) neurons within the ventrolateral portion of the ventromedial nucleus (VL-VMN). Nonadapting GI neurons persistently decrease their activity as glucose increases while AdGI neurons transiently respond to a glucose increase. To begin to understand if endogenous fluctuations in estrogen levels across the estrous cycle impact hypothalamic glucose sensing and glucose homeostasis, we assessed whether hypoglycemia counterregulation and glucose tolerance differed across the phases of the estrous cycle. We hypothesized that the response to insulin-induced hypoglycemia (IIH) and/or glucose tolerance would vary throughout the estrous cycle according to changes in 17βE availability. Moreover, that these changes would correlate with estrous-dependent changes in the glucose sensitivity of VL-VMN glucose-sensing neurons (GSNs). These hypotheses were tested in female mice by measuring the response to IIH, glucose tolerance and the glucose sensitivity of VL-VMN GSNs during each phase of the estrous cycle. Furthermore, a physiological brain concentration of 17βE seen during proestrus was acutely applied to brain slices isolated on the day of diestrous and the response to low glucose in VL-VMN GSNs was assayed. The response to IIH was strongest during diestrous. The response of nonadapting GI and AdGI neurons to a glucose decrease from 2.5 to 0.5mM also peaked during diestrous; an effect which was blunted by the addition of 17βE. In contrast, the glucose sensitivity of the subpopulation of GSNs which are excited by glucose (GE) was not affected by estrous phase or exogenous 17βE application. These data suggest that physiological

  17. Ventromedial hypothalamic glucose sensing and glucose homeostasis vary throughout the estrous cycle

    Science.gov (United States)

    Santiago, Ammy M.; Clegg, Deborah J.; Routh, Vanessa H.

    2016-01-01

    Objective 17β-Estradiol (17βE) regulates glucose homeostasis in part by centrally mediated mechanisms. In female rodents, the influence of the ovarian cycle on hypoglycemia counterregulation and glucose tolerance is unclear. We found previously that in prepubertal females, 17βE modulates glucose sensing in nonadapting glucose-inhibited (GI) and adapting GI (AdGI) neurons within the ventrolateral portion of the ventromedial nucleus (VL-VMN). Nonadapting GI neurons persistently decrease their activity as glucose increases while AdGI neurons transiently respond to a glucose increase. To begin to understand if endogenous fluctuations in estrogen levels across the estrous cycle impact hypothalamic glucose sensing and glucose homeostasis, we assessed whether hypoglycemia counterregulation and glucose tolerance differed across the phases of the estrous cycle. We hypothesized that the response to insulin-induced hypoglycemia (IIH) and/or glucose tolerance would vary throughout the estrous cycle according to changes in 17βE availability. Moreover, that these changes would correlate with estrous-dependent changes in the glucose sensitivity of VL-VMN glucose-sensing neurons (GSNs). Methods These hypotheses were tested in female mice by measuring the response to IIH, glucose tolerance and the glucose sensitivity of VL-VMN GSNs during each phase of the estrous cycle. Furthermore, a physiological brain concentration of 17βE seen during proestrus was acutely applied to brain slices isolated on the day of diestrous and the response to low glucose in VL-VMN GSNs was assayed. Results The response to IIH was strongest during diestrous. The response of nonadapting GI and AdGI neurons to a glucose decrease from 2.5 to 0.5mM also peaked during diestrous; an effect which was blunted by the addition of 17βE. In contrast, the glucose sensitivity of the subpopulation of GSNs which are excited by glucose (GE) was not affected by estrous phase or exogenous 17βE application. Conclusion

  18. Glucose is necessary to maintain neurotransmitter homeostasis during synaptic activity in cultured glutamatergic neurons.

    Science.gov (United States)

    Bak, Lasse K; Schousboe, Arne; Sonnewald, Ursula; Waagepetersen, Helle S

    2006-10-01

    Glucose is the primary energy substrate for the adult mammalian brain. However, lactate produced within the brain might be able to serve this purpose in neurons. In the present study, the relative significance of glucose and lactate as substrates to maintain neurotransmitter homeostasis was investigated. Cultured cerebellar (primarily glutamatergic) neurons were superfused in medium containing [U-13C]glucose (2.5 mmol/L) and lactate (1 or 5 mmol/L) or glucose (2.5 mmol/L) and [U-13C]lactate (1 mmol/L), and exposed to pulses of N-methyl-D-aspartate (300 micromol/L), leading to synaptic activity including vesicular release. The incorporation of 13C label into intracellular lactate, alanine, succinate, glutamate, and aspartate was determined by mass spectrometry. The metabolism of [U-13C]lactate under non-depolarizing conditions was high compared with that of [U-13C]glucose; however, it decreased significantly during induced depolarization. In contrast, at both concentrations of extracellular lactate, the metabolism of [U-13C]glucose was increased during neuronal depolarization. The role of glucose and lactate as energy substrates during vesicular release as well as transporter-mediated influx and efflux of glutamate was examined using preloaded D-[3H]aspartate as a glutamate tracer and DL-threo-beta-benzyloxyaspartate to inhibit glutamate transporters. The results suggest that glucose is essential to prevent depolarization-induced reversal of the transporter (efflux), whereas vesicular release was unaffected by the choice of substrate. In conclusion, the present study shows that glucose is a necessary substrate to maintain neurotransmitter homeostasis during synaptic activity and that synaptic activity does not induce an upregulation of lactate metabolism in glutamatergic neurons.

  19. The role of biological clock in glucose homeostasis 

    Directory of Open Access Journals (Sweden)

    Piotr Chrościcki

    2013-06-01

    Full Text Available The mechanism of the biological clock is based on a rhythmic expression of clock genes and clock-controlled genes. As a result of their transcripto-translational associations, endogenous rhythms in the synthesis of key proteins of various physiological and metabolic processes are created. The major timekeeping mechanism for these rhythms exists in the central nervous system. The master circadian clock, localized in suprachiasmatic nucleus (SCN, regulates multiple metabolic pathways, while feeding behavior and metabolite availability can in turn regulate the circadian clock. It is also suggested that in the brain there is a food entrainable oscillator (FEO or oscillators, resulting in activation of both food anticipatory activity and hormone secretion that control digestion processes. Moreover, most cells and tissues express autonomous clocks. Maintenance of the glucose homeostasis is particularly important for the proper function of the body, as this sugar is the main source of energy for the brain, retina, erythrocytes and skeletal muscles. Thus, glucose production and utilization are synchronized in time. The hypothalamic excited orexin neurons control energy balance of organism and modulate the glucose production and utilization. Deficiency of orexin action results in narcolepsy and weight gain, whereas glucose and amino acids can affect activity of the orexin cells. Large-scale genetic studies in rodents and humans provide evidence for the involvement of disrupted clock gene expression rhythms in the pathogenesis of obesity and type 2 diabetes. In general, the current lifestyle of the developed modern societies disturbs the action of biological clock. 

  20. Regulation of glucose homeostasis by KSR1 and MARK2.

    Directory of Open Access Journals (Sweden)

    Paula J Klutho

    Full Text Available Protein scaffolds control the intensity and duration of signaling and dictate the specificity of signaling through MAP kinase pathways. KSR1 is a molecular scaffold of the Raf/MEK/ERK MAP kinase cascade that regulates the intensity and duration of ERK activation. Relative to wild-type mice, ksr1⁻/⁻ mice are modestly glucose intolerant, but show a normal response to exogenous insulin. However, ksr1⁻/⁻ mice also demonstrate a three-fold increase in serum insulin levels in response to a glucose challenge, suggesting a role for KSR1 in insulin secretion. The kinase MARK2 is closely related to C-TAK1, a known regulator of KSR1. Mice lacking MARK2 have an increased rate of glucose disposal in response to exogenous insulin, increased glucose tolerance, and are resistant to diet-induced obesity. mark2⁻/⁻ksr1⁻/⁻ (DKO mice were compared to wild type, mark2⁻/⁻, and ksr1⁻/⁻ mice for their ability to regulate glucose homeostasis. Here we show that disruption of KSR1 in mark2⁻/⁻ mice reverses the increased sensitivity to exogenous insulin resulting from MARK2 deletion. DKO mice respond to exogenous insulin similarly to wild type and ksr1⁻/⁻ mice. These data suggest a model whereby MARK2 negatively regulates insulin sensitivity in peripheral tissue through inhibition of KSR1. Consistent with this model, we found that MARK2 binds and phosphorylates KSR1 on Ser392. Phosphorylation of Ser392 is a critical regulator of KSR1 stability, subcellular location, and ERK activation. These data reveal an unexpected role for the molecular scaffold KSR1 in insulin-regulated glucose metabolism.

  1. Sleep duration and sleep quality are associated differently with alterations of glucose homeostasis.

    Science.gov (United States)

    Byberg, S; Hansen, A-L S; Christensen, D L; Vistisen, D; Aadahl, M; Linneberg, A; Witte, D R

    2012-09-01

    Studies suggest that inadequate sleep duration and poor sleep quality increase the risk of impaired glucose regulation and diabetes. However, associations with specific markers of glucose homeostasis are less well explained. The objective of this study was to explore possible associations of sleep duration and sleep quality with markers of glucose homeostasis and glucose tolerance status in a healthy population-based study sample. The study comprised 771 participants from the Danish, population-based cross-sectional 'Health2008' study. Sleep duration and sleep quality were measured by self-report. Markers of glucose homeostasis were derived from a 3-point oral glucose tolerance test and included fasting plasma glucose, 2-h plasma glucose, HbA(1c), two measures of insulin sensitivity (the insulin sensitivity index(0,120) and homeostasis model assessment of insulin sensitivity), the homeostasis model assessment of β-cell function and glucose tolerance status. Associations of sleep duration and sleep quality with markers of glucose homeostasis and tolerance were analysed by multiple linear and logistic regression. A 1-h increment in sleep duration was associated with a 0.3 mmol/mol (0.3%) decrement in HbA(1c) and a 25% reduction in the risk of having impaired glucose regulation. Further, a 1-point increment in sleep quality was associated with a 2% increase in both the insulin sensitivity index(0,120) and homeostasis model assessment of insulin sensitivity, as well as a 1% decrease in homeostasis model assessment of β-cell function. In the present study, shorter sleep duration was mainly associated with later alterations in glucose homeostasis, whereas poorer sleep quality was mainly associated with earlier alterations in glucose homeostasis. Thus, adopting healthy sleep habits may benefit glucose metabolism in healthy populations. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

  2. Sleep duration and sleep quality are associated differently with alterations of glucose homeostasis

    DEFF Research Database (Denmark)

    Byberg, Stine; Hansen, Anne-Louise Smidt; Christensen, Dirk Lund

    2012-01-01

    Abstract Aims  Studies suggest that inadequate sleep duration and poor sleep quality increase the risk of impaired glucose regulation and diabetes. However, associations with specific markers of glucose homeostasis are less well explained. The objective of this study was to explore possible...... associations of sleep duration and sleep quality with markers of glucose homeostasis and glucose tolerance status in a healthy population-based study sample. Methods  The study comprised 771 participants from the Danish, population-based cross-sectional ‘Health2008’ study. Sleep duration and sleep quality were...... measured by self-report. Markers of glucose homeostasis were derived from a 3-point oral glucose tolerance test and included fasting plasma glucose, 2-h plasma glucose, HbA1c, two measures of insulin sensitivity (the insulin sensitivity index0,120 and homeostasis model assessment of insulin sensitivity...

  3. Common genetic determinants of glucose homeostasis in healthy children

    DEFF Research Database (Denmark)

    Kelliny, Clara; Ekelund, Ulf; Andersen, Lars Bo

    2009-01-01

    ) were genotyped in 2,025 healthy European children aged 9-11 and 14-16 years. Associations with fasting glucose, insulin, homeostasis model assessment (HOMA)-insulin resistance (IR) and HOMA-B were investigated along with those observed for type 2 diabetes variants available in this study (CDKN2A/B, IGF....... A similar but weaker trend was observed for GCK (0.028 [-0.006 to 0.06] mmol/l, P = 0.11). All three variants were associated with lower beta-cell function (HOMA-B P = 9.38 x 10(-5), 0.004, and 0.04, respectively). SLC30A8 (rs13266634) was the only type 2 diabetes variant associated with higher fasting...

  4. Revisiting "Vegetables" to combat modern epidemic of imbalanced glucose homeostasis.

    Science.gov (United States)

    Tiwari, Ashok Kumar

    2014-04-01

    Vegetables have been part of human food since prehistoric times and are considered nutritionally necessary and good for health. Vegetables are rich natural resource of biological antioxidants and possess capabilities of maintaining glucose homeostasis. When taken before starch-rich diet, juice also of vegetables such as ridge gourd, bottle gourd, ash gourd, chayote and juice of leaves of vegetables such as radish, Indian Dill, ajwain, tropical green amaranth, and bladder dock are reported to arrest significantly the rise in postprandial blood glucose level. Juice of vegetables such as ash gourd, squash gourd, and tropical green amaranth leaves are observed to tone-down sweet-beverages such as sucrose, fructose, and glucose-induced postprandial glycemic excursion. On the other hand, juice of egg-plant and juice of leaves of Ceylon spinach, Joyweed, and palak are reported to augment starch-induced postprandial glycemic excursion; and juice of leaves of Ceylon spinach, Joyweed, and radish supplement to the glucose-induced postprandial glycemia. Vegetables possess multifaceted antihyperglycemic activities such as inhibition of pancreatic α-amylase and intestinal α-glucosidase, inhibition of protein-tyrosine phosphatase 1β in liver and skeletal muscles, and insulin mimetic and secretagogue activities. Furthermore, they are also reported to influence polyol pathway in favor of reducing development of oxidative stress, and consequently the development of diabetic complications. In the wake of emergence of modern maladaptive diet-induced hyperglycemic epidemic therefore, vegetables may offer cost-effective dietary regimen to control diet-induced glycemic over load and future development of diabetes mellitus. However, for vegetables have been reported to do both, mitigate as well as supplement to the diet-induced postprandial glycemic load, care is required in selection of vegetables when considered as medicament.

  5. Exenatide Regulates Cerebral Glucose Metabolism in Brain Areas Associated With Glucose Homeostasis and Reward System.

    Science.gov (United States)

    Daniele, Giuseppe; Iozzo, Patricia; Molina-Carrion, Marjorie; Lancaster, Jack; Ciociaro, Demetrio; Cersosimo, Eugenio; Tripathy, Devjit; Triplitt, Curtis; Fox, Peter; Musi, Nicolas; DeFronzo, Ralph; Gastaldelli, Amalia

    2015-10-01

    Glucagon-like peptide 1 receptors (GLP-1Rs) have been found in the brain, but whether GLP-1R agonists (GLP-1RAs) influence brain glucose metabolism is currently unknown. The study aim was to evaluate the effects of a single injection of the GLP-1RA exenatide on cerebral and peripheral glucose metabolism in response to a glucose load. In 15 male subjects with HbA1c of 5.7 ± 0.1%, fasting glucose of 114 ± 3 mg/dL, and 2-h glucose of 177 ± 11 mg/dL, exenatide (5 μg) or placebo was injected in double-blind, randomized fashion subcutaneously 30 min before an oral glucose tolerance test (OGTT). The cerebral glucose metabolic rate (CMRglu) was measured by positron emission tomography after an injection of [(18)F]2-fluoro-2-deoxy-d-glucose before the OGTT, and the rate of glucose absorption (RaO) and disposal was assessed using stable isotope tracers. Exenatide reduced RaO0-60 min (4.6 ± 1.4 vs. 13.1 ± 1.7 μmol/min ⋅ kg) and decreased the rise in mean glucose0-60 min (107 ± 6 vs. 138 ± 8 mg/dL) and insulin0-60 min (17.3 ± 3.1 vs. 24.7 ± 3.8 mU/L). Exenatide increased CMRglu in areas of the brain related to glucose homeostasis, appetite, and food reward, despite lower plasma insulin concentrations, but reduced glucose uptake in the hypothalamus. Decreased RaO0-60 min after exenatide was inversely correlated to CMRglu. In conclusion, these results demonstrate, for the first time in man, a major effect of a GLP-1RA on regulation of brain glucose metabolism in the absorptive state. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  6. Setting sail for glucose homeostasis with the AKAP150-PP2B-anchor.

    Science.gov (United States)

    Teo, Adrian Kee Keong; Kulkarni, Rohit N

    2012-10-17

    Glucose-stimulated insulin secretion, controlled by multiple protein phosphorylation events, is critical for the regulation of glucose homeostasis. Protein kinase A (PKA) is known to play a role in β cell physiology, but the role of its anchoring protein is not fully understood. Hinke et al (2012) illustrate the significance of A-kinase anchoring protein 150 in tethering protein phosphatase 2B to mediate nutrient-stimulated insulin secretion and thus modulate glucose homeostasis.

  7. Hormones and the Autonomic Nervous System are Involved in Suprachiasmatic Nucleus Modulation of Glucose Homeostasis

    NARCIS (Netherlands)

    Ruiter, M.; Buijs, R.M.; Kalsbeek, A.

    2006-01-01

    Glucose is one of the most important energy sources for the body in general, and the brain in particular. It is essential for survival to keep glucose levels within strict boundaries. Acute disturbances of glucose homeostasis are rapidly corrected by hormonal and neuronal mechanisms. Furthermore,

  8. Hormones and the autonomic nervous system are involved in suprachiasmatic nucleus modulation of glucose homeostasis

    NARCIS (Netherlands)

    Ruiter, Marieke; Buijs, Ruud M.; Kalsbeek, Andries

    2006-01-01

    Glucose is one of the most important energy sources for the body in general, and the brain in particular. It is essential for survival to keep glucose levels within strict boundaries. Acute disturbances of glucose homeostasis are rapidly corrected by hormonal and neuronal mechanisms. Furthermore,

  9. The effect of hepatectomy on glucose homeostasis in pig and in man

    DEFF Research Database (Denmark)

    Lauritsen, Torsten Leif Bunk; Grunnet, Niels; Rasmussen, Allan

    2002-01-01

    and muscle) to the glucose homeostasis in the anhepatic pig and in man during the anhepatic phase of human liver transplantations. METHODS: Blood glucose and lactate were monitored in the anhepatic phase in 46 patients undergoing liver transplantation. Arterial-venous differences of lactate, glucose...

  10. Mechanisms and significance of brain glucose signaling in energy balance, glucose homeostasis, and food-induced reward.

    Science.gov (United States)

    Devarakonda, Kavya; Mobbs, Charles V

    2016-12-15

    The concept that hypothalamic glucose signaling plays an important role in regulating energy balance, e.g., as instantiated in the so-called "glucostat" hypothesis, is one of the oldest in the field of metabolism. However the mechanisms by which neurons in the hypothalamus sense glucose, and the function of glucose signaling in the brain, has been difficult to establish. Nevertheless recent studies probing mechanisms of glucose signaling have also strongly supported a role for glucose signaling in regulating energy balance, glucose homeostasis, and food-induced reward. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Preoperative octreotide therapy and surgery in acromegaly: associations between glucose homeostasis and treatment response.

    Science.gov (United States)

    Helseth, R; Carlsen, S M; Bollerslev, J; Svartberg, J; Øksnes, M; Skeie, S; Fougner, S L

    2016-02-01

    In acromegaly, high GH/IGF-1 levels associate with abnormal glucose metabolism. Somatostatin analogs (SSAs) reduce GH and IGF-1 but inhibit insulin secretion. We studied glucose homeostasis in de novo patients with acromegaly and changes in glucose metabolism after treatment with SSA and surgery. In this post hoc analysis from a randomized controlled trial, 55 de novo patients with acromegaly, not using antidiabetic medication, were included. Before surgery, 26 patients received SSAs for 6 months. HbA1c, fasting glucose, and oral glucose tolerance test were performed at baseline, after SSA pretreatment and at 3 months postoperative. Area under curve of glucose (AUC-G) was calculated. Glucose homeostasis was compared to baseline levels of GH and IGF-1, change after SSA pretreatment, and remission both after SSA pretreatment and 3 months postoperative. In de novo patients, IGF-1/GH levels did not associate with baseline glucose parameters. After SSA pretreatment, changes in GH/IGF-1 correlated positively to change in HbA1c levels (both p acromegaly, disease activity did not correlate with glucose homeostasis. Surgical treatment of acromegaly improved glucose metabolism in both cured and not cured patients, while SSA pretreatment led to deterioration in glucose homeostasis in patients not achieving biochemical control.

  12. Role of Snf3 in glucose homeostasis of Saccharomyces cerevisiae (review)

    DEFF Research Database (Denmark)

    Kielland-Brandt, Morten

    signal pathways in directions opposite to those caused by extracellular nutrients (6,7), a phenomenon predicted to contribute to intracellular nutrient homeostasis. Although significant, the influence of intracellular leucine on signaling from Ssy1 is relatively modest (6), whereas the conditions...... with enhanced intracellular glucose concentrations (7) caused a strong decrease in signaling from Snf3, suggesting an important role of Snf3 in intracellular glucose homeostasis. Strategies for studies of this role will be discussed....

  13. Acute activation of GLP-1-expressing neurons promotes glucose homeostasis and insulin sensitivity

    OpenAIRE

    Xuemei Shi; Shaji Chacko; Feng Li; Depei Li; Douglas Burrin; Lawrence Chan; Xinfu Guan

    2017-01-01

    Objective: Glucagon-like peptides are co-released from enteroendocrine L cells in the gut and preproglucagon (PPG) neurons in the brainstem. PPG-derived GLP-1/2 are probably key neuroendocrine signals for the control of energy balance and glucose homeostasis. The objective of this study was to determine whether activation of PPG neurons per se modulates glucose homeostasis and insulin sensitivity in vivo. Methods: We generated glucagon (Gcg) promoter-driven Cre transgenic mice and injected...

  14. Impact of low dose prenatal ethanol exposure on glucose homeostasis in Sprague-Dawley rats aged up to eight months.

    Directory of Open Access Journals (Sweden)

    Megan E Probyn

    Full Text Available Excessive exposure to alcohol prenatally has a myriad of detrimental effects on the health and well-being of the offspring. It is unknown whether chronic low-moderate exposure of alcohol prenatally has similar and lasting effects on the adult offspring's health. Using our recently developed Sprague-Dawley rat model of 6% chronic prenatal ethanol exposure, this study aimed to determine if this modest level of exposure adversely affects glucose homeostasis in male and female offspring aged up to eight months. Plasma glucose concentrations were measured in late fetal and postnatal life. The pancreas of 30 day old offspring was analysed for β-cell mass. Glucose handling and insulin action was measured at four months using an intraperitoneal glucose tolerance test and insulin challenge, respectively. Body composition and metabolic gene expression were measured at eight months. Despite normoglycaemia in ethanol consuming dams, ethanol-exposed fetuses were hypoglycaemic at embryonic day 20. Ethanol-exposed offspring were normoglycaemic and normoinsulinaemic under basal fasting conditions and had normal pancreatic β-cell mass at postnatal day 30. However, during a glucose tolerance test, male ethanol-exposed offspring were hyperinsulinaemic with increased first phase insulin secretion. Female ethanol-exposed offspring displayed enhanced glucose clearance during an insulin challenge. Body composition and hepatic, muscle and adipose tissue metabolic gene expression levels at eight months were not altered by prenatal ethanol exposure. Low-moderate chronic prenatal ethanol exposure has subtle, sex specific effects on glucose homeostasis in the young adult rat. As aging is associated with glucose dysregulation, further studies will clarify the long lasting effects of prenatal ethanol exposure.

  15. Central insulin and leptin-mediated autonomic control of glucose homeostasis

    OpenAIRE

    Marino, Joseph S.; Xu, Yong; Hill, Jennifer W.

    2011-01-01

    Largely as a result of rising obesity rates, the incidence of type 2 diabetes is escalating rapidly. Type 2 diabetes results from multi-organ dysfunctional glucose metabolism. Recent publications have highlighted hypothalamic insulin- and adipokine-sensing as a major determinant of peripheral glucose and insulin responsiveness. The preponderance of evidence indicates that the brain is the master regulator of glucose homeostasis, and that hypothalamic insulin and leptin signaling in particular...

  16. CREBH Maintains Circadian Glucose Homeostasis by Regulating Hepatic Glycogenolysis and Gluconeogenesis.

    Science.gov (United States)

    Kim, Hyunbae; Zheng, Ze; Walker, Paul D; Kapatos, Gregory; Zhang, Kezhong

    2017-07-15

    Cyclic AMP-responsive element binding protein, hepatocyte specific (CREBH), is a liver-enriched, endoplasmic reticulum-tethered transcription factor known to regulate the hepatic acute-phase response and lipid homeostasis. In this study, we demonstrate that CREBH functions as a circadian transcriptional regulator that plays major roles in maintaining glucose homeostasis. The proteolytic cleavage and posttranslational acetylation modification of CREBH are regulated by the circadian clock. Functionally, CREBH is required in order to maintain circadian homeostasis of hepatic glycogen storage and blood glucose levels. CREBH regulates the rhythmic expression of the genes encoding the rate-limiting enzymes for glycogenolysis and gluconeogenesis, including liver glycogen phosphorylase (PYGL), phosphoenolpyruvate carboxykinase 1 (PCK1), and the glucose-6-phosphatase catalytic subunit (G6PC). CREBH interacts with peroxisome proliferator-activated receptor α (PPARα) to synergize its transcriptional activities in hepatic gluconeogenesis. The acetylation of CREBH at lysine residue 294 controls CREBH-PPARα interaction and synergy in regulating hepatic glucose metabolism in mice. CREBH deficiency leads to reduced blood glucose levels but increases hepatic glycogen levels during the daytime or upon fasting. In summary, our studies revealed that CREBH functions as a key metabolic regulator that controls glucose homeostasis across the circadian cycle or under metabolic stress. Copyright © 2017 American Society for Microbiology.

  17. Influence of Amino Acids in Dairy Products on Glucose Homeostasis: The Clinical Evidence.

    Science.gov (United States)

    Chartrand, Dominic; Da Silva, Marine S; Julien, Pierre; Rudkowska, Iwona

    2017-06-01

    Dairy products have been hypothesized to protect against type 2 diabetes because of their high content of whey proteins, rich in branched-chain amino acids (BCAAs) - leucine, isoleucine and valine - and lysine, which may decrease postprandial glucose responses and stimulate insulin secretion. Paradoxically, epidemiologic studies also show that higher levels of plasma BCAAs have been linked to insulin resistance and type 2 diabetes. Therefore, the objective was to review the recent clinical evidence concerning the intake of amino acids found in dairy proteins so as to determine their impact on glucose homeostasis in healthy persons and in those with prediabetes and type 2 diabetes. Clinical studies have reported that the major dairy amino acids, namely, leucine, isoleucine, glutamine, phenylalanine, proline and lysine, have beneficial effects on glucose homeostasis. Yet the reported doses of amino acids investigated are too elevated to be reached through adequate dairy product intake. The minor dairy amino acids, arginine and glycine, may improve glucose homeostasis by improving other risk factors for type 2 diabetes. Further, the combination of amino acids may also improve glucose-related outcomes, suggesting additive or synergistic effects. Nevertheless, additional long-term studies in individuals with prediabetes and type 2 diabetes are needed to ascertain the benefits for glucose homeostasis of amino acids found in dairy foods. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

  18. Gastrointestinal Transit Time, Glucose Homeostasis and Metabolic Health: Modulation by Dietary Fibers.

    Science.gov (United States)

    Müller, Mattea; Canfora, Emanuel E; Blaak, Ellen E

    2018-02-28

    Gastrointestinal transit time may be an important determinant of glucose homeostasis and metabolic health through effects on nutrient absorption and microbial composition, among other mechanisms. Modulation of gastrointestinal transit may be one of the mechanisms underlying the beneficial health effects of dietary fibers. These effects include improved glucose homeostasis and a reduced risk of developing metabolic diseases such as obesity and type 2 diabetes mellitus. In this review, we first discuss the regulation of gastric emptying rate, small intestinal transit and colonic transit as well as their relation to glucose homeostasis and metabolic health. Subsequently, we briefly address the reported health effects of different dietary fibers and discuss to what extent the fiber-induced health benefits may be mediated through modulation of gastrointestinal transit.

  19. Rictor/mTORC2 facilitates central regulation of energy and glucose homeostasis

    OpenAIRE

    Kocalis, Heidi E.; Hagan, Scott L.; George, Leena; Turney, Maxine K.; Siuta, Michael A.; Laryea, Gloria N.; Morris, Lindsey C.; Muglia, Louis J.; Printz, Richard L.; Stanwood, Gregg D.; Niswender, Kevin D.

    2014-01-01

    Insulin signaling in the central nervous system (CNS) regulates energy balance and peripheral glucose homeostasis. Rictor is a key regulatory/structural subunit of the mTORC2 complex and is required for hydrophobic motif site phosphorylation of Akt at serine 473. To examine the contribution of neuronal Rictor/mTORC2 signaling to CNS regulation of energy and glucose homeostasis, we utilized Cre-LoxP technology to generate mice lacking Rictor in all neurons, or in either POMC or AgRP expressing...

  20. Acute activation of GLP-1-expressing neurons promotes glucose homeostasis and insulin sensitivity.

    Science.gov (United States)

    Shi, Xuemei; Chacko, Shaji; Li, Feng; Li, Depei; Burrin, Douglas; Chan, Lawrence; Guan, Xinfu

    2017-11-01

    Glucagon-like peptides are co-released from enteroendocrine L cells in the gut and preproglucagon (PPG) neurons in the brainstem. PPG-derived GLP-1/2 are probably key neuroendocrine signals for the control of energy balance and glucose homeostasis. The objective of this study was to determine whether activation of PPG neurons per se modulates glucose homeostasis and insulin sensitivity in vivo. We generated glucagon (Gcg) promoter-driven Cre transgenic mice and injected excitatory hM3Dq-mCherry AAV into their brainstem NTS. We characterized the metabolic impact of PPG neuron activation on glucose homeostasis and insulin sensitivity using stable isotopic tracers coupled with hyperinsulinemic euglycemic clamp. We showed that after ip injection of clozapine N-oxide, Gcg-Cre lean mice transduced with hM3Dq in the brainstem NTS downregulated basal endogenous glucose production and enhanced glucose tolerance following ip glucose tolerance test. Moreover, acute activation of PPG neurons NTS enhanced whole-body insulin sensitivity as indicated by increased glucose infusion rate as well as augmented insulin-suppression of endogenous glucose production and gluconeogenesis. In contrast, insulin-stimulation of glucose disposal was not altered significantly. We conclude that acute activation of PPG neurons in the brainstem reduces basal glucose production, enhances intraperitoneal glucose tolerance, and augments hepatic insulin sensitivity, suggesting an important physiological role of PPG neurons-mediated circuitry in promoting glycemic control and insulin sensitivity. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

  1. Glucose Homeostasis Variables in Pregnancy versus Maternal and Infant Body Composition

    Directory of Open Access Journals (Sweden)

    Pontus Henriksson

    2015-07-01

    Full Text Available Intrauterine factors influence infant size and body composition but the mechanisms involved are to a large extent unknown. We studied relationships between the body composition of pregnant women and variables related to their glucose homeostasis, i.e., glucose, HOMA-IR (homeostasis model assessment-insulin resistance, hemoglobin A1c and IGFBP-1 (insulin-like growth factor binding protein-1, and related these variables to the body composition of their infants. Body composition of 209 women in gestational week 32 and of their healthy, singleton and full-term one-week-old infants was measured using air displacement plethysmography. Glucose homeostasis variables were assessed in gestational week 32. HOMA-IR was positively related to fat mass index and fat mass (r2 = 0.32, p < 0.001 of the women. Maternal glucose and HOMA-IR values were positively (p ≤ 0.006 associated, while IGFBP-1was negatively (p = 0.001 associated, with infant fat mass. HOMA-IR was positively associated with fat mass of daughters (p < 0.001, but not of sons (p = 0.65 (Sex-interaction: p = 0.042. In conclusion, glucose homeostasis variables of pregnant women are related to their own body composition and to that of their infants. The results suggest that a previously identified relationship between fat mass of mothers and daughters is mediated by maternal insulin resistance.

  2. Bayesian model discrimination for glucose-insulin homeostasis

    DEFF Research Database (Denmark)

    Andersen, Kim Emil; Brooks, Stephen P.; Højbjerre, Malene

    In this paper we analyse a set of experimental data on a number of healthy and diabetic patients and discuss a variety of models for describing the physiological processes involved in glucose absorption and insulin secretion within the human body. We adopt a Bayesian approach which facilitates...... as parameter uncertainty. Markov chain Monte Carlo methods are used, combining Metropolis Hastings, reversible jump and simulated tempering updates to provide rapidly mixing chains so as to provide robust inference. We demonstrate the methodology for both healthy and type II diabetic populations concluding...... that whilst both populations are well modelled by a common insulin model, their glucose dynamics differ considerably....

  3. Central insulin and leptin-mediated autonomic control of glucose homeostasis.

    Science.gov (United States)

    Marino, Joseph S; Xu, Yong; Hill, Jennifer W

    2011-07-01

    Largely as a result of rising obesity rates, the incidence of type 2 diabetes is escalating rapidly. Type 2 diabetes results from multi-organ dysfunctional glucose metabolism. Recent publications have highlighted hypothalamic insulin- and adipokine-sensing as a major determinant of peripheral glucose and insulin responsiveness. The preponderance of evidence indicates that the brain is the master regulator of glucose homeostasis, and that hypothalamic insulin and leptin signaling in particular play a crucial role in the development of insulin resistance. This review discusses the neuronal crosstalk between the hypothalamus, autonomic nervous system, and tissues associated with the pathogenesis of type 2 diabetes, and how hypothalamic insulin and leptin signaling are integral to maintaining normal glucose homeostasis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Chronic Sleep Disturbance Impairs Glucose Homeostasis in Rats

    NARCIS (Netherlands)

    Barf, R. Paulien; Meerlo, Peter; Scheurink, Anton J. W.

    2010-01-01

    Epidemiological studies have shown an association between short or disrupted sleep and an increased risk for metabolic disorders. To assess a possible causal relationship, we examined the effects of experimental sleep disturbance on glucose regulation in Wistar rats under controlled laboratory

  5. Hypothalamic vitamin D improves glucose homeostasis and reduces weight

    Science.gov (United States)

    Despite clear associations between vitamin D deficiency and obesity and/or type 2 diabetes, a causal relationship is not established. Vitamin D receptors (VDRs) are found within multiple tissues, including the brain. Given the importance of the brain in controlling both glucose levels and body weigh...

  6. Restraint stress impairs glucose homeostasis through altered insulin ...

    African Journals Online (AJOL)

    The study investigated the potential alteration in the level of insulin and adiponectin, as well as the expression of insulin receptors (INSR) and glucose transporter 4 GLUT-4 in chronic restraint stress rats. Sprague-Dawley rats were randomly divided into two groups: the control group and stress group in which the rats were ...

  7. Deletion of Lkb1 in Pro-Opiomelanocortin Neurons Impairs Peripheral Glucose Homeostasis in Mice

    Science.gov (United States)

    Claret, Marc; Smith, Mark A.; Knauf, Claude; Al-Qassab, Hind; Woods, Angela; Heslegrave, Amanda; Piipari, Kaisa; Emmanuel, Julian J.; Colom, André; Valet, Philippe; Cani, Patrice D.; Begum, Ghazala; White, Anne; Mucket, Phillip; Peters, Marco; Mizuno, Keiko; Batterham, Rachel L.; Giese, K. Peter; Ashworth, Alan; Burcelin, Remy; Ashford, Michael L.; Carling, David; Withers, Dominic J.

    2011-01-01

    OBJECTIVE AMP-activated protein kinase (AMPK) signaling acts as a sensor of nutrients and hormones in the hypothalamus, thereby regulating whole-body energy homeostasis. Deletion of Ampkα2 in pro-opiomelanocortin (POMC) neurons causes obesity and defective neuronal glucose sensing. LKB1, the Peutz-Jeghers syndrome gene product, and Ca2+-calmodulin–dependent protein kinase kinase β (CaMKKβ) are key upstream activators of AMPK. This study aimed to determine their role in POMC neurons upon energy and glucose homeostasis regulation. RESEARCH DESIGN AND METHODS Mice lacking either Camkkβ or Lkb1 in POMC neurons were generated, and physiological, electrophysiological, and molecular biology studies were performed. RESULTS Deletion of Camkkβ in POMC neurons does not alter energy homeostasis or glucose metabolism. In contrast, female mice lacking Lkb1 in POMC neurons (PomcLkb1KO) display glucose intolerance, insulin resistance, impaired suppression of hepatic glucose production, and altered expression of hepatic metabolic genes. The underlying cellular defect in PomcLkb1KO mice involves a reduction in melanocortin tone caused by decreased α-melanocyte–stimulating hormone secretion. However, Lkb1-deficient POMC neurons showed normal glucose sensing, and body weight was unchanged in PomcLkb1KO mice. CONCLUSIONS Our findings demonstrate that LKB1 in hypothalamic POMC neurons plays a key role in the central regulation of peripheral glucose metabolism but not body-weight control. This phenotype contrasts with that seen in mice lacking AMPK in POMC neurons with defects in body-weight regulation but not glucose homeostasis, which suggests that LKB1 plays additional functions distinct from activating AMPK in POMC neurons. PMID:21266325

  8. Deletion of Lkb1 in pro-opiomelanocortin neurons impairs peripheral glucose homeostasis in mice.

    Science.gov (United States)

    Claret, Marc; Smith, Mark A; Knauf, Claude; Al-Qassab, Hind; Woods, Angela; Heslegrave, Amanda; Piipari, Kaisa; Emmanuel, Julian J; Colom, André; Valet, Philippe; Cani, Patrice D; Begum, Ghazala; White, Anne; Mucket, Phillip; Peters, Marco; Mizuno, Keiko; Batterham, Rachel L; Giese, K Peter; Ashworth, Alan; Burcelin, Remy; Ashford, Michael L; Carling, David; Withers, Dominic J

    2011-03-01

    AMP-activated protein kinase (AMPK) signaling acts as a sensor of nutrients and hormones in the hypothalamus, thereby regulating whole-body energy homeostasis. Deletion of Ampkα2 in pro-opiomelanocortin (POMC) neurons causes obesity and defective neuronal glucose sensing. LKB1, the Peutz-Jeghers syndrome gene product, and Ca(2+)-calmodulin-dependent protein kinase kinase β (CaMKKβ) are key upstream activators of AMPK. This study aimed to determine their role in POMC neurons upon energy and glucose homeostasis regulation. Mice lacking either Camkkβ or Lkb1 in POMC neurons were generated, and physiological, electrophysiological, and molecular biology studies were performed. Deletion of Camkkβ in POMC neurons does not alter energy homeostasis or glucose metabolism. In contrast, female mice lacking Lkb1 in POMC neurons (PomcLkb1KO) display glucose intolerance, insulin resistance, impaired suppression of hepatic glucose production, and altered expression of hepatic metabolic genes. The underlying cellular defect in PomcLkb1KO mice involves a reduction in melanocortin tone caused by decreased α-melanocyte-stimulating hormone secretion. However, Lkb1-deficient POMC neurons showed normal glucose sensing, and body weight was unchanged in PomcLkb1KO mice. Our findings demonstrate that LKB1 in hypothalamic POMC neurons plays a key role in the central regulation of peripheral glucose metabolism but not body-weight control. This phenotype contrasts with that seen in mice lacking AMPK in POMC neurons with defects in body-weight regulation but not glucose homeostasis, which suggests that LKB1 plays additional functions distinct from activating AMPK in POMC neurons.

  9. Rictor/mTORC2 facilitates central regulation of energy and glucose homeostasis

    Science.gov (United States)

    Kocalis, Heidi E.; Hagan, Scott L.; George, Leena; Turney, Maxine K.; Siuta, Michael A.; Laryea, Gloria N.; Morris, Lindsey C.; Muglia, Louis J.; Printz, Richard L.; Stanwood, Gregg D.; Niswender, Kevin D.

    2014-01-01

    Insulin signaling in the central nervous system (CNS) regulates energy balance and peripheral glucose homeostasis. Rictor is a key regulatory/structural subunit of the mTORC2 complex and is required for hydrophobic motif site phosphorylation of Akt at serine 473. To examine the contribution of neuronal Rictor/mTORC2 signaling to CNS regulation of energy and glucose homeostasis, we utilized Cre-LoxP technology to generate mice lacking Rictor in all neurons, or in either POMC or AgRP expressing neurons. Rictor deletion in all neurons led to increased fat mass and adiposity, glucose intolerance and behavioral leptin resistance. Disrupting Rictor in POMC neurons also caused obesity and hyperphagia, fasting hyperglycemia and pronounced glucose intolerance. AgRP neuron specific deletion did not impact energy balance but led to mild glucose intolerance. Collectively, we show that Rictor/mTORC2 signaling, especially in POMC-expressing neurons, is important for central regulation of energy and glucose homeostasis. PMID:24944899

  10. Rictor/mTORC2 facilitates central regulation of energy and glucose homeostasis.

    Science.gov (United States)

    Kocalis, Heidi E; Hagan, Scott L; George, Leena; Turney, Maxine K; Siuta, Michael A; Laryea, Gloria N; Morris, Lindsey C; Muglia, Louis J; Printz, Richard L; Stanwood, Gregg D; Niswender, Kevin D

    2014-07-01

    Insulin signaling in the central nervous system (CNS) regulates energy balance and peripheral glucose homeostasis. Rictor is a key regulatory/structural subunit of the mTORC2 complex and is required for hydrophobic motif site phosphorylation of Akt at serine 473. To examine the contribution of neuronal Rictor/mTORC2 signaling to CNS regulation of energy and glucose homeostasis, we utilized Cre-LoxP technology to generate mice lacking Rictor in all neurons, or in either POMC or AgRP expressing neurons. Rictor deletion in all neurons led to increased fat mass and adiposity, glucose intolerance and behavioral leptin resistance. Disrupting Rictor in POMC neurons also caused obesity and hyperphagia, fasting hyperglycemia and pronounced glucose intolerance. AgRP neuron specific deletion did not impact energy balance but led to mild glucose intolerance. Collectively, we show that Rictor/mTORC2 signaling, especially in POMC-expressing neurons, is important for central regulation of energy and glucose homeostasis.

  11. A brain-liver circuit regulates glucose homeostasis.

    Science.gov (United States)

    Pocai, Alessandro; Obici, Silvana; Schwartz, Gary J; Rossetti, Luciano

    2005-01-01

    Increased glucose production (GP) is the major determinant of fasting hyperglycemia in diabetes mellitus. Previous studies suggested that lipid metabolism within specific hypothalamic nuclei is a biochemical sensor for nutrient availability that exerts negative feedback on GP. Here we show that central inhibition of fat oxidation leads to selective activation of brainstem neurons within the nucleus of the solitary tract and the dorsal motor nucleus of the vagus and markedly decreases liver gluconeogenesis, expression of gluconeogenic enzymes, and GP. These effects require central activation of ATP-dependent potassium channels (K(ATP)) and descending fibers within the hepatic branch of the vagus nerve. Thus, hypothalamic lipid sensing potently modulates glucose metabolism via neural circuitry that requires the activation of K(ATP) and selective brainstem neurons and intact vagal input to the liver. This crosstalk between brain and liver couples central nutrient sensing to peripheral nutrient production and its disruption may lead to hyperglycemia.

  12. Glucagon-like peptide-1, glucose homeostasis and diabetes

    DEFF Research Database (Denmark)

    Holst, Jens Juul; Deacon, Carolyn F; Vilsbøll, Tina

    2008-01-01

    Incretins, enhancers of insulin secretion, are essential for glucose tolerance, and a reduction in their function might contribute to poor beta-cell function in patients with type-2 diabetes mellitus. However, at supraphysiological doses, the incretin glucagon-like peptide-1 (GLP-1) protects...... as therapies for type-2 diabetes and have recently reached the market. The pathophysiological basis the clinical use of these therapeutics is reviewed here....

  13. Petalonia improves glucose homeostasis in streptozotocin-induced diabetic mice

    International Nuclear Information System (INIS)

    Kang, Seong-Il; Jin, Young-Jun; Ko, Hee-Chul; Choi, Soo-Youn; Hwang, Joon-Ho; Whang, Ilson; Kim, Moo-Han; Shin, Hye-Sun; Jeong, Hyung-Bok; Kim, Se-Jae

    2008-01-01

    The anti-diabetic potential of Petalonia binghamiae extract (PBE) was evaluated in vivo. Dietary administration of PBE to streptozotocin (STZ)-induced diabetic mice significantly lowered blood glucose levels and improved glucose tolerance. The mode of action by which PBE attenuated diabetes was investigated in vitro using 3T3-L1 cells. PBE treatment stimulated 3T3-L1 adipocyte differentiation as evidenced by increased triglyceride accumulation. At the molecular level, peroxisome proliferator-activated receptor γ (PPARγ) and terminal marker protein aP2, as well as the mRNA of GLUT4 were up-regulated by PBE. In mature adipocytes, PBE significantly stimulated the uptake of glucose and the expression of insulin receptor substrate-1 (IRS-1). Furthermore, PBE increased PPARγ luciferase reporter gene activity in COS-1 cells. Taken together, these results suggest that the in vivo anti-diabetic effect of PBE is mediated by both insulin-like and insulin-sensitizing actions in adipocytes

  14. Differential Role of Insulin/IGF-1 Receptor Signaling in Muscle Growth and Glucose Homeostasis

    Directory of Open Access Journals (Sweden)

    Brian T. O’Neill

    2015-05-01

    Full Text Available Insulin and insulin-like growth factor 1 (IGF-1 are major regulators of muscle protein and glucose homeostasis. To determine how these pathways interact, we generated mice with muscle-specific knockout of IGF-1 receptor (IGF1R and insulin receptor (IR. These MIGIRKO mice showed >60% decrease in muscle mass. Despite a complete lack of insulin/IGF-1 signaling in muscle, MIGIRKO mice displayed normal glucose and insulin tolerance. Indeed, MIGIRKO mice showed fasting hypoglycemia and increased basal glucose uptake. This was secondary to decreased TBC1D1 resulting in increased Glut4 and Glut1 membrane localization. Interestingly, overexpression of a dominant-negative IGF1R in muscle induced glucose intolerance in MIGIRKO animals. Thus, loss of insulin/IGF-1 signaling impairs muscle growth, but not whole-body glucose tolerance due to increased membrane localization of glucose transporters. Nonetheless, presence of a dominant-negative receptor, even in the absence of functional IR/IGF1R, induces glucose intolerance, indicating that interactions between these receptors and other proteins in muscle can impair glucose homeostasis.

  15. Farnesoid X Receptor Deficiency Improves Glucose Homeostasis in Mouse Models of Obesity

    NARCIS (Netherlands)

    Prawitt, Janne; Abdelkarim, Mouaadh; Stroeve, Johanna H. M.; Popescu, Iuliana; Duez, Helene; Velagapudi, Vidya R.; Dumont, Julie; Bouchaert, Emmanuel; van Dijk, Theo H.; Lucas, Anthony; Dorchies, Emilie; Daoudi, Mehdi; Lestavel, Sophie; Gonzalez, Frank J.; Oresic, Matej; Cariou, Bertrand; Kuipers, Folkert; Caron, Sandrine; Staels, Bart

    OBJECTIVE-Bile acids (BA) participate in the maintenance of metabolic homeostasis acting through different signaling pathways. The nuclear BA receptor farnesoid X receptor (FXR) regulates pathways in BA, lipid, glucose, and energy metabolism, which become dysregulated in obesity. However, the role

  16. Pulmonary Ozone Exposure Alters Essential Metabolic Pathways involved in Glucose Homeostasis in the Liver

    Science.gov (United States)

    Pulmonary Ozone Exposure Alters Essential Metabolic Pathways involved in Glucose Homeostasis in the Liver D.B. Johnson, 1 W.O. Ward, 2 V.L. Bass, 2 M.C.J. Schladweiler, 2A.D. Ledbetter, 2 D. Andrews, and U.P. Kodavanti 2 1 Curriculum in Toxicology, UNC School of Medicine, Cha...

  17. Actions of prolonged ghrelin infusion on gastrointestinal transit and glucose homeostasis in humans

    DEFF Research Database (Denmark)

    Falkén, Y; Hellström, P M; Sanger, G J

    2010-01-01

    Ghrelin is produced by enteroendocrine cells in the gastric mucosa and stimulates gastric emptying in healthy volunteers and patients with gastroparesis in short-term studies. The aim of this study was to evaluate effects of intravenous ghrelin on gastrointestinal motility and glucose homeostasis...... during a 6-h infusion in humans....

  18. Lak of influence of glucagon on glucose homeostasis after prolonged exercise in rats

    DEFF Research Database (Denmark)

    Galbo, H; Richter, Erik; Holst, J J

    1977-01-01

    The significance of glucagon for post-exercise glucose homeostasis has been studied in rats fasted overnight. Immediately after exhaustive swimming either rabbit-antiglucagon serum or normal rabbit serum was injected by cardiac puncture. Cardiac blood and samples of liver and muscle tissue were...

  19. Serotonin 2c receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis

    Science.gov (United States)

    Energy and glucose homeostasis are regulated by central serotonin 2C receptors. These receptors are attractive pharmacological targets for the treatment of obesity; however, the identity of the serotonin 2C receptor-expressing neurons that mediate the effects of serotonin and serotonin 2C receptor a...

  20. Acute activation of GLP-1-expressing neurons promotes glucose homeostasis and insulin sensitivity

    Science.gov (United States)

    Glucagon-like peptides are co-released from enteroendocrine L cells in the gut and preproglucagon (PPG) neurons in the Brainstem. PPG-derived GLP-1/2 are probably key neuroendocrine signals for the control of energy balance and glucose Homeostasis. The objective of this study was to determine whethe...

  1. Loss of sugar detection by GLUT2 affects glucose homeostasis in mice.

    Directory of Open Access Journals (Sweden)

    Emilie Stolarczyk

    Full Text Available BACKGROUND: Mammals must sense the amount of sugar available to them and respond appropriately. For many years attention has focused on intracellular glucose sensing derived from glucose metabolism. Here, we studied the detection of extracellular glucose concentrations in vivo by invalidating the transduction pathway downstream from the transporter-detector GLUT2 and measured the physiological impact of this pathway. METHODOLOGY/PRINCIPAL FINDINGS: We produced mice that ubiquitously express the largest cytoplasmic loop of GLUT2, blocking glucose-mediated gene expression in vitro without affecting glucose metabolism. Impairment of GLUT2-mediated sugar detection transiently protected transgenic mice against starvation and streptozotocin-induced diabetes, suggesting that both low- and high-glucose concentrations were not detected. Transgenic mice favored lipid oxidation, and oral glucose was slowly cleared from blood due to low insulin production, despite massive urinary glucose excretion. Kidney adaptation was characterized by a lower rate of glucose reabsorption, whereas pancreatic adaptation was associated with a larger number of small islets. CONCLUSIONS/SIGNIFICANCE: Molecular invalidation of sugar sensing in GLUT2-loop transgenic mice changed multiple aspects of glucose homeostasis, highlighting by a top-down approach, the role of membrane glucose receptors as potential therapeutic targets.

  2. Dietary Fructose and Glucose Differentially Affect Lipid and Glucose Homeostasis1–3

    OpenAIRE

    Schaefer, Ernst J.; Gleason, Joi A.; Dansinger, Michael L.

    2009-01-01

    Absorbed glucose and fructose differ in that glucose largely escapes first-pass removal by the liver, whereas fructose does not, resulting in different metabolic effects of these 2 monosaccharides. In short-term controlled feeding studies, dietary fructose significantly increases postprandial triglyceride (TG) levels and has little effect on serum glucose concentrations, whereas dietary glucose has the opposite effects. When dietary glucose and fructose have been directly compared at ∼20–25% ...

  3. Hormones and the autonomic nervous system are involved in suprachiasmatic nucleus modulation of glucose homeostasis.

    Science.gov (United States)

    Ruiter, Marieke; Buijs, Ruud M; Kalsbeek, Andries

    2006-05-01

    Glucose is one of the most important energy sources for the body in general, and the brain in particular. It is essential for survival to keep glucose levels within strict boundaries. Acute disturbances of glucose homeostasis are rapidly corrected by hormonal and neuronal mechanisms. Furthermore, changes in energy expenditure associated with the light-dark cycle induce variations in the plasma glucose concentration that are more gradual. Organisms take advantage of adapting their internal physiology to the predictable daily changes in energy expenditure, because it enables them to anticipate these changes and to prevent unnecessary disturbance of homeostasis. The hypothalamic biological clock, located in the suprachiasmatic nucleus (SCN), receives light information from the eyes and transmits this information to the rest of the body to synchronize physiology to the environment. Here we review several studies providing evidence for biological clock control of the daily variation in several aspects of glucose metabolism. Although both hormones and the autonomic nervous system can stimulate glucose uptake or production by organs in the periphery, we have shown that the biological clock control of glucose metabolism mostly occurs through the autonomic nervous system. The critical involvement of the biological clock is also indicated by several studies, indicating that disturbance of the biological clock is often associated with metabolic diseases, such as obesity, diabetes mellitus and hypertension.

  4. NPY modulates PYY function in the regulation of energy balance and glucose homeostasis.

    Science.gov (United States)

    Zhang, L; Nguyen, A D; Lee, I-C J; Yulyaningsih, E; Riepler, S J; Stehrer, B; Enriquez, R F; Lin, S; Shi, Y-C; Baldock, P A; Sainsbury, A; Herzog, H

    2012-08-01

    Both the neuronal-derived neuropeptide Y (NPY) and the gut hormone peptide YY (PYY) have been implicated in the regulation of energy balance and glucose homeostasis. However, despite similar affinities for the same Y receptors, the co-ordinated actions of these two peptides in energy and glucose homeostasis remain largely unknown. To investigate the mechanisms and possible interactions between PYY with NPY in the regulation of these processes, we utilized NPY/PYY single and double mutant mouse models and examined parameters of energy balance and glucose homeostasis. PYY(-/-) mice exhibited increased fasting-induced food intake, enhanced fasting and oral glucose-induced serum insulin levels, and an impaired insulin tolerance, - changes not observed in NPY(-/-) mice. Interestingly, whereas PYY deficiency-induced impairment in insulin tolerance remained in NPY(-/-) PYY(-/-) mice, effects of PYY deficiency on fasting-induced food intake and serum insulin concentrations at baseline and after the oral glucose bolus were absent in NPY(-/-) PYY(-/-) mice, suggesting that NPY signalling may be required for PYY's action on insulin secretion and fasting-induced hyperphagia. Moreover, NPY(-/-) PYY(-/-) , but not NPY(-/-) or PYY(-/-) mice had significantly decreased daily food intake, indicating interactive control by NPY and PYY on spontaneous food intake. Furthermore, both NPY(-/-) and PYY(-/-) mice showed significantly reduced respiratory exchange ratio during the light phase, with no additive effects observed in NPY(-/-) PYY(-/-) mice, indicating that NPY and PYY may regulate oxidative fuel selection via partly shared mechanisms. Overall, physical activity and energy expenditure, however, are not significantly altered by NPY and PYY single or double deficiencies. These findings show significant and diverse interactions between NPY and PYY signalling in the regulation of different aspects of energy balance and glucose homeostasis. © 2012 Blackwell Publishing Ltd.

  5. Astrocytes in the nucleus of the solitary tract are activated by low glucose or glucoprivation: evidence for glial involvement in glucose homeostasis.

    Science.gov (United States)

    McDougal, David H; Hermann, Gerlinda E; Rogers, Richard C

    2013-01-01

    Glucose homeostasis is maintained through interplay between central and peripheral control mechanisms which are aimed at storing excess glucose following meals and mobilizing these same stores during periods of fasting. The nucleus of the solitary tract (NST) in the dorsal medulla has long been associated with the central detection of glucose availability and the control of glucose homeostasis. Recent evidence has emerged which supports the involvement of astrocytes in glucose homeostasis. The aim of the present study was to investigate whether NST-astrocytes respond to physiologically relevant decreases in glucose availability, in vitro, as well as to the presence of the glucoprivic compound 2-deoxy-D-Glucose. This report demonstrates that some NST-astrocytes are capable of responding to low glucose or glucoprivation by increasing cytoplasmic calcium; a change that reverses with restoration of normal glucose availability. While some NST-neurons also demonstrate an increase in calcium signaling during low glucose availability, this effect is smaller and somewhat delayed compared to those observed in adjacent astrocytes. TTX did not abolish these hypoglycemia mediated responses of astrocytes, suggesting that NST-astrocytes may be directly sensing low glucose levels as opposed to responding to neuronal detection of hypoglycemia. Thus, chemodetection of low glucose by NST-astrocytes may play an important role in the autonomic regulation of glucose homeostasis.

  6. Astrocytes in the nucleus of the solitary tract are activated by low glucose or glucoprivation: evidence for glial involvement in glucose homeostasis.

    Directory of Open Access Journals (Sweden)

    David Harry McDougal

    2013-12-01

    Full Text Available Glucose homeostasis is maintained through interplay between central and peripheral control mechanisms which are aimed at storing excess glucose following meals and mobilizing these same stores during periods of fasting. The nucleus of the solitary tract (NST in the dorsal medulla has long been associated with the central detection of glucose availability and the control of glucose homeostasis. Recent evidence has emerged which supports the involvement of astrocytes in glucose homeostasis. The aim of the present study was to investigate whether NST-astrocytes respond to physiologically relevant decreases in glucose availability, in vitro, as well as to the presence of the glucoprivic compound 2-deoxy-D-Glucose. This report demonstrates that some NST-astrocytes are capable of responding to low glucose or glucoprivation by increasing cytoplasmic calcium; a change that reverses with restoration of normal glucose availability. While some NST-neurons also demonstrate an increase in calcium signaling during low glucose availability, this effect is smaller and somewhat delayed compared to those observed in adjacent astrocytes. TTX did not abolish these hypoglycemia mediated responses of astrocytes, suggesting that NST-astrocytes may be directly sensing low glucose levels as opposed to responding to neuronal detection of hypoglycemia. Thus, chemodetection of low glucose by NST-astrocytes may play an important role in the autonomic regulation of glucose homeostasis.

  7. Serine racemase is expressed in islets and contributes to the regulation of glucose homeostasis.

    Science.gov (United States)

    Lockridge, Amber D; Baumann, Daniel C; Akhaphong, Brian; Abrenica, Alleah; Miller, Robert F; Alejandro, Emilyn U

    2016-11-01

    NMDA receptors (NMDARs) have recently been discovered as functional regulators of pancreatic β-cell insulin secretion. While these excitatory receptor channels have been extensively studied in the brain for their role in synaptic plasticity and development, little is known about how they work in β-cells. In neuronal cells, NMDAR activation requires the simultaneous binding of glutamate and a rate-limiting co-agonist, such as D-serine. D-serine levels and availability in most of the brain rely on endogenous synthesis by the enzyme serine racemase (Srr). Srr transcripts have been reported in human and mouse islets but it is not clear whether Srr is functionally expressed in β-cells or what its role in the pancreas might be. In this investigation, we reveal that Srr protein is highly expressed in primary human and mouse β-cells. Mice with whole body deletion of Srr (Srr KO) show improved glucose tolerance through enhanced insulin secretory capacity, possibly through Srr-mediated alterations in islet NMDAR expression and function. We observed elevated insulin sensitivity in some animals, suggesting Srr metabolic regulation in other peripheral organs as well. Srr expression in neonatal and embryonic islets, and adult deficits in Srr KO pancreas weight and islet insulin content, point toward a potential role for Srr in pancreatic development. These data reveal the first evidence that Srr may regulate glucose homeostasis in peripheral tissues and provide circumstantial evidence that D-serine may be an endogenous islet NMDAR co-agonist in β-cells.

  8. A potential role for muscle in glucose homeostasis: in vivo kinetic studies in glycogen storage disease type 1a and fructose-1,6-bisphosphatase deficiency

    NARCIS (Netherlands)

    Huidekoper, Hidde H.; Visser, Gepke; Ackermans, Mariëtte T.; Sauerwein, Hans P.; Wijburg, Frits A.

    2010-01-01

    A potential role for muscle in glucose homeostasis was recently suggested based on characterization of extrahepatic and extrarenal glucose-6-phosphatase (glucose-6-phosphatase-beta). To study the role of extrahepatic tissue in glucose homeostasis during fasting glucose kinetics were studied in two

  9. Neonatal hypothyroidism affects testicular glucose homeostasis through increased oxidative stress in prepubertal mice: effects on GLUT3, GLUT8 and Cx43.

    Science.gov (United States)

    Sarkar, D; Singh, S K

    2017-07-01

    Thyroid hormones (THs) play an important role in maintaining the link between metabolism and reproduction and the altered THs status is associated with induction of oxidative stress in various organs like brain, heart, liver and testis. Further, reactive oxygen species play a pivotal role in regulation of glucose homeostasis in several organs, and glucose utilization by Leydig cells is essential for testosterone biosynthesis and thus is largely dependent on glucose transporter 8 (GLUT8). Glucose uptake by Sertoli cells is mediated through glucose transporter 3 (GLUT3) under the influence of THs to meet energy requirement of developing germ cells. THs also modulate level of gap junctional protein such as connexin 43 (Cx43), a potential regulator of cell proliferation and apoptosis in the seminiferous epithelium. Although the role of transient neonatal hypothyroidism in adult testis in terms of testosterone production is well documented, the effect of THs deficiency in early developmental period and its role in testicular glucose homeostasis and oxidative stress with reference to Cx43 in immature mice remain unknown. Therefore, the present study was conducted to evaluate the effect of neonatal hypothyroidism on testicular glucose homeostasis and oxidative stress at postnatal days (PND) 21 and 28 in relation to GLUT3, GLUT8 and Cx43. Hypothyroidism induced by 6-propyl-2-thiouracil (PTU) markedly decreased testicular glucose level with considerable reduction in expression level of GLUT3 and GLUT8. Likewise, lactate dehydrogenase (LDH) activity and intratesticular concentration of lactate were also decreased in hypothyroid mice. There was also a rise in germ cell apoptosis with increased expression of caspase-3 in PTU-treated mice. Further, neonatal hypothyroidism affected germ cell proliferation with decreased expression of proliferating cell nuclear antigen (PCNA) and Cx43. In conclusion, our results suggest that neonatal hypothyroidism alters testicular glucose

  10. Central effects of beta-endorphins on glucose homeostasis in the conscious dog

    International Nuclear Information System (INIS)

    Radosevich, P.M.; Lacy, D.B.; Brown, L.L.; Williams, P.E.; Abumrad, N.N.

    1989-01-01

    The effects of centrally administered beta-endorphins on glucose homeostasis in the conscious dog were studied. Intracerebroventricular administration of beta-endorphin (0.2 mg/h) caused a 70% increase in plasma glucose. The mechanism of the hyperglycemia was twofold: there was an early increase in glucose production and a late inhibition of glucose clearance. These changes are explained by marked increases in plasma epinephrine (30-fold) and norepinephrine (6-fold) that occurred during infusion of beta-endorphin. Central administration of beta-endorphin also resulted in increased levels of adrenocorticotropic hormone and cortisol. In addition there was an increase in plasma insulin but no increase in plasma glucagon. Intravenous administration of beta-endorphin did not alter glucose homeostasis. Intracerebroventricular administration of acetylated beta-endorphin did not perturb glucose kinetics or any of the hormones that changed during infusion of the unacetylated peptide. We conclude that beta-endorphin acts centrally to cause hyperglycemia by stimulating sympathetic outflow and the pituitary-adrenal axis. Acetylation of beta-endorphin abolishes the in vivo activity of the peptide

  11. Intra-islet glucagon secretion and action in the regulation of glucose homeostasis.

    Directory of Open Access Journals (Sweden)

    Qinghua eWang

    2013-01-01

    Full Text Available Glucagon, a key hormone in the regulation of glucose homeostasis, acts as a counter-regulatory hormone to insulin by promoting hepatic glucose output. Under normal conditions, insulin and glucagon operate in concert to maintain the glucose level within a narrow physiological range. In diabetes, however, while insulin secretion or action is insufficient, the production and secretion of glucagon are excessive, contributing to the development of diabetic hyperglycemia. Within an islet, intra-islet insulin, in cooperation with intra-islet GABA, suppresses glucagon secretion via direct modulation of -cell intracellular signaling pathways involving Akt activation, GABA receptor phosphorylation and the receptor plasma membrane translocation, while intra-islet glucagon plays an important role in modulating β-cell function and insulin secretion. Defects in the insulin-glucagon fine-tuning machinery may result in β-cell glucose incompetence, leading to unsuppressed glucagon secretion and subsequent hyperglycemia, which often occur under extreme conditions of glucose influx or efflux. Therefore, deciphering the precise molecular mechanisms underlying glucagon secretion and action will facilitate our understanding of glucagon physiology, in particular, its role in regulating islet β-cell function, and hence the mechanisms behind body glucose homeostasis.

  12. Central effects of beta-endorphins on glucose homeostasis in the conscious dog

    Energy Technology Data Exchange (ETDEWEB)

    Radosevich, P.M.; Lacy, D.B.; Brown, L.L.; Williams, P.E.; Abumrad, N.N.

    1989-02-01

    The effects of centrally administered beta-endorphins on glucose homeostasis in the conscious dog were studied. Intracerebroventricular administration of beta-endorphin (0.2 mg/h) caused a 70% increase in plasma glucose. The mechanism of the hyperglycemia was twofold: there was an early increase in glucose production and a late inhibition of glucose clearance. These changes are explained by marked increases in plasma epinephrine (30-fold) and norepinephrine (6-fold) that occurred during infusion of beta-endorphin. Central administration of beta-endorphin also resulted in increased levels of adrenocorticotropic hormone and cortisol. In addition there was an increase in plasma insulin but no increase in plasma glucagon. Intravenous administration of beta-endorphin did not alter glucose homeostasis. Intracerebroventricular administration of acetylated beta-endorphin did not perturb glucose kinetics or any of the hormones that changed during infusion of the unacetylated peptide. We conclude that beta-endorphin acts centrally to cause hyperglycemia by stimulating sympathetic outflow and the pituitary-adrenal axis. Acetylation of beta-endorphin abolishes the in vivo activity of the peptide.

  13. Maintenance of Gastrointestinal Glucose Homeostasis by the Gut-Brain Axis.

    Science.gov (United States)

    Chen, Xiyue; Eslamfam, Shabnam; Fang, Luoyun; Qiao, Shiyan; Ma, Xi

    2017-01-01

    Gastrointestinal homeostasis is a dynamic balance under the interaction between the host, GI tract, nutrition and energy metabolism. Glucose is the main energy source in living cells. Thus, glucose metabolic disorders can impair normal cellular function and endanger organisms' health. Diseases that are associated with glucose metabolic disorders such as obesity, diabetes, hypertension, and other metabolic syndromes are in fact life threatening. Digestive system is responsible for food digestion and nutrient absorption. It is also involved in neuronal, immune, and endocrine pathways. In addition, the gut microbiota plays an essential role in initiating signal transduction, and communication between the enteric and central nervous system. Gut-brain axis is composed of enteric neural system, central neural system, and all the efferent and afferent neurons that are involved in signal transduction between the brain and gut-brain. Gut-brain axis is influenced by the gut-microbiota as well as numerous neurotransmitters. Properly regulated gut-brain axis ensures normal digestion, absorption, energy production, and subsequently maintenance of glucose homeostasis. Understanding the underlying regulatory mechanisms of gut-brain axis involved in gluose homeostasis would enable us develop more efficient means of prevention and management of metabolic disease such as diabetic, obesity, and hypertension. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Leptin rapidly improves glucose homeostasis in obese mice by increasing hypothalamic insulin sensitivity.

    Science.gov (United States)

    Koch, Christiane; Augustine, Rachael A; Steger, Juliane; Ganjam, Goutham K; Benzler, Jonas; Pracht, Corinna; Lowe, Chrishanthi; Schwartz, Michael W; Shepherd, Peter R; Anderson, Greg M; Grattan, David R; Tups, Alexander

    2010-12-01

    Obesity is associated with resistance to the actions of both leptin and insulin via mechanisms that remain incompletely understood. To investigate whether leptin resistance per se contributes to insulin resistance and impaired glucose homeostasis, we investigated the effect of acute leptin administration on glucose homeostasis in normal as well as leptin- or leptin receptor-deficient mice. In hyperglycemic, leptin-deficient Lep(ob/ob) mice, leptin acutely and potently improved glucose metabolism, before any change of body fat mass, via a mechanism involving the p110α and β isoforms of phosphatidylinositol-3-kinase (PI3K). Unlike insulin, however, the anti-diabetic effect of leptin occurred independently of phospho-AKT, a major downstream target of PI3K, and instead involved enhanced sensitivity of the hypothalamus to insulin action upstream of PI3K, through modulation of IRS1 (insulin receptor substrate 1) phosphorylation. These data suggest that leptin resistance, as occurs in obesity, reduces the hypothalamic response to insulin and thereby impairs peripheral glucose homeostasis, contributing to the development of type 2 diabetes.

  15. Phosphatidyl inositol 3-kinase signaling in hypothalamic proopiomelanocortin neurons contributes to the regulation of glucose homeostasis.

    Science.gov (United States)

    Hill, Jennifer W; Xu, Yong; Preitner, Frederic; Fukuda, Makota; Cho, You-Ree; Luo, Ji; Balthasar, Nina; Coppari, Roberto; Cantley, Lewis C; Kahn, Barbara B; Zhao, Jean J; Elmquist, Joel K

    2009-11-01

    Recent studies demonstrated a role for hypothalamic insulin and leptin action in the regulation of glucose homeostasis. This regulation involves proopiomelanocortin (POMC) neurons because suppression of phosphatidyl inositol 3-kinase (PI3K) signaling in these neurons blunts the acute effects of insulin and leptin on POMC neuronal activity. In the current study, we investigated whether disruption of PI3K signaling in POMC neurons alters normal glucose homeostasis using mouse models designed to both increase and decrease PI3K-mediated signaling in these neurons. We found that deleting p85alpha alone induced resistance to diet-induced obesity. In contrast, deletion of the p110alpha catalytic subunit of PI3K led to increased weight gain and adipose tissue along with reduced energy expenditure. Independent of these effects, increased PI3K activity in POMC neurons improved insulin sensitivity, whereas decreased PI3K signaling resulted in impaired glucose regulation. These studies show that activity of the PI3K pathway in POMC neurons is involved in not only normal energy regulation but also glucose homeostasis.

  16. Molecular aspects of glucose homeostasis in skeletal muscle--A focus on the molecular mechanisms of insulin resistance.

    Science.gov (United States)

    Carnagarin, Revathy; Dharmarajan, Arun M; Dass, Crispin R

    2015-12-05

    Among all the varied actions of insulin, regulation of glucose homeostasis is the most critical and intensively studied. With the availability of glucose from nutrient metabolism, insulin action in muscle results in increased glucose disposal via uptake from the circulation and storage of excess, thereby maintaining euglycemia. This major action of insulin is executed by redistribution of the glucose transporter protein, GLUT4 from intracellular storage sites to the plasma membrane and storage of glucose in the form of glycogen which also involves modulation of actin dynamics that govern trafficking of all the signal proteins of insulin signal transduction. The cellular mechanisms responsible for these trafficking events and the defects associated with insulin resistance are largely enigmatic, and this review provides a consolidated overview of the various molecular mechanisms involved in insulin-dependent glucose homeostasis in skeletal muscle, as insulin resistance at this major peripheral site impacts whole body glucose homeostasis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. PCAF Improves Glucose Homeostasis by Suppressing the Gluconeogenic Activity of PGC-1α

    Directory of Open Access Journals (Sweden)

    Cheng Sun

    2014-12-01

    Full Text Available PGC-1α plays a central role in hepatic gluconeogenesis and has been implicated in the onset of type 2 diabetes. Acetylation is an important posttranslational modification for regulating the transcriptional activity of PGC-1α. Here, we show that PCAF is a pivotal acetyltransferase for acetylating PGC-1α in both fasted and diabetic states. PCAF acetylates two lysine residues K328 and K450 in PGC-1α, which subsequently triggers its proteasomal degradation and suppresses its transcriptional activity. Adenoviral-mediated expression of PCAF in the obese mouse liver greatly represses gluconeogenic enzyme activation and glucose production and improves glucose homeostasis and insulin sensitivity. Moreover, liver-specific knockdown of PCAF stimulates PGC-1α activity, resulting in an increase in blood glucose and hepatic glucose output. Our results suggest that PCAF might be a potential pharmacological target for developing agents against metabolic disorders associated with hyperglycemia, such as obesity and diabetes.

  18. The effect of different levels of dietary restriction on glucose homeostasis and metabolic memory.

    Science.gov (United States)

    Matyi, Stephanie; Jackson, Jordan; Garrett, Karla; Deepa, Sathyaseelan S; Unnikrishnan, Archana

    2018-02-17

    Over the past 50 years, dietary restriction (DR) has been shown to extend the life span of a wide variety of organisms. A hallmark feature of DR is improved glucose homeostasis resulting in increased glucose tolerance and insulin sensitivity of animals ranging from rodents to humans. In this study, we demonstrate the early effects of varying levels of DR on glucose tolerance. Within 10 days of 40% DR, glucose tolerance was significantly improved and by 120 days; 10 and 20% DR also showed enhanced glucose tolerance. All three levels of DR showed reduced adiposity, increased expression of genes involved in fat turnover, and a reduction in the expression for markers of inflammation. Studies have shown that mice fed a DR diet retained metabolic memory in terms of improved glucose tolerance even after DR is discontinued. We show that 40% DR not only has an early effect on glucose tolerance but also maintained it after DR was discontinued for 2 months. Therefore, improvement in glucose tolerance is brought about by all three levels of DR but the metabolic memory is not dose responsive.

  19. Ion channels in the central regulation of energy and glucose homeostasis

    Directory of Open Access Journals (Sweden)

    Jong-Woo eSohn

    2013-05-01

    Full Text Available Ion channels are critical regulators of neuronal excitability and synaptic function in the brain. Recent evidence suggests that ion channels expressed by neurons within the brain are responsible for regulating energy and glucose homeostasis. In addition, the central effects of neurotransmitters and hormones are at least in part achieved by modifications of ion channel activity. This review focuses on ion channels and their neuronal functions followed by a discussion of the identified roles for specific ion channels in the central pathways regulating food intake, energy expenditure, and glucose balance.

  20. Mice lacking ANGPTL8 (Betatrophin) manifest disrupted triglyceride metabolism without impaired glucose homeostasis.

    Science.gov (United States)

    Wang, Yan; Quagliarini, Fabiana; Gusarova, Viktoria; Gromada, Jesper; Valenzuela, David M; Cohen, Jonathan C; Hobbs, Helen H

    2013-10-01

    Angiopoietin-like protein (ANGPTL)8 (alternatively called TD26, RIFL, Lipasin, and Betatrophin) is a newly recognized ANGPTL family member that has been implicated in both triglyceride (TG) and glucose metabolism. Hepatic overexpression of ANGPTL8 causes hypertriglyceridemia and increased insulin secretion. Here we examined the effects of inactivating Angptl8 on TG and glucose metabolism in mice. Angptl8 knockout (Angptl8(-/-)) mice gained weight more slowly than wild-type littermates due to a selective reduction in adipose tissue accretion. Plasma levels of TGs of the Angptl8(-/-) mice were similar to wild-type animals in the fasted state but paradoxically decreased after refeeding. The lower TG levels were associated with both a reduction in very low density lipoprotein secretion and an increase in lipoprotein lipase (LPL) activity. Despite the increase in LPL activity, the uptake of very low density lipoprotein-TG is markedly reduced in adipose tissue but preserved in hearts of fed Angptl8(-/-) mice. Taken together, these data indicate that ANGPTL8 plays a key role in the metabolic transition between fasting and refeeding; it is required to direct fatty acids to adipose tissue for storage in the fed state. Finally, glucose and insulin tolerance testing revealed no alterations in glucose homeostasis in mice fed either a chow or high fat diet. Thus, although absence of ANGPTL8 profoundly disrupts TG metabolism, we found no evidence that it is required for maintenance of glucose homeostasis.

  1. Ion channels in the central regulation of energy and glucose homeostasis

    OpenAIRE

    Sohn, Jong-Woo

    2013-01-01

    Ion channels are critical regulators of neuronal excitability and synaptic function in the brain. Recent evidence suggests that ion channels expressed by neurons within the brain are responsible for regulating energy and glucose homeostasis. In addition, the central effects of neurotransmitters and hormones are at least in part achieved by modifications of ion channel activity. This review focuses on ion channels and their neuronal functions followed by a discussion of the identified roles fo...

  2. Glucose homeostasis in children with falciparum malaria: precursor supply limits gluconeogenesis and glucose production

    NARCIS (Netherlands)

    Dekker, E.; Hellerstein, M. K.; Romijn, J. A.; Neese, R. A.; Peshu, N.; Endert, E.; Marsh, K.; Sauerwein, H. P.

    1997-01-01

    To evaluate glucose kinetics in children with falciparum malaria, basal glucose production and gluconeogenesis and an estimate of the flux of the gluconeogenic precursors were measured in Kenyan children with uncomplicated falciparum malaria before (n = 11) and during infusion of alanine (1.5

  3. Role of orexins in the central and peripheral regulation of glucose homeostasis: Evidences & mechanisms.

    Science.gov (United States)

    Rani, Monika; Kumar, Raghuvansh; Krishan, Pawan

    2018-04-01

    Orexins (A & B), neuropeptides of hypothalamic origin, act through G-protein coupled receptors, orexin 1 receptor (OX 1 R) and orexin 2 receptor (OX 2 R). The wide projection of orexin neurons in the hypothalamic region allows them to interact with the other neurons and regulate food intake, emotional status, sleep wake cycle and energy metabolism. The autonomic nervous system plays an important regulatory role in the energy metabolism as well as glucose homeostasis. Orexin neurons are also under the control of GABAergic neurons. Emerging preclinical as well as clinical research has reported the role of orexins in the glucose homeostasis since orexins are involved in hypothalamic metabolism circuitry and also rely on sensing peripheral metabolic signals such as gut, adipose derived and pancreatic peptides. Apart from the hypothalamic origin, integration and control in various physiological functions, peripheral origin in wide organs, raises the possibility of use of orexins as a therapeutic biomarker in the management of metabolic disorders. The present review focuses the central as well as peripheral roles of orexins in the glucose homeostasis. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Leptin Is Required for Glucose Homeostasis after Roux-en-Y Gastric Bypass in Mice.

    Directory of Open Access Journals (Sweden)

    Mohamad Mokadem

    Full Text Available Leptin, the protein product of the ob gene, increases energy expenditure and reduces food intake, thereby promoting weight reduction. Leptin also regulates glucose homeostasis and hepatic insulin sensitivity via hypothalamic proopiomelanocortin neurons in mice. Roux-en-Y gastric bypass (RYGB induces weight loss that is substantial and sustained despite reducing plasma leptin levels. In addition, patients who fail to undergo diabetes remission after RYGB are hypoletinemic compared to those who do and to lean controls. We have previously demonstrated that the beneficial effects of RYGB in mice require the melanocortin-4 receptor, a downstream effector of leptin action. Based on these observations, we hypothesized that leptin is required for sustained weight reduction and improved glucose homeostasis observed after RYGB.To investigate this hypothesis, we performed RYGB or sham operations on leptin-deficient ob/ob mice maintained on regular chow. To investigate whether leptin is involved in post-RYGB weight maintenance, we challenged post-surgical mice with high fat diet.RYGB reduced total body weight, fat and lean mass and caused reduction in calorie intake in ob/ob mice. However, it failed to improve glucose tolerance, glucose-stimulated plasma insulin, insulin tolerance, and fasting plasma insulin. High fat diet eliminated the reduction in calorie intake observed after RYGB in ob/ob mice and promoted weight regain, although not to the same extent as in sham-operated mice. We conclude that leptin is required for the effects of RYGB on glucose homeostasis but not body weight or composition in mice. Our data also suggest that leptin may play a role in post-RYGB weight maintenance.

  5. Insulin Sensitivity and Glucose Homeostasis Can Be Influenced by Metabolic Acid Load

    Directory of Open Access Journals (Sweden)

    Lucio Della Guardia

    2018-05-01

    Full Text Available Recent epidemiological findings suggest that high levels of dietary acid load can affect insulin sensitivity and glucose metabolism. Consumption of high protein diets results in the over-production of metabolic acids which has been associated with the development of chronic metabolic disturbances. Mild metabolic acidosis has been shown to impair peripheral insulin action and several epidemiological findings suggest that metabolic acid load markers are associated with insulin resistance and impaired glycemic control through an interference intracellular insulin signaling pathways and translocation. In addition, higher incidence of diabetes, insulin resistance, or impaired glucose control have been found in subjects with elevated metabolic acid load markers. Hence, lowering dietary acid load may be relevant for improving glucose homeostasis and prevention of type 2 diabetes development on a long-term basis. However, limitations related to patient acid load estimation, nutritional determinants, and metabolic status considerably flaws available findings, and the lack of solid data on the background physiopathology contributes to the questionability of results. Furthermore, evidence from interventional studies is very limited and the trials carried out report no beneficial results following alkali supplementation. Available literature suggests that poor acid load control may contribute to impaired insulin sensitivity and glucose homeostasis, but it is not sufficiently supportive to fully elucidate the issue and additional well-designed studies are clearly needed.

  6. CD14 deficiency impacts glucose homeostasis in mice through altered adrenal tone.

    Directory of Open Access Journals (Sweden)

    James L Young

    Full Text Available The toll-like receptors comprise one of the most conserved components of the innate immune system, signaling the presence of molecules of microbial origin. It has been proposed that signaling through TLR4, which requires CD14 to recognize bacterial lipopolysaccharide (LPS, may generate low-grade inflammation and thereby affect insulin sensitivity and glucose metabolism. To examine the long-term influence of partial innate immune signaling disruption on glucose homeostasis, we analyzed knockout mice deficient in CD14 backcrossed into the diabetes-prone C57BL6 background at 6 or 12 months of age. CD14-ko mice, fed either normal or high-fat diets, displayed significant glucose intolerance compared to wild type controls. They also displayed elevated norepinephrine urinary excretion and increased adrenal medullary volume, as well as an enhanced norepinephrine secretory response to insulin-induced hypoglycemia. These results point out a previously unappreciated crosstalk between innate immune- and sympathoadrenal- systems, which exerts a major long-term effect on glucose homeostasis.

  7. Glucose Homeostasis During Short-term and Prolonged Exposure to High Altitudes

    Science.gov (United States)

    Ader, Marilyn; Bergman, Richard N.

    2015-01-01

    Most of the literature related to high altitude medicine is devoted to the short-term effects of high-altitude exposure on human physiology. However, long-term effects of living at high altitudes may be more important in relation to human disease because more than 400 million people worldwide reside above 1500 m. Interestingly, individuals living at higher altitudes have a lower fasting glycemia and better glucose tolerance compared with those who live near sea level. There is also emerging evidence of the lower prevalence of both obesity and diabetes at higher altitudes. The mechanisms underlying improved glucose control at higher altitudes remain unclear. In this review, we present the most current evidence about glucose homeostasis in residents living above 1500 m and discuss possible mechanisms that could explain the lower fasting glycemia and lower prevalence of obesity and diabetes in this population. Understanding the mechanisms that regulate and maintain the lower fasting glycemia in individuals who live at higher altitudes could lead to new therapeutics for impaired glucose homeostasis. PMID:25675133

  8. CD14 Deficiency Impacts Glucose Homeostasis in Mice through Altered Adrenal Tone

    Science.gov (United States)

    Young, James L.; Mora, Alfonso; Cerny, Anna; Czech, Michael P.; Woda, Bruce; Kurt-Jones, Evelyn A.; Finberg, Robert W.; Corvera, Silvia

    2012-01-01

    The toll-like receptors comprise one of the most conserved components of the innate immune system, signaling the presence of molecules of microbial origin. It has been proposed that signaling through TLR4, which requires CD14 to recognize bacterial lipopolysaccharide (LPS), may generate low-grade inflammation and thereby affect insulin sensitivity and glucose metabolism. To examine the long-term influence of partial innate immune signaling disruption on glucose homeostasis, we analyzed knockout mice deficient in CD14 backcrossed into the diabetes-prone C57BL6 background at 6 or 12 months of age. CD14-ko mice, fed either normal or high-fat diets, displayed significant glucose intolerance compared to wild type controls. They also displayed elevated norepinephrine urinary excretion and increased adrenal medullary volume, as well as an enhanced norepinephrine secretory response to insulin-induced hypoglycemia. These results point out a previously unappreciated crosstalk between innate immune- and sympathoadrenal- systems, which exerts a major long-term effect on glucose homeostasis. PMID:22253759

  9. Requirement of the ATM/p53 tumor suppressor pathway for glucose homeostasis.

    Science.gov (United States)

    Armata, Heather L; Golebiowski, Diane; Jung, Dae Young; Ko, Hwi Jin; Kim, Jason K; Sluss, Hayla K

    2010-12-01

    Ataxia telangiectasia (A-T) patients can develop multiple clinical pathologies, including neuronal degeneration, an elevated risk of cancer, telangiectasias, and growth retardation. Patients with A-T can also exhibit an increased risk of insulin resistance and type 2 diabetes. The ATM protein kinase, the product of the gene mutated in A-T patients (Atm), has been implicated in metabolic disease, which is characterized by insulin resistance and increased cholesterol and lipid levels, blood pressure, and atherosclerosis. ATM phosphorylates the p53 tumor suppressor on a site (Ser15) that regulates transcription activity. To test whether the ATM pathway that regulates insulin resistance is mediated by p53 phosphorylation, we examined insulin sensitivity in mice with a germ line mutation that replaces the p53 phosphorylation site with alanine. The loss of p53 Ser18 (murine Ser15) led to increased metabolic stress, including severe defects in glucose homeostasis. The mice developed glucose intolerance and insulin resistance. The insulin resistance correlated with the loss of antioxidant gene expression and decreased insulin signaling. N-Acetyl cysteine (NAC) treatment restored insulin signaling in late-passage primary fibroblasts. The addition of an antioxidant in the diet rendered the p53 Ser18-deficient mice glucose tolerant. This analysis demonstrates that p53 phosphorylation on an ATM site is an important mechanism in the physiological regulation of glucose homeostasis.

  10. Intermittent hypoxia training in prediabetes patients: Beneficial effects on glucose homeostasis, hypoxia tolerance and gene expression.

    Science.gov (United States)

    Serebrovska, Tetiana V; Portnychenko, Alla G; Drevytska, Tetiana I; Portnichenko, Vladimir I; Xi, Lei; Egorov, Egor; Gavalko, Anna V; Naskalova, Svitlana; Chizhova, Valentina; Shatylo, Valeriy B

    2017-09-01

    The present study aimed at examining beneficial effects of intermittent hypoxia training (IHT) under prediabetic conditions. We investigate the effects of three-week IHT on blood glucose level, tolerance to acute hypoxia, and leukocyte mRNA expression of hypoxia inducible factor 1α (HIF-1α) and its target genes, i.e. insulin receptor, facilitated glucose transporter-solute carrier family-2, and potassium voltage-gated channel subfamily J. Seven healthy and 11 prediabetic men and women (44-70 years of age) were examined before, next day and one month after three-week IHT (3 sessions per week, each session consisting 4 cycles of 5-min 12% O 2 and 5-min room air breathing). We found that IHT afforded beneficial effects on glucose homeostasis in patients with prediabetes reducing fasting glucose and during standard oral glucose tolerance test. The most pronounced positive effects were observed at one month after IHT termination. IHT also significantly increased the tolerance to acute hypoxia (i.e. SaO 2 level at 20th min of breathing with 12% O 2 ) and improved functional parameters of respiratory and cardiovascular systems. IHT stimulated HIF-1α mRNA expression in blood leukocytes in healthy and prediabetic subjects, but in prediabetes patients the maximum increase was lagged. The greatest changes in mRNA expression of HIF-1α target genes occurred a month after IHT and coincided with the largest decrease in blood glucose levels. The higher expression of HIF-1α was positively associated with higher tolerance to hypoxia and better glucose homeostasis. In conclusion, our results suggest that IHT may be useful for preventing the development of type 2 diabetes. Impact statement The present study investigated the beneficial effects of intermittent hypoxia training (IHT) in humans under prediabetic conditions. We found that three-week moderate IHT induced higher HIF-1α mRNA expressions as well as its target genes, which were positively correlated with higher tolerance

  11. The impact of transsphenoidal surgery on glucose homeostasis and insulin resistance in acromegaly.

    Science.gov (United States)

    Stelmachowska-Banaś, Maria; Zieliński, Grzegorz; Zdunowski, Piotr; Podgórski, Jan; Zgliczyński, Wocjiech

    2011-01-01

    Impaired glucose tolerance and overt diabetes mellitus are frequently associated with acro-megaly. The aim of this study was to find out whether these alterations could be reversed after transsphenoidal surgery. Two hundred and thirty-nine acromegalic patients were studied before and 6-12 months after transsphenoidal surgery. Diagnosis of active acromegaly was established on the basis of widely recognized criteria. In each patient, glucose and insulin concentrations were assessed during the 75 γ oral glucose tolerance test (OGTT). To estimate insulin resistance, we used homeostasis model assessment (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI). At the moment of diagnosis, diabetes mellitus was present in 25% of the acromegalic patients. After surgery, the pre-valence of diabetes mellitus normalized to the level present in the general Polish population. We found a statistically significant reduction after surgery in plasma glucose levels both fasting (89.45 ± 13.92 mg/dL vs. 99.12 ± 17.33 mg/dL, p surgery compared to the moment of diagnosis (15.44 ± 8.80 mIU/mL vs. 23.40 ± 10.24 mIU/mL, p transsphenoidal surgery, there was a significant reduction in HOMA-IR (3.08 vs. 6.76, p surgery in fasting glucose and insulin levels between patients with controlled and in-adequately controlled disease. We conclude that in acromegalic patients glucose homeostasis alterations and insulin sensitivity can be normalized after transsphenoidal surgery, even if strict biochemical cure criteria are not fulfilled.

  12. Interactive effects of neonatal exposure to monosodium glutamate and aspartame on glucose homeostasis

    Directory of Open Access Journals (Sweden)

    Collison Kate S

    2012-06-01

    Full Text Available Abstract Background Recent evidence suggests that the effects of certain food additives may be synergistic or additive. Aspartame (ASP and Monosodium Glutamate (MSG are ubiquitous food additives with a common moiety: both contain acidic amino acids which can act as neurotransmitters, interacting with NMDA receptors concentrated in areas of the Central Nervous System regulating energy expenditure and conservation. MSG has been shown to promote a neuroendocrine dysfunction when large quantities are administered to mammals during the neonatal period. ASP is a low-calorie dipeptide sweetener found in a wide variety of diet beverages and foods. However, recent reports suggest that ASP may promote weight gain and hyperglycemia in a zebrafish nutritional model. Methods We investigated the effects of ASP, MSG or a combination of both on glucose and insulin homeostasis, weight change and adiposity, in C57BL/6 J mice chronically exposed to these food additives commencing in-utero, compared to an additive-free diet. Pearson correlation analysis was used to investigate the associations between body characteristics and variables in glucose and insulin homeostasis. Results ASP alone (50 mg/Kgbw/day caused an increase in fasting blood glucose of 1.6-fold, together with reduced insulin sensitivity during an Insulin Tolerance Test (ITT P  Conclusions Aspartame exposure may promote hyperglycemia and insulin intolerance. MSG may interact with aspartame to further impair glucose homeostasis. This is the first study to ascertain the hyperglycemic effects of chronic exposure to a combination of these commonly consumed food additives; however these observations are limited to a C57BL/6 J mouse model. Caution should be applied in extrapolating these findings to other species.

  13. Helicobacter pylori colonization ameliorates glucose homeostasis in mice through a PPAR γ-dependent mechanism.

    Science.gov (United States)

    Bassaganya-Riera, Josep; Dominguez-Bello, Maria Gloria; Kronsteiner, Barbara; Carbo, Adria; Lu, Pinyi; Viladomiu, Monica; Pedragosa, Mireia; Zhang, Xiaoying; Sobral, Bruno W; Mane, Shrinivasrao P; Mohapatra, Saroj K; Horne, William T; Guri, Amir J; Groeschl, Michael; Lopez-Velasco, Gabriela; Hontecillas, Raquel

    2012-01-01

    There is an inverse secular trend between the incidence of obesity and gastric colonization with Helicobacter pylori, a bacterium that can affect the secretion of gastric hormones that relate to energy homeostasis. H. pylori strains that carry the cag pathogenicity island (PAI) interact more intimately with gastric epithelial cells and trigger more extensive host responses than cag(-) strains. We hypothesized that gastric colonization with H. pylori strains differing in cag PAI status exert distinct effects on metabolic and inflammatory phenotypes. To test this hypothesis, we examined metabolic and inflammatory markers in db/db mice and mice with diet-induced obesity experimentally infected with isogenic forms of H. pylori strain 26695: the cag PAI wild-type and its cag PAI mutant strain 99-305. H. pylori colonization decreased fasting blood glucose levels, increased levels of leptin, improved glucose tolerance, and suppressed weight gain. A response found in both wild-type and mutant H. pylori strain-infected mice included decreased white adipose tissue macrophages (ATM) and increased adipose tissue regulatory T cells (Treg) cells. Gene expression analyses demonstrated upregulation of gastric PPAR γ-responsive genes (i.e., CD36 and FABP4) in H. pylori-infected mice. The loss of PPAR γ in immune and epithelial cells in mice impaired the ability of H. pylori to favorably modulate glucose homeostasis and ATM infiltration during high fat feeding. Gastric infection with some commensal strains of H. pylori ameliorates glucose homeostasis in mice through a PPAR γ-dependent mechanism and modulates macrophage and Treg cell infiltration into the abdominal white adipose tissue.

  14. Helicobacter pylori colonization ameliorates glucose homeostasis in mice through a PPAR γ-dependent mechanism.

    Directory of Open Access Journals (Sweden)

    Josep Bassaganya-Riera

    Full Text Available BACKGROUND: There is an inverse secular trend between the incidence of obesity and gastric colonization with Helicobacter pylori, a bacterium that can affect the secretion of gastric hormones that relate to energy homeostasis. H. pylori strains that carry the cag pathogenicity island (PAI interact more intimately with gastric epithelial cells and trigger more extensive host responses than cag(- strains. We hypothesized that gastric colonization with H. pylori strains differing in cag PAI status exert distinct effects on metabolic and inflammatory phenotypes. METHODOLOGY/PRINCIPAL FINDINGS: To test this hypothesis, we examined metabolic and inflammatory markers in db/db mice and mice with diet-induced obesity experimentally infected with isogenic forms of H. pylori strain 26695: the cag PAI wild-type and its cag PAI mutant strain 99-305. H. pylori colonization decreased fasting blood glucose levels, increased levels of leptin, improved glucose tolerance, and suppressed weight gain. A response found in both wild-type and mutant H. pylori strain-infected mice included decreased white adipose tissue macrophages (ATM and increased adipose tissue regulatory T cells (Treg cells. Gene expression analyses demonstrated upregulation of gastric PPAR γ-responsive genes (i.e., CD36 and FABP4 in H. pylori-infected mice. The loss of PPAR γ in immune and epithelial cells in mice impaired the ability of H. pylori to favorably modulate glucose homeostasis and ATM infiltration during high fat feeding. CONCLUSIONS/SIGNIFICANCE: Gastric infection with some commensal strains of H. pylori ameliorates glucose homeostasis in mice through a PPAR γ-dependent mechanism and modulates macrophage and Treg cell infiltration into the abdominal white adipose tissue.

  15. Determination of glucose deficiency-induced cell death by mitochondrial ATP generation-driven proton homeostasis

    Institute of Scientific and Technical Information of China (English)

    Yanfen Cui; Yuanyuan Wang; Miao Liu; Li Qiu; Pan Xing; Xin Wang; Guoguang Ying; Binghui Li

    2017-01-01

    Glucose is one of major nutrients and its catabolism provides energy and/or building bricks for cell proliferation.Glucose deficiency results in cell death.However,the underlying mechanism still remains elusive.By using our recently developed method to monitor real-time cellular apoptosis and necrosis,we show that glucose deprivation can directly elicit necrosis,which is promoted by mitochondrial impairment,depending on mitochondrial adenosine triphosphate (ATP) generation instead of ATP depletion.We demonstrate that glucose metabolism is the major source to produce protons.Glucose deficiency leads to lack of proton provision while mitochondrial electron transfer chain continues consuming protons to generate energy,which provokes a compensatory iysosomal proton effiux and resultant increased lysosomal pH.This lysosomal alkalinization can trigger apoptosis or necrosis depending on the extent of alkalinization.Taken together,our results build up a metabolic connection between glycolysis,mitochondrion,and lysosome,and reveal an essential role of glucose metabolism in maintaining proton homeostasis to support cell survival.

  16. miR-182 Regulates Metabolic Homeostasis by Modulating Glucose Utilization in Muscle

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    Duo Zhang

    2016-07-01

    Full Text Available Understanding the fiber-type specification and metabolic switch in skeletal muscle provides insights into energy metabolism in physiology and diseases. Here, we show that miR-182 is highly expressed in fast-twitch muscle and negatively correlates with blood glucose level. miR-182 knockout mice display muscle loss, fast-to-slow fiber-type switching, and impaired glucose metabolism. Mechanistic studies reveal that miR-182 modulates glucose utilization in muscle by targeting FoxO1 and PDK4, which control fuel selection via the pyruvate dehydrogenase complex (PDHC. Short-term high-fat diet (HFD feeding reduces muscle miR-182 levels by tumor necrosis factor α (TNFα, which contributes to the upregulation of FoxO1/PDK4. Restoration of miR-182 expression in HFD-fed mice induces a faster muscle phenotype, decreases muscle FoxO1/PDK4 levels, and improves glucose metabolism. Together, our work establishes miR-182 as a critical regulator that confers robust and precise controls on fuel usage and glucose homeostasis. Our study suggests that a metabolic shift toward a faster and more glycolytic phenotype is beneficial for glucose control.

  17. MicroRNA-451 Negatively Regulates Hepatic Glucose Production and Glucose Homeostasis by Targeting Glycerol Kinase-Mediated Gluconeogenesis.

    Science.gov (United States)

    Zhuo, Shu; Yang, Mengmei; Zhao, Yanan; Chen, Xiaofang; Zhang, Feifei; Li, Na; Yao, Pengle; Zhu, Tengfei; Mei, Hong; Wang, Shanshan; Li, Yu; Chen, Shiting; Le, Yingying

    2016-11-01

    MicroRNAs (miRNAs) are a new class of regulatory molecules implicated in type 2 diabetes, which is characterized by insulin resistance and hepatic glucose overproduction. We show that miRNA-451 (miR-451) is elevated in the liver tissues of dietary and genetic mouse models of diabetes. Through an adenovirus-mediated gain- and loss-of-function study, we found that miR-451 negatively regulates hepatic gluconeogenesis and blood glucose levels in normal mice and identified glycerol kinase (Gyk) as a direct target of miR-451. We demonstrate that miR-451 and Gyk regulate hepatic glucose production, the glycerol gluconeogenesis axis, and the AKT-FOXO1-PEPCK/G6Pase pathway in an opposite manner; Gyk could reverse the effect of miR-451 on hepatic gluconeogenesis and AKT-FOXO1-PEPCK/G6Pase pathway. Moreover, overexpression of miR-451 or knockdown of Gyk in diabetic mice significantly inhibited hepatic gluconeogenesis, alleviated hyperglycemia, and improved glucose tolerance. Further studies showed that miR-451 is upregulated by glucose and insulin in hepatocytes; the elevation of hepatic miR-451 in diabetic mice may contribute to inhibiting Gyk expression. This study provides the first evidence that miR-451 and Gyk regulate the AKT-FOXO1-PEPCK/G6Pase pathway and play critical roles in hepatic gluconeogenesis and glucose homeostasis and identifies miR-451 and Gyk as potential therapeutic targets against hyperglycemia in diabetes. © 2016 by the American Diabetes Association.

  18. Cortical delta-opioid receptors potentiate K+ homeostasis during anoxia and oxygen-glucose deprivation.

    Science.gov (United States)

    Chao, Dongman; Donnelly, David F; Feng, Yin; Bazzy-Asaad, Alia; Xia, Ying

    2007-02-01

    Central neurons are extremely vulnerable to hypoxic/ischemic insult, which is a major cause of neurologic morbidity and mortality as a consequence of neuronal dysfunction and death. Our recent work has shown that delta-opioid receptor (DOR) is neuroprotective against hypoxic and excitotoxic stress, although the underlying mechanisms remain unclear. Because hypoxia/ischemia disrupts ionic homeostasis with an increase in extracellular K(+), which plays a role in neuronal death, we asked whether DOR activation preserves K(+) homeostasis during hypoxic/ischemic stress. To test this hypothesis, extracellular recordings with K(+)-sensitive microelectrodes were performed in mouse cortical slices under anoxia or oxygen-glucose deprivation (OGD). The main findings in this study are that (1) DOR activation with [D-Ala(2), D-Leu(5)]-enkephalinamide attenuated the anoxia- and OGD-induced increase in extracellular K(+) and decrease in DC potential in cortical slices; (2) DOR inhibition with naltrindole, a DOR antagonist, completely abolished the DOR-mediated prevention of increase in extracellular K(+) and decrease in DC potential; (3) inhibition of protein kinase A (PKA) with N-(2-[p-bromocinnamylamino]-ethyl)-5-isoquinolinesulfonamide dihydrochloride had no effect on the DOR protection; and (4) inhibition of protein kinase C (PKC) with chelerythrine chloride reduced the DOR protection, whereas the PKC activator (phorbol 12-myristate 13-acetate) mimicked the effect of DOR activation on K(+) homeostasis. These data suggest that activation of DOR protects the cortex against anoxia- or ODG-induced derangement of potassium homeostasis, and this protection occurs via a PKC-dependent and PKA-independent pathway. We conclude that an important aspect of DOR-mediated neuroprotection is its early action against derangement of K(+) homeostasis during anoxia or ischemia.

  19. Intermittent Hypoxia Impairs Glucose Homeostasis in C57BL6/J Mice: Partial Improvement with Cessation of the Exposure

    Science.gov (United States)

    Polak, Jan; Shimoda, Larissa A.; Drager, Luciano F.; Undem, Clark; McHugh, Holly; Polotsky, Vsevolod Y.; Punjabi, Naresh M.

    2013-01-01

    Objectives: Obstructive sleep apnea is associated with insulin resistance, glucose intolerance, and type 2 diabetes mellitus. Although several studies have suggested that intermittent hypoxia in obstructive sleep apnea may induce abnormalities in glucose homeostasis, it remains to be determined whether these abnormalities improve after discontinuation of the exposure. The objective of this study was to delineate the effects of intermittent hypoxia on glucose homeostasis, beta cell function, and liver glucose metabolism and to investigate whether the impairments improve after the hypoxic exposure is discontinued. Interventions: C57BL6/J mice were exposed to 14 days of intermittent hypoxia, 14 days of intermittent air, or 7 days of intermittent hypoxia followed by 7 days of intermittent air (recovery paradigm). Glucose and insulin tolerance tests were performed to estimate whole-body insulin sensitivity and calculate measures of beta cell function. Oxidative stress in pancreatic tissue and glucose output from isolated hepatocytes were also assessed. Results: Intermittent hypoxia increased fasting glucose levels and worsened glucose tolerance by 67% and 27%, respectively. Furthermore, intermittent hypoxia exposure was associated with impairments in insulin sensitivity and beta cell function, an increase in liver glycogen, higher hepatocyte glucose output, and an increase in oxidative stress in the pancreas. While fasting glucose levels and hepatic glucose output normalized after discontinuation of the hypoxic exposure, glucose intolerance, insulin resistance, and impairments in beta cell function persisted. Conclusions: Intermittent hypoxia induces insulin resistance, impairs beta cell function, enhances hepatocyte glucose output, and increases oxidative stress in the pancreas. Cessation of the hypoxic exposure does not fully reverse the observed changes in glucose metabolism. Citation: Polak J; Shimoda LA; Drager LF; Undem C; McHugh H; Polotsky VY; Punjabi NM

  20. Ambient air pollution, adipokines, and glucose homeostasis: The Framingham Heart Study.

    Science.gov (United States)

    Li, Wenyuan; Dorans, Kirsten S; Wilker, Elissa H; Rice, Mary B; Kloog, Itai; Schwartz, Joel D; Koutrakis, Petros; Coull, Brent A; Gold, Diane R; Meigs, James B; Fox, Caroline S; Mittleman, Murray A

    2018-02-01

    To examine associations of proximity to major roadways, sustained exposure to fine particulate matter (PM 2.5 ), and acute exposure to ambient air pollutants with adipokines and measures of glucose homeostasis among participants living in the northeastern United States. We included 5958 participants from the Framingham Offspring cohort examination cycle 7 (1998-2001) and 8 (2005-2008) and Third Generation cohort examination cycle 1 (2002-2005) and 2 (2008-2011), who did not have type 2 diabetes at the time of examination visit. We calculated 2003 annual average PM 2.5 at participants' home address, residential distance to the nearest major roadway, and daily PM 2.5 , black carbon (BC), sulfate, nitrogen oxides (NO x ), and ozone concentrations. We used linear mixed effects models for fasting glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) which were measured up to twice, and used linear regression models for adiponectin, resistin, leptin, and hemoglobin A1c (HbA1c) which were measured only once, adjusting for demographics, socioeconomic position, lifestyle, time, and seasonality. The mean age was 51years and 55% were women. Participants who lived 64m (25th percentile) from a major roadway had 0.28% (95% CI: 0.05%, 0.51%) higher fasting plasma glucose than participants who lived 413m (75th percentile) away, and the association appeared to be driven by participants who lived within 50m from a major roadway. Higher exposures to 3- to 7-day moving averages of BC and NO x were associated with higher glucose whereas the associations for ozone were negative. The associations otherwise were generally null and did not differ by median age, sex, educational attainment, obesity status, or prediabetes status. Living closer to a major roadway or acute exposure to traffic-related air pollutants were associated with dysregulated glucose homeostasis but not with adipokines among participants from the Framingham Offspring and Third Generation

  1. Transient Receptor Potential Canonical 3 (TRPC3) Channels Are Required for Hypothalamic Glucose Detection and Energy Homeostasis.

    Science.gov (United States)

    Chrétien, Chloé; Fenech, Claire; Liénard, Fabienne; Grall, Sylvie; Chevalier, Charlène; Chaudy, Sylvie; Brenachot, Xavier; Berges, Raymond; Louche, Katie; Stark, Romana; Nédélec, Emmanuelle; Laderrière, Amélie; Andrews, Zane B; Benani, Alexandre; Flockerzi, Veit; Gascuel, Jean; Hartmann, Jana; Moro, Cédric; Birnbaumer, Lutz; Leloup, Corinne; Pénicaud, Luc; Fioramonti, Xavier

    2017-02-01

    The mediobasal hypothalamus (MBH) contains neurons capable of directly detecting metabolic signals such as glucose to control energy homeostasis. Among them, glucose-excited (GE) neurons increase their electrical activity when glucose rises. In view of previous work, we hypothesized that transient receptor potential canonical type 3 (TRPC3) channels are involved in hypothalamic glucose detection and the control of energy homeostasis. To investigate the role of TRPC3, we used constitutive and conditional TRPC3-deficient mouse models. Hypothalamic glucose detection was studied in vivo by measuring food intake and insulin secretion in response to increased brain glucose level. The role of TRPC3 in GE neuron response to glucose was studied by using in vitro calcium imaging on freshly dissociated MBH neurons. We found that whole-body and MBH TRPC3-deficient mice have increased body weight and food intake. The anorectic effect of intracerebroventricular glucose and the insulin secretory response to intracarotid glucose injection are blunted in TRPC3-deficient mice. TRPC3 loss of function or pharmacological inhibition blunts calcium responses to glucose in MBH neurons in vitro. Together, the results demonstrate that TRPC3 channels are required for the response to glucose of MBH GE neurons and the central effect of glucose on insulin secretion and food intake. © 2017 by the American Diabetes Association.

  2. Zinc Status Affects Glucose Homeostasis and Insulin Secretion in Patients with Thalassemia

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    Ellen B. Fung

    2015-06-01

    Full Text Available Up to 20% of adult patients with Thalassemia major (Thal live with diabetes, while 30% may be zinc deficient. The objective of this study was to explore the relationship between zinc status, impaired glucose tolerance and insulin sensitivity in Thal patients. Charts from thirty subjects (16 male, 27.8 ± 9.1 years with Thal were reviewed. Patients with low serum zinc had significantly lower fasting insulin, insulinogenic and oral disposition indexes (all p < 0.05 and elevated glucose response curve, following a standard 75 g oral load of glucose compared to those with normal serum zinc after controlling for baseline (group × time interaction p = 0.048. Longitudinal data in five patients with a decline in serum zinc over a two year follow up period (−19.0 ± 9.6 μg/dL, showed consistent increases in fasting glucose (3.6 ± 3.2 mg/dL and insulin to glucose ratios at 120 min post glucose dose (p = 0.05. Taken together, these data suggest that the frequently present zinc deficiency in Thal patients is associated with decreased insulin secretion and reduced glucose disposal. Future zinc trials will require modeling of oral glucose tolerance test data and not simply measurement of static indices in order to understand the complexities of pancreatic function in the Thal patient.

  3. Impaired glucose homeostasis in non-diabetic Greek hypertensives with diabetes family history. Effect of the obesity status.

    Science.gov (United States)

    Vyssoulis, Gregory P; Liakos, Charalampos I; Karpanou, Eva A; Triantafyllou, Athanasios I; Michaelides, Andreas P; Tzamou, Vanessa E; Markou, Maria I; Stefanadis, Christodoulos I

    2013-01-01

    Arterial hypertension (AH) and diabetes mellitus (DM) are established cardiovascular risk factors. Impaired glucose homeostasis (IGH; impaired fasting glucose or/and impaired glucose tolerance) or pre-diabetes, obesity, and DM family history identify individuals at risk for type 2 DM in whom preventive interventions are necessary. The aim of this study was to determine the glycemic profile in non-diabetic Greek adult hypertensive men and women according to DM family history and the obesity status. Diabetes family history, obesity markers (waist-to-hip ratio, WHR; body mass index, BMI), glycemic parameters (fasting and 2-hour post-load plasma glucose, if necessary; glycated hemoglobin, HbA1c; fasting insulin), insulin resistance indices (homeostasis model assessment, HOMA; quantitative insulin sensitivity check index, QUICKI; Bennett; McAuley), and IGH prevalence were determined in a large cohort of 11,540 Greek hypertensives referred to our institutions. Positive DM family history was associated with elevated fasting glucose (98.6 ± 13.1 vs 96.5 ± 12.3 mg/dL), HbA1c (5.58% ± 0.49% vs 5.50% ± 0.46%), fasting insulin (9.74 ± 4.20 vs 9.21 ± 3.63 μU/mL) and HOMA (2.43 ± 1.19 vs 2.24 ± 1.01) values, lower QUICKI (0.342 ± 0.025 vs 0.345 ± 0.023), Bennett (0.285 ± 0.081 vs 0.292 ± 0.078) and McAuley (6.73 ± 3.43 vs 6.95 ± 3.44) values, and higher IGH prevalence (45.3% vs 38.7%); P history was significant (P history present with higher IGH prevalence and worse glycemic indices levels compared with those with negative family history, especially in the higher WHR/BMI subgroups. Copyright © 2013 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

  4. Glucose Homeostasis, Pancreatic Endocrine Function, and Outcomes in Advanced Heart Failure.

    Science.gov (United States)

    Melenovsky, Vojtech; Benes, Jan; Franekova, Janka; Kovar, Jan; Borlaug, Barry A; Segetova, Marketa; Tura, Andrea; Pelikanova, Tereza

    2017-08-07

    The mechanisms and relevance of impaired glucose homeostasis in advanced heart failure (HF) are poorly understood. The study goals were to examine glucose regulation, pancreatic endocrine function, and metabolic factors related to prognosis in patients with nondiabetic advanced HF. In total, 140 advanced HF patients without known diabetes mellitus and 21 sex-, age-, and body mass index-matched controls underwent body composition assessment, oral glucose tolerance testing, and measurement of glucose-regulating hormones to model pancreatic β-cell secretory response. Compared with controls, HF patients had similar fasting glucose and insulin levels but higher levels after oral glucose tolerance testing. Insulin secretion was not impaired, but with increasing HF severity, there was a reduction in glucose, insulin, and insulin/glucagon ratio-a signature of starvation. The insulin/C-peptide ratio was decreased in HF, indicating enhanced insulin clearance, and this was correlated with lower cardiac output, hepatic insufficiency, right ventricular dysfunction, and body wasting. After a median of 449 days, 41% of patients experienced an adverse event (death, urgent transplant, or assist device). Increased glucagon and, paradoxically, low fasting plasma glucose displayed the strongest relations to outcome ( P =0.01). Patients in the lowest quartile of fasting plasma glucose (3.8-5.1 mmol·L -1 , 68-101 mg·dL -1 ) had 3-times higher event risk than in the top quartile (6.0-7.9 mmol·L -1 , 108-142 mg·dL -1 ; relative risk: 3.05 [95% confidence interval, 1.46-6.77]; P =0.002). Low fasting plasma glucose and increased glucagon are robust metabolic predictors of adverse events in advanced HF. Pancreatic insulin secretion is preserved in advanced HF, but levels decrease with increasing HF severity due to enhanced insulin clearance that is coupled with right heart failure and cardiac cachexia. © 2017 The Authors. Published on behalf of the American Heart Association, Inc

  5. Glucose homeostasis in Egyptian children and adolescents with β-Thalassemia major: Relationship to oxidative stress

    Directory of Open Access Journals (Sweden)

    Kotb Abbass Metwalley

    2014-01-01

    Full Text Available Background: Oxidative stress in children with β-thalassemia may contribute to shortened life span of erythrocytes and endocrinal abnormalities. Aim: This study was aimed to evaluate glucose homeostasis in Egyptian children and adolescents with β-thalassemia major and its relation to oxidative stress. Materials and Methods: Sixty children and adolescents with β-thalassemia major were studied in comparison to 30 healthy age and sex-matched subjects. Detailed medical history, thorough clinical examination, and laboratory assessment of oral glucose tolerance test (OGTT, serum ferritin, alanine transferase (ALT, fasting insulin levels, plasma malondialdehyde (MDA as oxidant marker and serum total antioxidants capacity (TAC were performed. Patients were divided into two groups according to the presence of abnormal OGTT. Results: The prevalence of diabetes was 5% (3 of 60 and impaired glucose tolerance test (IGT was 8% (5 of 60. Fasting blood glucose, 2-hour post-load plasma glucose, serum ferritin, ALT, fasting insulin level, homeostatic model assessment for insulin resistance index (HOMA-IR and MDA levels were significantly elevated while TAC level was significantly decreased in thalassemic patients compared with healthy controls (P < 0.001 for each. The difference was more evident in patients with abnormal OGTT than those with normal oral glucose tolerance (P < 0.001 for each. We also observed that thalassemic patients not receiving or on irregular chelation therapy had significantly higher fasting, 2-h post-load plasma glucose, serum ferritin, ALT, fasting insulin, HOMA-IR, oxidative stress markers OSI and MDA levels and significantly lower TAC compared with either those on regular chelation or controls. HOMA-IR was positively correlated with age, serum ferritin, ALT, MDA, and negatively correlated with TAC. Conclusions: The development of abnormal glucose tolerance in Egyptian children and adolescents with β--thalassemia is associated with

  6. Perfluorooctanoic acid exposure for 28 days affects glucose homeostasis and induces insulin hypersensitivity in mice

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    Yan, Shengmin; Zhang, Hongxia; Zheng, Fei; Sheng, Nan; Guo, Xuejiang; Dai, Jiayin

    2015-06-01

    Perfluoroalkyl acids (PFAAs) are widely used in many applications due to their unique physical and chemical characteristics. Because of the increasing prevalence of metabolic syndromes, including obesity, dyslipidemia and insulin resistance, concern has arisen about the roles of environmental pollutants in such diseases. Earlier epidemiologic studies showed a potential association between perfluorooctanoic acid (PFOA) and glucose metabolism, but how PFOA influences glucose homeostasis is still unknown. Here, we report on the modulation of the phosphatidylinositol 3-kinase-serine/threonine protein kinase (PI3K-AKT) signaling pathway in the livers of mice after 28 d of exposure to PFOA. Compared with normal mice, PFOA exposure significantly decreased the expression of the phosphatase and tensin homologue (PTEN) protein and affected the PI3K-AKT signaling pathway in the liver. Tolerance tests further indicated that PFOA exposure induced higher insulin sensitivity and glucose tolerance in mice. Biochemical analysis revealed that PFOA exposure reduced hepatic glycogen synthesis, which might be attributed to gluconeogenesis inhibition. The levels of several circulating proteins were altered after PFOA exposure, including proteins potentially related to diabetes and liver disease. Our results suggest that PFOA affected glucose metabolism and induced insulin hypersensitivity in mice.

  7. Beneficial effects of banana leaves (Musa x paradisiaca on glucose homeostasis: multiple sites of action

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    Virginia D. Kappel

    2013-09-01

    Full Text Available The acute effect of crude extract, n-butanol and aqueous residual fractions of Musa x paradisiaca L., Musaceae, leaves on glycemia, serum insulin secretion and glycogen content in an in vivo approach was evaluated. In addition, the in vitro effect on disaccharidases activity and albumin glycation was studied. The crude extract and fractions, n-butanol and aqueous residual, reduced glycemia and increased liver glycogen content in hyperglycemic rats, inhibited maltase activity and the formation of advanced glycation end-products in vitro. Also, a significant increase in insulin secretion and muscle glycogen content in hyperglycemic rats was observed with oral administration of the n-butanol fraction. Phytochemical analysis demonstrated the presence of rutin in crude extract and fractions of M. x paradisiaca leaves as the major compound. These beneficial effects on the regulation of glucose homeostasis observed for M. x paradisiaca leaves and the presence of rutin as the major compound indicate potential anti-diabetic properties, since previous studies have been reported that rutin can modulate glucose homeostasis.

  8. Metabolomic profiling identifies potential pathways involved in the interaction of iron homeostasis with glucose metabolism

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    Lars Stechemesser

    2017-01-01

    Full Text Available Objective: Elevated serum ferritin has been linked to type 2 diabetes (T2D and adverse health outcomes in subjects with the Metabolic Syndrome (MetS. As the mechanisms underlying the negative impact of excess iron have so far remained elusive, we aimed to identify potential links between iron homeostasis and metabolic pathways. Methods: In a cross-sectional study, data were obtained from 163 patients, allocated to one of three groups: (1 lean, healthy controls (n = 53, (2 MetS without hyperferritinemia (n = 54 and (3 MetS with hyperferritinemia (n = 56. An additional phlebotomy study included 29 patients with biopsy-proven iron overload before and after iron removal. A detailed clinical and biochemical characterization was obtained and metabolomic profiling was performed via a targeted metabolomics approach. Results: Subjects with MetS and elevated ferritin had higher fasting glucose (p < 0.001, HbA1c (p = 0.035 and 1 h glucose in oral glucose tolerance test (p = 0.002 compared to MetS subjects without iron overload, whereas other clinical and biochemical features of the MetS were not different. The metabolomic study revealed significant differences between MetS with high and low ferritin in the serum concentrations of sarcosine, citrulline and particularly long-chain phosphatidylcholines. Methionine, glutamate, and long-chain phosphatidylcholines were significantly different before and after phlebotomy (p < 0.05 for all metabolites. Conclusions: Our data suggest that high serum ferritin concentrations are linked to impaired glucose homeostasis in subjects with the MetS. Iron excess is associated to distinct changes in the serum concentrations of phosphatidylcholine subsets. A pathway involving sarcosine and citrulline also may be involved in iron-induced impairment of glucose metabolism. Author Video: Author Video Watch what authors say about their articles Keywords: Metabolomics, Hyperferritinemia, Iron overload, Metabolic

  9. Sex-Related Differences in the Effects of the Mediterranean Diet on Glucose and Insulin Homeostasis

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    Alexandra Bédard

    2014-01-01

    Full Text Available Objective. To document sex differences in the impact of the Mediterranean diet (MedDiet on glucose/insulin homeostasis and to verify whether these sex-related effects were associated with changes in nonesterified fatty acids (NEFA. Methods. All foods were provided to 38 men and 32 premenopausal women (24–53 y during 4 weeks. Variables were measured during a 180 min OGTT before and after the MedDiet. Results. A sex-by-time interaction for plasma insulin iAUC was found (men: −17.8%, P=0.02; women: +9.4%, P=0.63; P for sex-by-time interaction = 0.005. A sex-by-time interaction was also observed for insulin sensitivity (Cederholm index, P=0.03, for which only men experienced improvements (men: +8.1%, P=0.047; women: −5.9%, P=0.94. No sex difference was observed for glucose and C-peptide responses. Trends toward a decrease in NEFA AUC (P=0.06 and an increase in NEFA suppression rate (P=0.06 were noted, with no sex difference. Changes in NEFA were not associated with change in insulin sensitivity. Conclusions. Results suggest that the more favorable changes in glucose/insulin homeostasis observed in men compared to women in response to the MedDiet are not explained by sex differences in NEFA response. This clinical trial is registered with clinicaltrials.gov NCT01293344.

  10. Sex-Related Differences in the Effects of the Mediterranean Diet on Glucose and Insulin Homeostasis

    Science.gov (United States)

    Bédard, Alexandra; Corneau, Louise; Lamarche, Benoît; Dodin, Sylvie; Lemieux, Simone

    2014-01-01

    Objective. To document sex differences in the impact of the Mediterranean diet (MedDiet) on glucose/insulin homeostasis and to verify whether these sex-related effects were associated with changes in nonesterified fatty acids (NEFA). Methods. All foods were provided to 38 men and 32 premenopausal women (24–53 y) during 4 weeks. Variables were measured during a 180 min OGTT before and after the MedDiet. Results. A sex-by-time interaction for plasma insulin iAUC was found (men: −17.8%, P = 0.02; women: +9.4%, P = 0.63; P for sex-by-time interaction = 0.005). A sex-by-time interaction was also observed for insulin sensitivity (Cederholm index, P = 0.03), for which only men experienced improvements (men: +8.1%, P = 0.047; women: −5.9%, P = 0.94). No sex difference was observed for glucose and C-peptide responses. Trends toward a decrease in NEFA AUC (P = 0.06) and an increase in NEFA suppression rate (P = 0.06) were noted, with no sex difference. Changes in NEFA were not associated with change in insulin sensitivity. Conclusions. Results suggest that the more favorable changes in glucose/insulin homeostasis observed in men compared to women in response to the MedDiet are not explained by sex differences in NEFA response. This clinical trial is registered with clinicaltrials.gov NCT01293344. PMID:25371817

  11. Enhanced leptin sensitivity and improved glucose homeostasis in mice lacking suppressor of cytokine signaling-3 in POMC-expressing cells.

    Science.gov (United States)

    Kievit, Paul; Howard, Jane K; Badman, Michael K; Balthasar, Nina; Coppari, Roberto; Mori, Hiroyuki; Lee, Charlotte E; Elmquist, Joel K; Yoshimura, Akihiko; Flier, Jeffrey S

    2006-08-01

    Suppressor of cytokine signaling-3 (Socs-3) negatively regulates the action of various cytokines, as well as the metabolic hormones leptin and insulin. Mice with haploinsufficiency of Socs-3, or those with neuronal deletion of Socs-3, are lean and more leptin and insulin sensitive. To examine the role of Socs-3 within specific neurons critical to energy balance, we created mice with selective deletion of Socs-3 within pro-opiomelanocortin (POMC)-expressing cells. These mice had enhanced leptin sensitivity, measured by weight loss and food intake after leptin infusion. On chow diet, glucose homeostasis was improved despite normal weight gain. On a high-fat diet, the rate of weight gain was reduced, due to increased energy expenditure rather than decreased food intake; glucose homeostasis and insulin sensitivity were substantially improved. These studies demonstrate that Socs-3 within POMC neurons regulates leptin sensitivity and glucose homeostasis, and plays a key role in linking high-fat diet to disordered metabolism.

  12. The Contribution of Intestinal Gluconeogenesis to Glucose Homeostasis Is Low in 2-Day-Old Pigs.

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    Cherbuy, Claire; Vaugelade, Pierre; Labarthe, Simon; Honvo-Houeto, Edith; Darcy-Vrillon, Béatrice; Watford, Malcolm; Duée, Pierre-Henri

    2017-03-01

    Background: Active gluconeogenesis is essential to maintain blood glucose concentrations in neonatal piglets because of the high glucose requirements after birth. In several adult mammals, the liver, kidney, and possibly the gut may exhibit gluconeogenesis during fasting and insulinopenic conditions. During the postnatal period, the intestine expresses all of the gluconeogenic enzymes, suggesting the potential for gluconeogenesis. Galactose in milk is a potential gluconeogenic precursor for newborns. Objective: Our aim was to quantify the rate of intestinal glucose production from galactose in piglets compared with the overall rate of glucose production. Methods: A single bolus of [U- 14 C]-galactose was injected into 2-d-old piglets (females and males; mean ± SEM weight: 1.64 ± 0.07 kg) through a gastric catheter. Galactosemia, glycemia, and glucose turnover rate (assessed by monitoring d-[6- 3 H]-glucose) were monitored. Intestinal glucose production from [U- 14 C]-galactose was calculated from [U- 14 C]-glucose appearance in the blood and isotopic dilution. Galactose metabolism was also investigated in vitro in enterocytes isolated from 2-d-old piglets that were incubated with increasing concentrations of galactose. Results: In piglet enterocytes, galactose metabolism was active (mean ± SEM maximum rate of reaction: 2.26 ± 0.45 nmol · min -1 · 10 6 cells -1 ) and predominantly oriented toward lactate and pyruvate production (74.0% ± 14.5%) rather than glucose production (26.0% ± 14.5%). In conscious piglets, gastric galactose administration led to an increase in arterial galactosemia (from 0 to 1.0 ± 0.8 mmol/L) and glycemia (35% ± 12%). The initial increase in arterial glycemia after galactose administration was linked to an increase in glucose production rate (33% ± 15%) rather than to a decrease in glucose utilization rate (3% ± 6%). The contribution of intestinal glucose production from galactose was gluconeogenesis in 2-d-old piglets. © 2017

  13. Intermittent hypoxia impairs glucose homeostasis in C57BL6/J mice: partial improvement with cessation of the exposure.

    Science.gov (United States)

    Polak, Jan; Shimoda, Larissa A; Drager, Luciano F; Undem, Clark; McHugh, Holly; Polotsky, Vsevolod Y; Punjabi, Naresh M

    2013-10-01

    Obstructive sleep apnea is associated with insulin resistance, glucose intolerance, and type 2 diabetes mellitus. Although several studies have suggested that intermittent hypoxia in obstructive sleep apnea may induce abnormalities in glucose homeostasis, it remains to be determined whether these abnormalities improve after discontinuation of the exposure. The objective of this study was to delineate the effects of intermittent hypoxia on glucose homeostasis, beta cell function, and liver glucose metabolism and to investigate whether the impairments improve after the hypoxic exposure is discontinued. C57BL6/J mice were exposed to 14 days of intermittent hypoxia, 14 days of intermittent air, or 7 days of intermittent hypoxia followed by 7 days of intermittent air (recovery paradigm). Glucose and insulin tolerance tests were performed to estimate whole-body insulin sensitivity and calculate measures of beta cell function. Oxidative stress in pancreatic tissue and glucose output from isolated hepatocytes were also assessed. Intermittent hypoxia increased fasting glucose levels and worsened glucose tolerance by 67% and 27%, respectively. Furthermore, intermittent hypoxia exposure was associated with impairments in insulin sensitivity and beta cell function, an increase in liver glycogen, higher hepatocyte glucose output, and an increase in oxidative stress in the pancreas. While fasting glucose levels and hepatic glucose output normalized after discontinuation of the hypoxic exposure, glucose intolerance, insulin resistance, and impairments in beta cell function persisted. Intermittent hypoxia induces insulin resistance, impairs beta cell function, enhances hepatocyte glucose output, and increases oxidative stress in the pancreas. Cessation of the hypoxic exposure does not fully reverse the observed changes in glucose metabolism.

  14. Dimethyl amiloride improves glucose homeostasis in mouse models of type 2 diabetes.

    Science.gov (United States)

    Gunawardana, Subhadra C; Head, W Steven; Piston, David W

    2008-06-01

    Dimethyl amiloride (DMA) enhances insulin secretion in the pancreatic beta-cell. DMA also enhances time-dependent potentiation (TDP) and enables TDP to occur in situations where it is normally absent. As we have demonstrated before, these effects are mediated in part through inhibition of neuronal nitric oxide synthase (nNOS), resulting in increased availability of arginine. Thus both DMA and arginine have the potential to correct the secretory defect in diabetes by enabling or enhancing TDP. In the current study we have demonstrated the ability of these agents to improve blood glucose homeostasis in three mouse models of type 2 diabetes. The pattern of TDP under different conditions indicates that inhibition of NOS is not the only mechanism through which DMA exerts its positive effects. Thus we also have explored another possible mechanism through which DMA enables/enhances TDP, via the activation of mitochondrial alpha-ketoglutarate dehydrogenase.

  15. Central control of glucose homeostasis: the brain--endocrine pancreas axis.

    Science.gov (United States)

    Thorens, B

    2010-10-01

    A large body of data gathered over the last decades has delineated the neuronal pathways that link the central nervous system with the autonomic innervation of the endocrine pancreas, which controls alpha- and beta-cell secretion activity and mass. These are important regulatory functions that are certainly keys for preserving the capacity of the endocrine pancreas to control glucose homeostasis over a lifetime. Identifying the cells involved in controlling the autonomic innervation of the endocrine pancreas, in response to nutrient, hormonal and environmental cues and how these cues are detected to activate neuronal activity are important goals of current research. Elucidation of these questions may possibly lead to new means for preserving or restoring defects in insulin and glucagon secretion associated with type 2 diabetes. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  16. Sensing the fuels: glucose and lipid signaling in the CNS controlling energy homeostasis.

    Science.gov (United States)

    Jordan, Sabine D; Könner, A Christine; Brüning, Jens C

    2010-10-01

    The central nervous system (CNS) is capable of gathering information on the body's nutritional state and it implements appropriate behavioral and metabolic responses to changes in fuel availability. This feedback signaling of peripheral tissues ensures the maintenance of energy homeostasis. The hypothalamus is a primary site of convergence and integration for these nutrient-related feedback signals, which include central and peripheral neuronal inputs as well as hormonal signals. Increasing evidence indicates that glucose and lipids are detected by specialized fuel-sensing neurons that are integrated in these hypothalamic neuronal circuits. The purpose of this review is to outline the current understanding of fuel-sensing mechanisms in the hypothalamus, to integrate the recent findings in this field, and to address the potential role of dysregulation in these pathways in the development of obesity and type 2 diabetes mellitus.

  17. Revisiting “Vegetables” to combat modern epidemic of imbalanced glucose homeostasis

    Science.gov (United States)

    Tiwari, Ashok Kumar

    2014-01-01

    Vegetables have been part of human food since prehistoric times and are considered nutritionally necessary and good for health. Vegetables are rich natural resource of biological antioxidants and possess capabilities of maintaining glucose homeostasis. When taken before starch-rich diet, juice also of vegetables such as ridge gourd, bottle gourd, ash gourd, chayote and juice of leaves of vegetables such as radish, Indian Dill, ajwain, tropical green amaranth, and bladder dock are reported to arrest significantly the rise in postprandial blood glucose level. Juice of vegetables such as ash gourd, squash gourd, and tropical green amaranth leaves are observed to tone-down sweet-beverages such as sucrose, fructose, and glucose-induced postprandial glycemic excursion. On the other hand, juice of egg-plant and juice of leaves of Ceylon spinach, Joyweed, and palak are reported to augment starch-induced postprandial glycemic excursion; and juice of leaves of Ceylon spinach, Joyweed, and radish supplement to the glucose-induced postprandial glycemia. Vegetables possess multifaceted antihyperglycemic activities such as inhibition of pancreatic α-amylase and intestinal α-glucosidase, inhibition of protein-tyrosine phosphatase 1β in liver and skeletal muscles, and insulin mimetic and secretagogue activities. Furthermore, they are also reported to influence polyol pathway in favor of reducing development of oxidative stress, and consequently the development of diabetic complications. In the wake of emergence of modern maladaptive diet-induced hyperglycemic epidemic therefore, vegetables may offer cost-effective dietary regimen to control diet-induced glycemic over load and future development of diabetes mellitus. However, for vegetables have been reported to do both, mitigate as well as supplement to the diet-induced postprandial glycemic load, care is required in selection of vegetables when considered as medicament. PMID:24991093

  18. Pancreatic alpha-cell dysfunction contributes to the disruption of glucose homeostasis and compensatory insulin hypersecretion in glucocorticoid-treated rats.

    Directory of Open Access Journals (Sweden)

    Alex Rafacho

    Full Text Available Glucocorticoid (GC-based therapies can cause insulin resistance (IR, glucose intolerance, hyperglycemia and, occasionally, overt diabetes. Understanding the mechanisms behind these metabolic disorders could improve the management of glucose homeostasis in patients undergoing GC treatment. For this purpose, adult rats were treated with a daily injection of dexamethasone (1 mg/kg b.w., i.p. (DEX or saline as a control for 5 consecutive days. The DEX rats developed IR, augmented glycemia, hyperinsulinemia and hyperglucagonemia. Treatment of the DEX rats with a glucagon receptor antagonist normalized their blood glucose level. The characteristic inhibitory effect of glucose on glucagon secretion was impaired in the islets of the DEX rats, while no direct effects were found on α-cells in islets that were incubated with DEX in vitro. A higher proportion of docked secretory granules was found in the DEX α-cells as well as a trend towards increased α-cell mass. Additionally, insulin secretion in the presence of glucagon was augmented in the islets of the DEX rats, which was most likely due to their higher glucagon receptor content. We also found that the enzyme 11βHSD-1, which participates in GC metabolism, contributed to the insulin hypersecretion in the DEX rats under basal glucose conditions. Altogether, we showed that GC treatment induces hyperglucagonemia, which contributes to an imbalance in glucose homeostasis and compensatory β-cell hypersecretion. This hyperglucagonemia may result from altered α-cell function and, likely, α-cell mass. Additionally, blockage of the glucagon receptor seems to be effective in preventing the elevation in blood glucose levels induced by GC administration.

  19. A systematic review and meta-analysis of the impact of mineralocorticoid receptor antagonists on glucose homeostasis

    OpenAIRE

    Korol, Sandra; Mottet, Fannie; Perreault, Sylvie; Baker, William L.; White, Michel; de Denus, Simon

    2017-01-01

    Abstract Background: Spironolactone, a nonselective mineralocorticoid receptor antagonist (MRA), may have a deleterious effect on glycemia. The objective of this review was to assess current knowledge on MRAs’ influence (spironolactone, eplerenone, and canrenone) on glucose homeostasis and the risk of diabetes. Method: A systematic review was conducted using the Medline database on articles published from 1946 to January 2017 that studied the effects of MRAs on any glucose-related endpoints, ...

  20. The CNS glucagon-like peptide-2 receptor in the control of energy balance and glucose homeostasis

    Science.gov (United States)

    2014-01-01

    The gut-brain axis plays a key role in the control of energy balance and glucose homeostasis. In response to luminal stimulation of macronutrients and microbiota-derived metabolites (secondary bile acids and short chain fatty acids), glucagon-like peptides (GLP-1 and -2) are cosecreted from endocrine L cells in the gut and coreleased from preproglucagonergic neurons in the brain stem. Glucagon-like peptides are proposed as key mediators for bariatric surgery-improved glycemic control and energy balance. Little is known about the GLP-2 receptor (Glp2r)-mediated physiological roles in the control of food intake and glucose homeostasis, yet Glp1r has been studied extensively. This review will highlight the physiological relevance of the central nervous system (CNS) Glp2r in the control of energy balance and glucose homeostasis and focuses on cellular mechanisms underlying the CNS Glp2r-mediated neural circuitry and intracellular PI3K signaling pathway. New evidence (obtained from Glp2r tissue-specific KO mice) indicates that the Glp2r in POMC neurons is essential for suppressing feeding behavior, gastrointestinal motility, and hepatic glucose production. Mice with Glp2r deletion selectively in POMC neurons exhibit hyperphagic behavior, accelerated gastric emptying, glucose intolerance, and hepatic insulin resistance. GLP-2 differentially modulates postsynaptic membrane excitability of hypothalamic POMC neurons in Glp2r- and PI3K-dependent manners. GLP-2 activates the PI3K-Akt-FoxO1 signaling pathway in POMC neurons by Glp2r-p85α interaction. Intracerebroventricular GLP-2 augments glucose tolerance, suppresses glucose production, and enhances insulin sensitivity, which require PI3K (p110α) activation in POMC neurons. Thus, the CNS Glp2r plays a physiological role in the control of food intake and glucose homeostasis. This review will also discuss key questions for future studies. PMID:24990862

  1. Glucose homeostasis in the intensive care: the end of a cycle

    LENUS (Irish Health Repository)

    Murphy, JFA

    2012-10-01

    Over the last decade there has been extensive literature and debate about blood glucose control in adults and children undergoing intensive care. The concept of tight glycaemic management began in adults and subsequently trickled down to paediatric patients. Hyperglycaemia is known to correlate with the degree of organ failure and death. The central question is whether hyperglycaemia is simply a marker of illness severity or a contributory factor in the patient’s illness. This is of fundamental importance in that it determines whether one should intervene or defer insulin treatment. The other issue is whether treatment with insulin is beneficial or harmful in this ICU setting. Possible explanations for the adverse effects of high glucose include pro-inflammatory responses. It was postulated that lethal perfusion injury to vital organs could be reduced by the prevention of hyperglycaemia with insulin. It was clear that randomised trials were needed to determine the best course of action.

  2. Assessment of glucose homeostasis in crossbred steer progeny sired by Brahman bulls that experienced prenatal transportation stress

    Science.gov (United States)

    The objective of this experiment was to assess glucose homeostasis of crossbred male progeny whose Brahman sires experienced prenatal transportation stress (PS) in utero. Sixteen steers (PNS group) sired by 3 PS bulls gestating dams were transported for 2 h at 60, 80, 100, 120, and 140 ± 5 d of gest...

  3. A low-protein diet combined with low-dose endotoxin leads to changes in glucose homeostasis in weanling rats

    NARCIS (Netherlands)

    Bandsma, Robert H. J.; Ackerley, Cameron; Koulajian, Khajag; Zhang, Ling; van Zutphen, Tim; van Dijk, Theo H.; Xiao, Changting; Giacca, Adria; Lewis, Gary F.

    2015-01-01

    Severe malnutrition is a leading cause of global childhood mortality, and infection and hypoglycemia or hyperglycemia are commonly present. The etiology behind the changes in glucose homeostasis is poorly understood. Here, we generated an animal model of severe malnutrition with and without

  4. Deletion of hepatic carbohydrate response element binding protein (ChREBP impairs glucose homeostasis and hepatic insulin sensitivity in mice

    Directory of Open Access Journals (Sweden)

    Tara Jois

    2017-11-01

    Conclusions: Overall, hepatic ChREBP is protective in regards to hepatic insulin sensitivity and whole body glucose homeostasis. Hepatic ChREBP action can influence other peripheral tissues and is likely essential in coordinating the body's response to different feeding states.

  5. Intermittent Hypoxia Disrupts Glucose Homeostasis in Liver Cells in an Insulin-Dependent and Independent Manner

    Directory of Open Access Journals (Sweden)

    Chen Juan Gu

    2018-05-01

    Full Text Available Background/Aims: Obstructive sleep apnea is associated with diabetes and insulin resistance, but the underlying mechanisms remain unclear. The purpose of the current study was to determine the molecular effects of intermittent hypoxia (IH on hepatic insulin signaling and glucose homeostasis, and whether c-Jun NH2-terminal-kinase (JNK contributed to metabolic responses to IH in liver cells. Methods: The human HepG2 cells and rat FAO cells were exposed to 10, 30, 120, 240 or 360 cycles of IH (1% O2 for 60 s followed by 21% O2 for 60s, 7.5 cycles per hour or normoxia as a control. In a subgroup, we exposed cells to 360 cycles of IH with the JNK inhibitor SP600125. After IH exposure, cell glycogen content and glucose output were measured using colorimetric assay kits. Canonical insulin signaling and gluconeogenic genes were measured by western blot and quantitative polymerase chain reaction. Results: IH decreased insulin-stimulated protein kinase B (AKT/glycogen synthase kinase-3β (GSK-3β phosphorylation in a time-dependent manner, while inhibiting forkhead box protein O1 (FOXO1 expression and phosphoenolpyruvate carboxykinase (PEPCK transcription independent of insulin signaling. JNK inhibitor SP600125 partially restored AKT/ GSK-3β phosphorylation and glycogen synthesis, but did not affect other IH-induced glucose metabolic changes. Conclusion: IH in vitro impaired insulin signal transduction in liver cells as assessed by inhibited AKT/GSK-3β phosphorylation via JNK activation. IH inhibited FOXO1 and gluconeogenesis in an insulin-independent manner.

  6. Dietary Capsaicin Improves Glucose Homeostasis and Alters the Gut Microbiota in Obese Diabetic ob/ob Mice

    Directory of Open Access Journals (Sweden)

    Jun-Xian Song

    2017-08-01

    Full Text Available Background: The effects of capsaicin on obesity and glucose homeostasis are still controversial and the mechanisms underlying these effects remain largely unknown. This study aimed to investigate the potential relationship between the regulation of obesity and glucose homeostasis by dietary capsaicin and the alterations of gut microbiota in obese diabetic ob/ob mice.Methods: The ob/ob mice were subjected to a normal, low-capsaicin (0.01%, or high-capsaicin (0.02% diet for 6 weeks, respectively. Obesity phenotypes, glucose homeostasis, the gut microbiota structure and composition, short-chain fatty acids, gastrointestinal hormones, and pro-inflammatory cytokines were measured.Results: Both the low- and high-capsaicin diets failed to prevent the increase in body weight, adiposity index, and Lee's obesity index. However, dietary capsaicin at both the low and high doses significantly inhibited the increase of fasting blood glucose and insulin levels. These inhibitory effects were comparable between the two groups. Similarly, dietary capsaicin resulted in remarkable improvement in glucose and insulin tolerance. In addition, neither the low- nor high-capsaicin diet could alter the α-diversity and β-diversity of the gut microbiota. Taxonomy-based analysis showed that both the low- and high-capsaicin diets, acting in similar ways, significantly increased the Firmicutes/Bacteroidetes ratio at the phylum level as well as increased the Roseburia abundance and decreased the Bacteroides and Parabacteroides abundances at the genus level. Spearman's correlation analysis revealed that the Roseburia abundance was negatively while the Bacteroides and Parabacteroides abundances were positively correlated to the fasting blood glucose level and area under the curve by the oral glucose tolerance test. Finally, the low- and high-capsaicin diets significantly increased the fecal butyrate and plasma total GLP-1 levels, but decreased plasma total ghrelin, TNF-α, IL-1

  7. Stimulation of the endogenous incretin glucose-dependent insulinotropic peptide by enteral dextrose improves glucose homeostasis and inflammation in murine endotoxemia.

    Science.gov (United States)

    Shah, Faraaz Ali; Singamsetty, Srikanth; Guo, Lanping; Chuan, Byron W; McDonald, Sherie; Cooper, Bryce A; O'Donnell, Brett J; Stefanovski, Darko; Wice, Burton; Zhang, Yingze; O'Donnell, Christopher P; McVerry, Bryan J

    2018-03-01

    Loss of glucose homeostasis during sepsis is associated with increased organ dysfunction and higher mortality. Novel therapeutic strategies to promote euglycemia in sepsis are needed. We have previously shown that early low-level intravenous (IV) dextrose suppresses pancreatic insulin secretion and induces insulin resistance in septic mice, resulting in profound hyperglycemia and worsened systemic inflammation. In this study, we hypothesized that administration of low-level dextrose via the enteral route would stimulate intestinal incretin hormone production, potentiate insulin secretion in a glucose-dependent manner, and thereby improve glycemic control in the acute phase of sepsis. We administered IV or enteral dextrose to 10-week-old male C57BL/6J mice exposed to bacterial endotoxin and measured incretin hormone release, glucose disposal, and proinflammatory cytokine production. Compared with IV administration, enteral dextrose increased circulating levels of the incretin hormone glucose-dependent insulinotropic peptide (GIP) associated with increased insulin release and insulin sensitivity, improved mean arterial pressure, and decreased proinflammatory cytokines in endotoxemic mice. Exogenous GIP rescued glucose metabolism, improved blood pressure, and increased insulin release in endotoxemic mice receiving IV dextrose, whereas pharmacologic inhibition of GIP signaling abrogated the beneficial effects of enteral dextrose. Thus, stimulation of endogenous GIP secretion by early enteral dextrose maintains glucose homeostasis and attenuates the systemic inflammatory response in endotoxemic mice and may provide a therapeutic target for improving glycemic control and clinical outcomes in patients with sepsis. Published by Elsevier Inc.

  8. Neuronal SH2B1 is essential for controlling energy and glucose homeostasis.

    Science.gov (United States)

    Ren, Decheng; Zhou, Yingjiang; Morris, David; Li, Minghua; Li, Zhiqin; Rui, Liangyou

    2007-02-01

    SH2B1 (previously named SH2-B), a cytoplasmic adaptor protein, binds via its Src homology 2 (SH2) domain to a variety of protein tyrosine kinases, including JAK2 and the insulin receptor. SH2B1-deficient mice are obese and diabetic. Here we demonstrated that multiple isoforms of SH2B1 (alpha, beta, gamma, and/or delta) were expressed in numerous tissues, including the brain, hypothalamus, liver, muscle, adipose tissue, heart, and pancreas. Rat SH2B1beta was specifically expressed in neural tissue in SH2B1-transgenic (SH2B1(Tg)) mice. SH2B1(Tg) mice were crossed with SH2B1-knockout (SH2B1(KO)) mice to generate SH2B1(TgKO) mice expressing SH2B1 only in neural tissue but not in other tissues. Systemic deletion of the SH2B1 gene resulted in metabolic disorders in SH2B1(KO) mice, including hyperlipidemia, leptin resistance, hyperphagia, obesity, hyperglycemia, insulin resistance, and glucose intolerance. Neuron-specific restoration of SH2B1beta not only corrected the metabolic disorders in SH2B1(TgKO) mice, but also improved JAK2-mediated leptin signaling and leptin regulation of orexigenic neuropeptide expression in the hypothalamus. Moreover, neuron-specific overexpression of SH2B1 dose-dependently protected against high-fat diet-induced leptin resistance and obesity. These observations suggest that neuronal SH2B1 regulates energy balance, body weight, peripheral insulin sensitivity, and glucose homeostasis at least in part by enhancing hypothalamic leptin sensitivity.

  9. An aqueous extract of Curcuma longa (turmeric) rhizomes stimulates insulin release and mimics insulin action on tissues involved in glucose homeostasis in vitro.

    Science.gov (United States)

    Mohankumar, Sureshkumar; McFarlane, James R

    2011-03-01

    Curcuma longa (turmeric) has been used widely as a spice, particularly in Asian countries. It is also used in the Ayurvedic system of medicine as an antiinflammatory and antimicrobial agent and for numerous other curative properties. The aim of this study was to investigate the effects of an aqueous extract of Curcuma longa (AEC) on tissues involved in glucose homeostasis. The extract was prepared by soaking 100 g of ground turmeric in 1 L of water, which was filtered and stored at -20°C prior to use. Pancreas and muscle tissues of adult mice were cultured in DMEM with 5 or 12 mmol/L glucose and varying doses of extract. The AEC stimulated insulin secretion from mouse pancreatic tissues under both basal and hyperglycaemic conditions, although the maximum effect was only 68% of that of tolbutamide. The AEC induced stepwise stimulation of glucose uptake from abdominal muscle tissues in the presence and absence of insulin, and the combination of AEC and insulin significantly potentiated the glucose uptake into abdominal muscle tissue. However, this effect was attenuated by wortmannin, suggesting that AEC possibly acts via the insulin-mediated glucose uptake pathway. In summary, water soluble compounds of turmeric exhibit insulin releasing and mimicking actions within in vitro tissue culture conditions. Copyright © 2010 John Wiley & Sons, Ltd.

  10. Impact of streptozotocin on altering normal glucose homeostasis during insulin testing in diabetic rats compared to normoglycemic rats

    Directory of Open Access Journals (Sweden)

    Qinna NA

    2015-05-01

    Full Text Available Nidal A Qinna,1 Adnan A Badwan2 1Department of Pharmacology and Biomedical Sciences, Faculty of Pharmacy and Medical Sciences, University of Petra, 2Research and Innovation Centre, The Jordanian Pharmaceutical Manufacturing Co. Plc. (JPM, Amman, Jordan Abstract: Streptozotocin (STZ is currently the most used diabetogenic agent in testing insulin and new antidiabetic drugs in animals. Due to the toxic and disruptive nature of STZ on organs, apart from pancreas, involved in preserving the body’s normal glucose homeostasis, this study aims to reassess the action of STZ in inducing different glucose response states in diabetic rats while testing insulin. Diabetic Sprague-Dawley rats induced with STZ were classified according to their initial blood glucose levels into stages. The effect of randomizing rats in such a manner was investigated for the severity of interrupting normal liver, pancreas, and kidney functions. Pharmacokinetic and pharmacodynamic actions of subcutaneously injected insulin in diabetic and nondiabetic rats were compared. Interruption of glucose homeostasis by STZ was challenged by single and repeated administrations of injected insulin and oral glucose to diabetic rats. In diabetic rats with high glucose (451–750 mg/dL, noticeable changes were seen in the liver and kidney functions compared to rats with lower basal glucose levels. Increased serum levels of recombinant human insulin were clearly indicated by a significant increase in the calculated maximum serum concentration and area under the concentration–time curve. Reversion of serum glucose levels to normal levels pre- and postinsulin and oral glucose administrations to STZ diabetic rats were found to be variable. In conclusion, diabetic animals were more responsive to insulin than nondiabetic animals. STZ was capable of inducing different levels of normal glucose homeostasis disruption in rats. Both pharmacokinetic and pharmacodynamic actions of insulin were

  11. Smurf1 Inhibits Osteoblast Differentiation, Bone Formation, and Glucose Homeostasis through Serine 148

    Directory of Open Access Journals (Sweden)

    Junko Shimazu

    2016-04-01

    Full Text Available The E3 ubiquitin ligase Smurf1 targets the master regulator of osteoblast differentiation, Runx2, for degradation, yet the function of Smurf1, if any, during osteoblast differentiation in vivo is ill defined. Here, we show that Smurf1 prevents osteoblast differentiation by decreasing Runx2 accumulation in osteoblasts. Remarkably, mice harboring a substitution mutation at serine 148 (S148 in Smurf1 that prevents its phosphorylation by AMPK (Smurf1ki/ki display a premature osteoblast differentiation phenotype that is equally severe as that of Smurf1−/− mice, as well as a high bone mass, and are also hyperinsulinemic and hypoglycemic. Consistent with the fact that Smurf1 targets the insulin receptor for degradation, there is, in Smurf1ki/ki mice, an increase in insulin signaling in osteoblasts that triggers a rise in the circulating levels of osteocalcin, a hormone that favors insulin secretion. These results identify Smurf1 as a determinant of osteoblast differentiation during the development of bone formation and glucose homeostasis post-natally and demonstrate the necessity of S148 for these functions.

  12. Activating transcription factor 3 is a target molecule linking hepatic steatosis to impaired glucose homeostasis.

    Science.gov (United States)

    Kim, Ji Yeon; Park, Keon Jae; Hwang, Joo-Yeon; Kim, Gyu Hee; Lee, DaeYeon; Lee, Yoo Jeong; Song, Eun Hyun; Yoo, Min-Gyu; Kim, Bong-Jo; Suh, Young Ho; Roh, Gu Seob; Gao, Bin; Kim, Won; Kim, Won-Ho

    2017-08-01

    predicting the progression of NAFLD and the development of T2D. Furthermore, given the significant association between hepatic ATF3 expression and both hepatic steatosis and impaired glucose homeostasis, in vivo ATF3 silencing may be a potential central strategy for preventing and managing NAFLD and T2D. Copyright © 2017 European Association for the Study of the Liver. All rights reserved.

  13. Leptin and insulin pathways in POMC and AgRP neurons that modulate energy balance and glucose homeostasis

    Science.gov (United States)

    Varela, Luis; Horvath, Tamas L

    2012-01-01

    With the steady rise in the prevalence of obesity and its associated diseases, research aimed at understanding the mechanisms that regulate and control whole body energy homeostasis has gained new interest. Leptin and insulin, two anorectic hormones, have key roles in the regulation of body weight and energy homeostasis, as highlighted by the fact that several obese patients develop resistance to these hormones. Within the brain, the hypothalamic proopiomelanocortin and agouti-related protein neurons have been identified as major targets of leptin and insulin action. Many studies have attempted to discern the individual contributions of various components of the principal pathways that mediate the central effects of leptin and insulin. The aim of this review is to discuss the latest findings that might shed light on, and lead to a better understanding of, energy balance and glucose homeostasis. In addition, recently discovered targets and mechanisms that mediate hormonal action in the brain are highlighted. PMID:23146889

  14. Effect of Ethanolic Extract of Emblica officinalis (Amla on Glucose Homeostasis in Rats Fed with High Fat Diet

    Directory of Open Access Journals (Sweden)

    Pallavi S. Kanthe

    2017-07-01

    Full Text Available Background: Emblica officinalis contains many biological active components which are found to have some medicinal properties against diseases. Aim and Objectives: To assess hypolipidemic and glucose regulatory actions of Ethanolic Extract of Emblica officinalis (EEO on High Fat Diet (HFD fed experimental rats. Material and Methods: Twenty four rats were divided into four groups, having six rats in each group as following; Group I- Control (20% fat; Group II (EEO 100 mg/kg/b w; Group III (30% fat and Group IV (30% fat + EEO 100 mg/kg/b w. The treatment was continued for 21 days. Gravimetric parameters and lipid profiles of all the groups were measured. Oral Glucose Tolerance Test (OGTT, fasting and postprandial glucose and fasting insulin levels were estimated. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR was calculated. Statistical analysis was done. Results: Significant alteration in serum lipid profile, fasting and post prandial blood glucose levels and fasting insulin level were observed in rats of Group III fed with high fat diet. Supplementation of EEO improved both of glycemic and lipid profiles in rats of Group IV fed with high fat diet. Conclusion: Results from the study indicate the beneficial role of EEO on dyslipidemia and glucose homeostasis in rats treated with high fat diet.

  15. Inositol 1,4,5-trisphosphate receptor 1 mutation perturbs glucose homeostasis and enhances susceptibility to diet-induced diabetes.

    Science.gov (United States)

    Ye, Risheng; Ni, Min; Wang, Miao; Luo, Shengzhan; Zhu, Genyuan; Chow, Robert H; Lee, Amy S

    2011-08-01

    The inositol 1,4,5-trisphosphate receptors (IP3Rs) as ligand-gated Ca(2)(+) channels are key modulators of cellular processes. Despite advances in understanding their critical role in regulating neuronal function and cell death, how this family of proteins impact cell metabolism is just emerging. Unexpectedly, a transgenic mouse line (D2D) exhibited progressive glucose intolerance as a result of transgene insertion. Inverse PCR was used to identify the gene disruption in the D2D mice. This led to the discovery that Itpr1 is among the ten loci disrupted in chromosome 6. Itpr1 encodes for IP3R1, the most abundant IP3R isoform in mouse brain and also highly expressed in pancreatic β-cells. To study IP3R1 function in glucose metabolism, we used the Itpr1 heterozygous mutant mice, opt/+. Glucose homeostasis in male mice cohorts was examined by multiple approaches of metabolic phenotyping. Under regular diet, the opt/+ mice developed glucose intolerance but no insulin resistance. Decrease in second-phase glucose-stimulated blood insulin level was observed in opt/+ mice, accompanied by reduced β-cell mass and insulin content. Strikingly, when fed with high-fat diet, the opt/+ mice were more susceptible to the development of hyperglycemia, glucose intolerance, and insulin resistance. Collectively, our studies identify the gene Itpr1 being interrupted in the D2D mice and uncover a novel role of IP3R1 in regulation of in vivo glucose homeostasis and development of diet-induced diabetes.

  16. Diagnostic Accuracies of Glycated Hemoglobin, Fructosamine, and Homeostasis Model Assessment of Insulin Resistance in Predicting Impaired Fasting Glucose, Impaired Glucose Tolerance, or New Onset Diabetes After Transplantation.

    Science.gov (United States)

    Rosettenstein, Kerri; Viecelli, Andrea; Yong, Kenneth; Nguyen, Hung Do; Chakera, Aron; Chan, Doris; Dogra, Gursharan; Lim, Ee Mun; Wong, Germaine; Lim, Wai H

    2016-07-01

    New onset diabetes after transplantation (NODAT) is associated with a 3-fold greater risk of cardiovascular disease events, with early identification and treatment potentially attenuating this risk. The optimal screening test to identify those with NODAT remains unclear, and the aim of this study was to examine the diagnostic accuracies of 4 screening tests in identifying impaired fasting glucose, impaired glucose tolerance (IGT), and NODAT. This is a single-center prospective cohort study of 83 nondiabetic kidney transplant recipients between 2008 and 2011. Oral glucose tolerance test was considered the gold standard in identifying IFG/IGT or NODAT. Diagnostic accuracies of random blood glucose, glycated hemoglobin (HBA1c), fructosamine, and Homeostasis Model Assessment-Insulin Resistance in predicting IFG/IGT or NODAT were assessed using the area under the receiver operating characteristic curve. Forty (48%) recipients had IFG/IGT or NODAT. Compared with HBA1c with adjusted area under the curve (AUC) of 0.88 (95% confidence interval [95% CI], 0.77-0.93), fructosamine was the most accurate test with adjusted AUC of 0.92 (95% CI, 0.83-0.96). The adjusted AUCs of random blood glucose and Homeostasis Model Assessment-Insulin Resistance in identifying IFG/IGT were between 0.81 and 0.85. Restricting to identifying IGT/NODAT using 2-hour oral glucose tolerance test (n = 66), fructosamine was the most accurate diagnostic test with adjusted AUC of 0.93 (95% CI, 0.84-0.99), but not statistically different to HBA1c with adjusted AUC of 0.88 (95% CI, 0.76-0.96). Although HBA1c is an acceptable and widely used screening test in detecting IFG/IGT or NODAT, fructosamine may be a more accurate diagnostic test but this needs to be further examined in larger cohorts.

  17. Lipoprotein lipase in hypothalamus is a key regulator of body weight gain and glucose homeostasis in mice.

    Science.gov (United States)

    Laperrousaz, Elise; Moullé, Valentine S; Denis, Raphaël G; Kassis, Nadim; Berland, Chloé; Colsch, Benoit; Fioramonti, Xavier; Philippe, Erwann; Lacombe, Amélie; Vanacker, Charlotte; Butin, Noémie; Bruce, Kimberley D; Wang, Hong; Wang, Yongping; Gao, Yuanqing; Garcia-Caceres, Cristina; Prévot, Vincent; Tschöp, Matthias H; Eckel, Robert H; Le Stunff, Hervé; Luquet, Serge; Magnan, Christophe; Cruciani-Guglielmacci, Céline

    2017-07-01

    Regulation of energy balance involves the participation of many factors, including nutrients, among which are circulating lipids, acting as peripheral signals informing the central nervous system of the energy status of the organism. It has been shown that neuronal lipoprotein lipase (LPL) participates in the control of energy balance by hydrolysing lipid particles enriched in triacylglycerols. Here, we tested the hypothesis that LPL in the mediobasal hypothalamus (MBH), a well-known nucleus implicated in the regulation of metabolic homeostasis, could also contribute to the regulation of body weight and glucose homeostasis. We injected an adeno-associated virus (AAV) expressing Cre-green fluorescent protein into the MBH of Lpl-floxed mice (and wild-type mice) to specifically decrease LPL activity in the MBH. In parallel, we injected an AAV overexpressing Lpl into the MBH of wild-type mice. We then studied energy homeostasis and hypothalamic ceramide content. The partial deletion of Lpl in the MBH in mice led to an increase in body weight compared with controls (37.72 ± 0.7 g vs 28.46 ± 0.12, p < 0.001) associated with a decrease in locomotor activity. These mice developed hyperinsulinaemia and glucose intolerance. This phenotype also displayed reduced expression of Cers1 in the hypothalamus as well as decreased concentration of several C18 species of ceramides and a 3-fold decrease in total ceramide intensity. Conversely, overexpression of Lpl specifically in the MBH induced a decrease in body weight. Our study shows that LPL in the MBH is an important regulator of body weight and glucose homeostasis.

  18. Glucose 6 phosphate dehydrogenase deficiency in adults

    International Nuclear Information System (INIS)

    Khan, M.

    2004-01-01

    Objective: To determine the frequency of glucose-6-phosphate dehydrogenase (G6PD) deficiency in adults presented with anemia. Subjects and Methods: Eighteen months admission data was reviewed for G6PD deficiency as a cause of anemia. Anemia was defined by world health organization (WHO) criteria as haemoglobin less than 11.3 gm%. G6PD activity was measured by Sigma dye decolorisation method. All patients were screened for complications of hemolysis and its possible cause. Patients with more than 13 years of age were included in the study. Results: Out of 3600 patients admitted, 1440 were found anaemic and 49 as G6PD deficient. So the frequency of G6PD deficiency in anaemic patients was 3.4% and the overall frequency is 1.36%. G6PD deficiency among males and females was three and six percent respectively. Antimalarials and antibiotics containing sulphonamide group were the most common precipitating factors for hemolysis. Anemia and jaundice were the most common presentations while malaria was the most common associated disease. Acute renal failure was the most severe complication occurring in five patients with two deaths. Conclusion: G6PD deficiency is a fairly common cause of anemia with medicine as common precipitating factor for hemolysis. Such complications can be avoided with early recognition of the disease and avoiding indiscriminate use of medicine. (author)

  19. CISH has no non-redundant functions in glucose homeostasis or beta cell proliferation during pregnancy in mice.

    Science.gov (United States)

    Jiao, Yang; Rieck, Sebastian; Le Lay, John; Kaestner, Klaus H

    2013-11-01

    Increased beta cell proliferation during pregnancy is mediated by the Janus kinase 2/signal transducer and activator of transcription 5 (JAK2/STAT5) signalling pathway in response to increased lactogen levels. Activation of the pathway leads to transcriptional upregulation of Cish (encoding cytokine-inducible SH2 domain-containing protein), a member of the suppressor of cytokine signalling (SOCS) family of genes, forming a negative-feedback loop. Here, we examined whether conditional gene ablation of Cish in the pancreas improves beta cell proliferation and beta cell function during pregnancy in mice. We derived mice with a novel, conditional loxP allele for Cish. Pancreas-specific ablation of Cish was achieved by crossing Cish (loxP/loxP) mice with Pdx1-Cre (Early) mice. Beta cell proliferation was quantified by BrdU labelling. Glucose homeostasis was examined with glucose tolerance tests and determination of plasma insulin levels. The expression of other Socs genes and target genes of p-STAT5 related to beta cell function and beta cell proliferation was determined by quantitative PCR. There was no difference in beta cell proliferation or glucose homeostasis between the Cish mutant group and the control group. The p-STAT5 protein level was the same in Cish mutant and control mice. Socs2 gene expression was higher in Cish mutant than control mice at pregnancy day 9.5. The expression of other Socs genes was the same between control and mutant mice. Our results show that CISH has no non-redundant functions in beta cell proliferation or glucose homeostasis during pregnancy in mice. Socs2 might compensate for the loss of Cish during pregnancy.

  20. AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons.

    Science.gov (United States)

    Claret, Marc; Smith, Mark A; Batterham, Rachel L; Selman, Colin; Choudhury, Agharul I; Fryer, Lee G D; Clements, Melanie; Al-Qassab, Hind; Heffron, Helen; Xu, Allison W; Speakman, John R; Barsh, Gregory S; Viollet, Benoit; Vaulont, Sophie; Ashford, Michael L J; Carling, David; Withers, Dominic J

    2007-08-01

    Hypothalamic AMP-activated protein kinase (AMPK) has been suggested to act as a key sensing mechanism, responding to hormones and nutrients in the regulation of energy homeostasis. However, the precise neuronal populations and cellular mechanisms involved are unclear. The effects of long-term manipulation of hypothalamic AMPK on energy balance are also unknown. To directly address such issues, we generated POMC alpha 2KO and AgRP alpha 2KO mice lacking AMPK alpha2 in proopiomelanocortin- (POMC-) and agouti-related protein-expressing (AgRP-expressing) neurons, key regulators of energy homeostasis. POMC alpha 2KO mice developed obesity due to reduced energy expenditure and dysregulated food intake but remained sensitive to leptin. In contrast, AgRP alpha 2KO mice developed an age-dependent lean phenotype with increased sensitivity to a melanocortin agonist. Electrophysiological studies in AMPK alpha2-deficient POMC or AgRP neurons revealed normal leptin or insulin action but absent responses to alterations in extracellular glucose levels, showing that glucose-sensing signaling mechanisms in these neurons are distinct from those pathways utilized by leptin or insulin. Taken together with the divergent phenotypes of POMC alpha 2KO and AgRP alpha 2KO mice, our findings suggest that while AMPK plays a key role in hypothalamic function, it does not act as a general sensor and integrator of energy homeostasis in the mediobasal hypothalamus.

  1. Maintenance of Glucose Homeostasis through Acetylation of the Metabolic Transcriptional Coactivator PGC-1alpha

    National Research Council Canada - National Science Library

    Puigserver, Pere

    2007-01-01

    ... hepatic glucose production. This investigation has a define scope to specifically test how these proteins control the acetylation status of PGC-1alpha and what is the functional effect in blood glucose levels...

  2. Gliadin affects glucose homeostasis and intestinal metagenome in C57BL6 mice fed a high-fat diet

    DEFF Research Database (Denmark)

    Zhang, Li; Hansen, Axel Kornerup; Bahl, Martin Iain

    limited. The aim of this study was to investigate the effect of gliadin on glucose homeostasis and intestinal ecology in the mouse. Forty male C57BL/6 mice were fed a high-fat diet containing either 4% gliadin or no gliadin for 22 weeks. Gliadin consumption significantly increased the HbA1c level over......Dietary gluten and its component gliadin are well-known environmental triggers of celiac disease and important actors in type-1 diabetes, and are reported to induce alterations in the intestinal microbiota. However, research on the impact of gluten on type-2 diabetes in non-celiac subjects is more...... time, with a borderline significance of higher HOMA-IR (homeostasis model assessment of insulin resistance) after 22 weeks. Sequencing of the V3 region of the bacterial 16S rRNA genes showed that gliadin altered the abundance of 81 bacterial taxa, separating the intestinal microbial profile...

  3. The Essential Role of Mbd5 in the Regulation of Somatic Growth and Glucose Homeostasis in Mice

    Science.gov (United States)

    Du, Yarui; Liu, Bo; Guo, Fan; Xu, Guifang; Ding, Yuqiang; Liu, Yong; Sun, Xin; Xu, Guoliang

    2012-01-01

    Methyl-CpG binding domain protein 5 (MBD5) belongs to the MBD family proteins, which play central roles in transcriptional regulation and development. The significance of MBD5 function is highlighted by recent studies implicating it as a candidate gene involved in human 2q23.1 microdeletion syndrome. To investigate the physiological role of Mbd5, we generated knockout mice. The Mbd5-deficient mice showed growth retardation, wasting and pre-weaning lethality. The observed growth retardation was associated with the impairment of GH/IGF-1 axis in Mbd5-null pups. Conditional knockout of Mbd5 in the brain resulted in the similar phenotypes as whole body deletion, indicating that Mbd5 functions in the nervous system to regulate postnatal growth. Moreover, the mutant mice also displayed enhanced glucose tolerance and elevated insulin sensitivity as a result of increased insulin signaling, ultimately resulting in disturbed glucose homeostasis and hypoglycemia. These results indicate Mbd5 as an essential factor for mouse postnatal growth and maintenance of glucose homeostasis. PMID:23077600

  4. Effects of dietary beef tallow and soy oil on glucose and cholesterol homeostasis in normal and diabetic pigs

    International Nuclear Information System (INIS)

    Woollett, L.A.

    1987-01-01

    Toe valuate whether dietary fats of different degrees of unsaturation alter glucose and very low density lipoprotein-cholesterol (VLDL-CH) homeostasis, normal and alloxan-diabetic pigs were fed diets containing either beef tallow or soy oil as the primary source of fat for 6 weeks. After intra-arterial and oral doses of glucose, pigs fed soy oil had similar glucose and greater insulin concentrations in plasma when compared with pigs fed beef tallow. Beef tallow-fed pigs additionally were 40% more glucose effective than were soy oil-fed pigs. Disappearance of injected autologous 14 C-VLDL-CH was analyzed in pigs using a two-pool model. Diabetes resulted in a twofold increase in half-lives and a 60-fold increase in pool sizes of the primary and secondary components of VLDL-CH disappearance when compared with those of normal pigs. In normal pigs, feeding beef tallow resulted in longer half-lives of both components of VLDL-CH disappearance and no effect in pool size of both components of VLDL-CH disappearance than did feeding soy oil. In comparison, diabetic pigs fed beef tallow had a similar half-life of the primary component, a twofold shorter half-life of the secondary component, and threefold larger pool size of the primary component, and a similar pool size of the secondary component of VLDL-CH disappearance than did diabetic pigs fed soy oil. Thus, dietary fat seems to play an important role in regulation of glucose and VLDL-CH homeostasis in normal and diabetic animals

  5. Genetic models rule out a major role of beta cell glycogen in the control of glucose homeostasis.

    Science.gov (United States)

    Mir-Coll, Joan; Duran, Jordi; Slebe, Felipe; García-Rocha, Mar; Gomis, Ramon; Gasa, Rosa; Guinovart, Joan J

    2016-05-01

    Glycogen accumulation occurs in beta cells of diabetic patients and has been proposed to partly mediate glucotoxicity-induced beta cell dysfunction. However, the role of glycogen metabolism in beta cell function and its contribution to diabetes pathophysiology remain poorly understood. We investigated the function of beta cell glycogen by studying glucose homeostasis in mice with (1) defective glycogen synthesis in the pancreas; and (2) excessive glycogen accumulation in beta cells. Conditional deletion of the Gys1 gene and overexpression of protein targeting to glycogen (PTG) was accomplished by Cre-lox recombination using pancreas-specific Cre lines. Glucose homeostasis was assessed by determining fasting glycaemia, insulinaemia and glucose tolerance. Beta cell mass was determined by morphometry. Glycogen was detected histologically by periodic acid-Schiff's reagent staining. Isolated islets were used for the determination of glycogen and insulin content, insulin secretion, immunoblots and gene expression assays. Gys1 knockout (Gys1 (KO)) mice did not exhibit differences in glucose tolerance or basal glycaemia and insulinaemia relative to controls. Insulin secretion and gene expression in isolated islets was also indistinguishable between Gys1 (KO) and controls. Conversely, despite effective glycogen overaccumulation in islets, mice with PTG overexpression (PTG(OE)) presented similar glucose tolerance to controls. However, under fasting conditions they exhibited lower glycaemia and higher insulinaemia. Importantly, neither young nor aged PTG(OE) mice showed differences in beta cell mass relative to age-matched controls. Finally, a high-fat diet did not reveal a beta cell-autonomous phenotype in either model. Glycogen metabolism is not required for the maintenance of beta cell function. Glycogen accumulation in beta cells alone is not sufficient to trigger the dysfunction or loss of these cells, or progression to diabetes.

  6. Adult glucose metabolism in extremely birthweight-discordant monozygotic twins

    DEFF Research Database (Denmark)

    Frost, M; Petersen, I; Brixen, K

    2012-01-01

    Low birthweight (BW) is associated with increased risk of type 2 diabetes. We compared glucose metabolism in adult BW-discordant monozygotic (MZ) twins, thereby controlling for genetic factors and rearing environment....

  7. The Action of Antidiabetic Plants of the Canadian James Bay Cree Traditional Pharmacopeia on Key Enzymes of Hepatic Glucose Homeostasis

    Directory of Open Access Journals (Sweden)

    Abir Nachar

    2013-01-01

    Full Text Available We determined the capacity of putative antidiabetic plants used by the Eastern James Bay Cree (Canada to modulate key enzymes of gluconeogenesis and glycogen synthesis and key regulating kinases. Glucose-6-phosphatase (G6Pase and glycogen synthase (GS activities were assessed in cultured hepatocytes treated with crude extracts of seventeen plant species. Phosphorylation of AMP-dependent protein kinase (AMPK, Akt, and Glycogen synthase kinase-3 (GSK-3 were probed by Western blot. Seven of the seventeen plant extracts significantly decreased G6Pase activity, Abies balsamea and Picea glauca, exerting an effect similar to insulin. This action involved both Akt and AMPK phosphorylation. On the other hand, several plant extracts activated GS, Larix laricina and A. balsamea, far exceeding the action of insulin. We also found a significant correlation between GS stimulation and GSK-3 phosphorylation induced by plant extract treatments. In summary, three Cree plants stand out for marked effects on hepatic glucose homeostasis. P. glauca affects glucose production whereas L. laricina rather acts on glucose storage. However, A. balsamea has the most promising profile, simultaneously and powerfully reducing G6Pase and stimulating GS. Our studies thus confirm that the reduction of hepatic glucose production likely contributes to the therapeutic potential of several antidiabetic Cree traditional medicines.

  8. Cucurbitane Triterpenoids from the Fruits of Momordica Charantia Improve Insulin Sensitivity and Glucose Homeostasis in Streptozotocin-Induced Diabetic Mice.

    Science.gov (United States)

    Han, Joo-Hui; Tuan, Nguyen Quoc; Park, Min-Ho; Quan, Khong Trong; Oh, Joonseok; Heo, Kyung-Sun; Na, MinKyun; Myung, Chang-Seon

    2018-04-01

    Momordica charantia (M. charantia) has antidiabetic effects, and cucurbitane-type triterpenoid is one of the compounds of M. charantia. This study aims to investigate whether the new cucurbitane-type triterpenoids affect insulin sensitivity both in vitro and in vivo, and the underlying mechanisms. Four compounds (C1-C4) isolated from the ethanol extract of M. charantia enhance glucose uptake in C2C12 myotubes via insulin receptor substrate-1 (IRS-1) rather than via adenosine monophosphate-activated protein kinase. The most potent, compound 2 (C2), significantly increases the activation of IRS-1 and downstream signaling pathways, resulting in glucose transporter 4 translocation. Furthermore, these C2-induced in vitro effects are blocked by specific signal inhibitors. We further evaluate the antidiabetic effect of C2 using a streptozotocin (STZ)-induced diabetic mouse model. Consistent with in vitro data, treatment with C2 (1.68 mg kg -1 ) significantly decreases blood glucose level and enhances glycogen storage in STZ-injected mice. These effects appear to be mediated by the IRS-1 signaling pathway in skeletal muscle, not in adipose and liver tissues, suggesting that C2 improves hyperglycemia by increasing glucose uptake into skeletal muscle. Our findings demonstrate that the new cucurbitane-type triterpenoids have potential for prevention and management of diabetes by improving insulin sensitivity and glucose homeostasis. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. [Glucose-monitoring neurons of the medial ventrolateral prefrontal (orbitofrontal) cortex are involved in the maintenance of homeostasis].

    Science.gov (United States)

    Szabó, István; Hormay, Edina; Csetényi, Bettina; Nagy, Bernadett; Karádi, Zoltán

    2017-05-01

    The medial orbitofrontal cortex is involved in the regulation of feeding and metabolism. Little is known, however, about the role of local glucose-monitoring neurons in these processes, and our knowledge is also poor about characteristics of these cells. The functional significance of these chemosensory neurons was to be elucidated. Electrophysiology, by the multibarreled microelectrophoretic technique, and metabolic investigations, after streptozotocin induced selective destruction of the chemosensory neurons, were employed. Fifteen percent of the neurons responded to glucose, and these chemosensory cells displayed differential neurotransmitter and taste sensitivities. In acute glucose tolerance test, at the 30th and 60th minutes, blood glucose level in the streptozotocin-treated rats was significantly higher than that in the controls. The plasma triglyceride concentrations were also higher in the streptozotocin-treated group. Glucose-monitoring neurons of the medial orbitofrontal cortex integrate internal and external environmental signals, and monitor metabolic processes, thus, are indispensable to maintain the healthy homeostasis. Orv Hetil. 2017; 158(18): 692-700.

  10. Human monoclonal antibodies against glucagon receptor improve glucose homeostasis by suppression of hepatic glucose output in diet-induced obese mice.

    Directory of Open Access Journals (Sweden)

    Wook-Dong Kim

    Full Text Available AIM: Glucagon is an essential regulator of hepatic glucose production (HGP, which provides an alternative therapeutic target for managing type 2 diabetes with glucagon antagonists. We studied the effect of a novel human monoclonal antibody against glucagon receptor (GCGR, NPB112, on glucose homeostasis in diet-induced obese (DIO mice. METHODS: The glucose-lowering efficacy and safety of NPB112 were investigated in DIO mice with human GCGR for 11 weeks, and a hyperinsulinemic-euglycemic clamp study was conducted to measure HGP. RESULTS: Single intraperitoneal injection of NPB112 with 5 mg/kg effectively decreased blood glucose levels in DIO mice for 5 days. A significant reduction in blood glucose was observed in DIO mice treated with NPB112 at a dose ≥5 mg/kg for 6 weeks, and its glucose-lowering effect was dose-dependent. Long-term administration of NPB112 also caused a mild 29% elevation in glucagon level, which was returned to the normal range after discontinuation of treatment. The clamp study showed that DIO mice injected with NPB112 at 5 mg/kg were more insulin sensitive than control mice, indicating amelioration of insulin resistance by treatment with NPB112. DIO mice treated with NPB112 showed a significant improvement in the ability of insulin to suppress HGP, showing a 33% suppression (from 8.3 mg/kg/min to 5.6 mg/kg/min compared to the 2% suppression (from 9.8 mg/kg/min to 9.6 mg/kg/min in control mice. In addition, no hypoglycemia or adverse effect was observed during the treatment. CONCLUSIONS: A novel human monoclonal GCGR antibody, NPB112, effectively lowered the glucose level in diabetic animal models with mild and reversible hyperglucagonemia. Suppression of excess HGP with NPB112 may be a promising therapeutic modality for the treatment of type 2 diabetes.

  11. Vitamin D and prebiotics may benefit the intestinal microbacteria and improve glucose homeostasis in prediabetes and type 2 diabetes.

    Science.gov (United States)

    Barengolts, Elena

    2013-01-01

    To review the role of human large bowel microbacteria (microbiota) in the glucose homeostasis, to address vitamin D (VD) and prebiotics interactions with microbiota, and to summarize recent randomized clinical trials (RCTs) of VD and prebiotics supplementation in prediabetes (PreDM) and type 2 diabetes mellitus (T2DM). Primary literature was reviewed in the following areas: composition and activity of human microbiota associated with PreDM and T2DM, interactions between microbiota and glucose homeostasis, the interaction of microbiota with VD/prebiotics, and RCTs of VD/prebiotics in subjects with PreDM or T2DM. The human microbiota is comprised of 100 trillion bacteria with an aggregate genome that is 150-fold larger than the human genome. Data from the animal models and human studies reveal that an "obesogenic" diet results into the initial event of microbiota transformation from symbiosis to dysbiosis. The microbial antigens, such as Gram(-) bacteria and lipopolysaccharide (LPS), translocate to the host interior and trigger increased energy harvesting and Toll-like receptor (TLR) activation with subsequent inflammatory pathways signaling. The "double hit" of steatosis (ectopic fat accumulation) and "-itis" (inflammation) and contribution of "corisks" (e.g., vitamin D deficiency [VDD]) are required to activate molecular signaling, including impaired insulin signaling and secretion, that ends with T2DM and associated diseases. Dietary changes (e.g., prebiotics, VD supplementation) may ameliorate this process if initiated prior to the process becoming irreversible. Emerging evidence suggests an important role of microbiota in glucose homeostasis. VD supplementation and prebiotics may be useful in managing PreDM and T2DM.

  12. Lifestyle, glucose regulation and the cognitive effects of glucose load in middle-aged adults.

    Science.gov (United States)

    Riby, Leigh M; McLaughlin, Jennifer; Riby, Deborah M; Graham, Cheryl

    2008-11-01

    Interventions aimed at improving glucose regulatory mechanisms have been suggested as a possible source of cognitive enhancement in the elderly. In particular, previous research has identified episodic memory as a target for facilitation after either moderate increases in glycaemia (after a glucose drink) or after improvements in glucose regulation. The present study aimed to extend this research by examining the joint effects of glucose ingestion and glucose regulation on cognition. In addition, risk factors associated with the development of poor glucose regulation in middle-aged adults were considered. In a repeated measures design, thirty-three middle-aged adults (aged 35-55 years) performed a battery of memory and non-memory tasks after either 25 g or 50 g glucose or a sweetness matched placebo drink. To assess the impact of individual differences in glucose regulation, blood glucose measurements were taken on four occasions during testing. A lifestyle and diet questionnaire was also administered. Consistent with previous research, episodic memory ability benefited from glucose ingestion when task demands were high. Blood glucose concentration was also found to predict performance across a number of cognitive domains. Interestingly, the risk factors associated with poor glucose regulation were linked to dietary impacts traditionally associated with poor health, e.g. the consumption of high-sugar sweets and drinks. The research replicates earlier work suggesting that task demands are critical to the glucose facilitation effect. Importantly, the data demonstrate clear associations between elevated glycaemia and relatively poor cognitive performance, which may be partly due to the effect of dietary and lifestyle factors.

  13. Catalpic acid decreases abdominal fat deposition, improves glucose homeostasis and upregulates PPAR alpha expression in adipose tissue.

    Science.gov (United States)

    Hontecillas, Raquel; Diguardo, Maggie; Duran, Elisa; Orpi, Marcel; Bassaganya-Riera, Josep

    2008-10-01

    Catalpic acid (CAT) is a conjugated linolenic acid (CLN) isomer containing trans-9, trans-11, cis-13 double bonds in an 18-carbon chain and it is found primarily in the seed oil of ornamental and medicinal trees and shrubs of the family Bignoniaceae. The objective of this study was to investigate whether CAT decreases obesity and ameliorates insulin sensitivity and glucose tolerance in mice fed high-fat diets. To test the efficacy of CAT in decreasing obesity and diabetes we used both a model of diet-induced obesity (DIO) and a genetic model of obesity (i.e., mice lacking the leptin receptor). Blood was collected on days 0, 7, 14, 21 and 28 for determining fasting glucose and insulin concentrations in plasma. In addition, a glucose tolerance test was administered on day 28. We found that dietary CAT (1g/100g) decreased fasting plasma glucose and insulin concentrations, ameliorated the glucose normalizing ability following glucose challenge and decreased abdominal white adipose tissue accumulation. In white adipose tissue (WAT), CAT upregulated peroxisome proliferator-activated receptor (PPAR) alpha and its responsive genes [i.e., stearoyl-coenzyme A desaturase (SCD1) and enoyl-coenzyme A hydratase (ECH)], increased concentrations of high-density lipoprotein (HDL) cholesterol and decreased plasma triglyceride (TG) levels. CAT decreased abdominal fat deposition, increased HDL cholesterol, decreased TG concentrations, decreased glucose and insulin homeostasis and modulated WAT gene expression in a manner reminiscent of the actions of the PPAR alpha-activating fibrate class of lipid-lowering drugs.

  14. The ICET-A Recommendations for the Diagnosis and Management of Disturbances of Glucose Homeostasis in Thalassemia Major Patients

    Science.gov (United States)

    De Sanctis, Vincenzo; Soliman, Ashraf T.; Elsedfy, Heba; Yaarubi, Saif AL; Skordis, Nicos; Khater, Doaa; El Kholy, Mohamed; Stoeva, Iva; Fiscina, Bernadette; Angastiniotis, Michael; Daar, Shahina; Kattamis, Christos

    2016-01-01

    Iron overload in patients with thalassemia major (TM) affects glucose regulation and is mediated by several mechanisms. The pathogenesis of glycaemic abnormalities in TM is complex and multifactorial. It has been predominantly attributed to a combination of reduced insulin secretory capacity and insulin resistance. The exact mechanisms responsible for progression from norm glycaemia to overt diabetes in these patients are still poorly understood but are attributed mainly to insulin deficiency resulting from the toxic effects of iron deposited in the pancreas and insulin resistance. A group of endocrinologists, haematologists and paediatricians, members of the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescence Medicine (ICET-A) convened to formulate recommendations for the diagnosis and management of abnormalities of glucose homeostasis in thalassemia major patients on the basis of available evidence from clinical and laboratory data and consensus practice. The results of their work and discussions are described in this article. PMID:27872738

  15. 31P NMR studies of pH homeostasis in intact adult Fasciola hepatica

    NARCIS (Netherlands)

    Tielens, A.G.M.; Nicolaij, K.; Bergh, van S.G.

    1982-01-01

    31P NMR was used to measure the intracellular pH in live adult Fasciola hepatica. The results demonstrate that at external pH values above 7.0, pH homeostasis keeps the intracellular pH at 7.0. At external pH values below 7.0 the intracellular pH is less strictly regulated.

  16. Heads and tails of endoderm development and adult tissue homeostasis in zebrafish

    NARCIS (Netherlands)

    Faro, A.

    2010-01-01

    The regulatory signaling pathways crucial during embryonic development seem to play key roles in adult tissues homeostasis and are often deregulated in pathological conditions. The Wnt pathway plays a pivotal role in orchestrating cell fate decisions during embryonic development, organogenesis, and

  17. Thyroid hormone regulation of adult intestinal stem cells: Implications on intestinal development and homeostasis.

    Science.gov (United States)

    Sun, Guihong; Roediger, Julia; Shi, Yun-Bo

    2016-12-01

    Organ-specific adult stem cells are essential for organ homeostasis, tissue repair and regeneration. The formation of such stem cells often takes place during postembryonic development, a period around birth in mammals when plasma thyroid hormone concentration is high. The life-long self-renewal of the intestinal epithelium has made mammalian intestine a valuable model to study the function and regulation and adult stem cells. On the other hand, much less is known about how the adult intestinal stem cells are formed during vertebrate development. Here, we will review some recent progresses on this subject, focusing mainly on the formation of the adult intestine during Xenopus metamorphosis. We will discuss the role of thyroid hormone signaling pathway in the process and potential molecular conservations between amphibians and mammals as well as the implications in organ homeostasis and human diseases.

  18. Oxygen Glucose Deprivation in Rat Hippocampal Slice Cultures Results in Alterations in Carnitine Homeostasis and Mitochondrial Dysfunction

    Science.gov (United States)

    Rau, Thomas F.; Lu, Qing; Sharma, Shruti; Sun, Xutong; Leary, Gregory; Beckman, Matthew L.; Hou, Yali; Wainwright, Mark S.; Kavanaugh, Michael; Poulsen, David J.; Black, Stephen M.

    2012-01-01

    Mitochondrial dysfunction characterized by depolarization of mitochondrial membranes and the initiation of mitochondrial-mediated apoptosis are pathological responses to hypoxia-ischemia (HI) in the neonatal brain. Carnitine metabolism directly supports mitochondrial metabolism by shuttling long chain fatty acids across the inner mitochondrial membrane for beta-oxidation. Our previous studies have shown that HI disrupts carnitine homeostasis in neonatal rats and that L-carnitine can be neuroprotective. Thus, this study was undertaken to elucidate the molecular mechanisms by which HI alters carnitine metabolism and to begin to elucidate the mechanism underlying the neuroprotective effect of L-carnitine (LCAR) supplementation. Utilizing neonatal rat hippocampal slice cultures we found that oxygen glucose deprivation (OGD) decreased the levels of free carnitines (FC) and increased the acylcarnitine (AC): FC ratio. These changes in carnitine homeostasis correlated with decreases in the protein levels of carnitine palmitoyl transferase (CPT) 1 and 2. LCAR supplementation prevented the decrease in CPT1 and CPT2, enhanced both FC and the AC∶FC ratio and increased slice culture metabolic viability, the mitochondrial membrane potential prior to OGD and prevented the subsequent loss of neurons during later stages of reperfusion through a reduction in apoptotic cell death. Finally, we found that LCAR supplementation preserved the structural integrity and synaptic transmission within the hippocampus after OGD. Thus, we conclude that LCAR supplementation preserves the key enzymes responsible for maintaining carnitine homeostasis and preserves both cell viability and synaptic transmission after OGD. PMID:22984394

  19. Role of fibroblast growth factor 19 in the control of glucose homeostasis

    NARCIS (Netherlands)

    Schaap, Frank G.

    2012-01-01

    Purpose of review Fibroblast growth factor 19 (FGF19) is a postprandial hormone released from the small intestine. FGF19 improves glucose tolerance when overexpressed in mice with impaired glucose tolerance or diabetes. This review summarizes the recent advances in our understanding of the biology

  20. Brown adipose tissue improves whole-body glucose homeostasis and insulin sensitivity in humans

    Science.gov (United States)

    Brown adipose tissue (BAT) has attracted scientific interest as an antidiabetic tissue owing to its ability to dissipate energy as heat. Despite a plethora of data concerning the role of BAT in glucose metabolism in rodents, the role of BAT (if any) in glucose metabolism in humans remains unclear. T...

  1. Effect of somatostatin on glucose homeostasis in conscious long-fasted dogs

    International Nuclear Information System (INIS)

    Stevenson, R.W.; Steiner, K.E.; Hendrick, G.K.; Cherrington, A.D.

    1987-01-01

    The effects of somatostatin plus intraportal insulin and glucagon replacement (pancreatic clamp) on carbohydrate metabolism were studied in conscious dogs fasted for 7 days so that gluconeogenesis was a major contributor to total glucose production. By use of [3- 3 H]glucose, glucose production (R a ) and utilization (R d ) and glucose clearance were assessed before and after implementation of the pancreatic clamp. After an initial control period, somatostatin (0.8 μg·kg -1 ·min -1 ) was infused with intraportal replacement amounts of glucagon and insulin. The insulin infusion rate was varied to maintain euglycemia and then kept constant for 250 min. Plasma glucagon was similar before and during somatostatin infusion, while plasma insulin was lower. Plasma glucose levels remained similar while R a and R d and the ratio of glucose clearance to plasma insulin were significantly increased. Net hepatic lactate uptake and [ 14 C]alanine plus [ 14 C]lactate conversion to [ 14 C]glucose increased. In conclusion, somatostatin alters glucose clearance in 7-day fasted dogs, resulting in changes in several indices of carbohydrate metabolism

  2. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

    NARCIS (Netherlands)

    Dupuis, J.; Langenberg, C.; Prokopenko, I.; Saxena, R.; Soranzo, N.; Jackson, A.U.; Wheeler, E.; Glazer, N.L.; Bouatia-Naji, N.; Gloyn, A.L.; Lindgren, C.M.; Mägi, R.; Morris, A.P.; Randall, J.; Johnson, T.; Hottenga, J.J.; de Geus, E.J.C.; Kaprio, J.; Kyvik, K.O.; Pedersen, N.L.; Perola, M.; Posthuma, D.; Rivadeneira, F.; Uitterlinden, A.G.; Willems van Dijk, K.; van Hoek, M.; Vogelzangs, N.; Willemsen, G.; Witteman, J.C.M.; Zillikens, M.C.; Penninx, B.W.J.H.; Boomsma, D.I.; van Duijn, C.M.; Aulchenko, Y.S.; Waterworth, D.; Vollenweider, P.; Peltonen, L.; Mooser, V.; Abecasis, G.R.; Wareham, N.J.; Sladek, R.; Froguel, P.; Watanabe, R.M.; Meigs, J.B.; Groop, L.C.; Boehnke, M.; McCarthy, M.I.; Florez, J.C.; Barroso, I.

    2010-01-01

    Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up

  3. Acute activation of GLP-1-expressing neurons promotes glucose homeostasis and insulin sensitivity

    Directory of Open Access Journals (Sweden)

    Xuemei Shi

    2017-11-01

    Conclusions: We conclude that acute activation of PPG neurons in the brainstem reduces basal glucose production, enhances intraperitoneal glucose tolerance, and augments hepatic insulin sensitivity, suggesting an important physiological role of PPG neurons-mediated circuitry in promoting glycemic control and insulin sensitivity.

  4. The Effect of Selenium Supplementation on Glucose Homeostasis and the Expression of Genes Related to Glucose Metabolism

    Directory of Open Access Journals (Sweden)

    Ewa Jablonska

    2016-12-01

    Full Text Available The aim of the study was to evaluate the effect of selenium supplementation on the expression of genes associated with glucose metabolism in humans, in order to explain the unclear relationship between selenium and the risk of diabetes. For gene expression analysis we used archival samples of cDNA from 76 non-diabetic subjects supplemented with selenium in the previous study. The supplementation period was six weeks and the daily dose of selenium was 200 µg (as selenium yeast. Blood for mRNA isolation was collected at four time points: before supplementation, after two and four weeks of supplementation, and after four weeks of washout. The analysis included 15 genes encoding selected proteins involved in insulin signaling and glucose metabolism. In addition, HbA1c and fasting plasma glucose were measured at three and four time points, respectively. Selenium supplementation was associated with a significantly decreased level of HbA1c but not fasting plasma glucose (FPG and significant down-regulation of seven genes: INSR, ADIPOR1, LDHA, PDHA, PDHB, MYC, and HIF1AN. These results suggest that selenium may affect glycemic control at different levels of regulation, linked to insulin signaling, glycolysis, and pyruvate metabolism. Further research is needed to investigate mechanisms of such transcriptional regulation and its potential implication in direct metabolic effects.

  5. Reviewing the Effects of l-Leucine Supplementation in the Regulation of Food Intake, Energy Balance, and Glucose Homeostasis

    Directory of Open Access Journals (Sweden)

    João A.B. Pedroso

    2015-05-01

    Full Text Available Leucine is a well-known activator of the mammalian target of rapamycin (mTOR. Because mTOR signaling regulates several aspects of metabolism, the potential of leucine as a dietary supplement for treating obesity and diabetes mellitus has been investigated. The objective of the present review was to summarize and discuss the available evidence regarding the mechanisms and the effects of leucine supplementation on the regulation of food intake, energy balance, and glucose homeostasis. Based on the available evidence, we conclude that although central leucine injection decreases food intake, this effect is not well reproduced when leucine is provided as a dietary supplement. Consequently, no robust evidence indicates that oral leucine supplementation significantly affects food intake, although several studies have shown that leucine supplementation may help to decrease body adiposity in specific conditions. However, more studies are necessary to assess the effects of leucine supplementation in already-obese subjects. Finally, although several studies have found that leucine supplementation improves glucose homeostasis, the underlying mechanisms involved in these potential beneficial effects remain unknown and may be partially dependent on weight loss.

  6. A whole-body model for glycogen regulation reveals a critical role for substrate cycling in maintaining blood glucose homeostasis.

    Directory of Open Access Journals (Sweden)

    Ke Xu

    2011-12-01

    Full Text Available Timely, and sometimes rapid, metabolic adaptation to changes in food supply is critical for survival as an organism moves from the fasted to the fed state, and vice versa. These transitions necessitate major metabolic changes to maintain energy homeostasis as the source of blood glucose moves away from ingested carbohydrates, through hepatic glycogen stores, towards gluconeogenesis. The integration of hepatic glycogen regulation with extra-hepatic energetics is a key aspect of these adaptive mechanisms. Here we use computational modeling to explore hepatic glycogen regulation under fed and fasting conditions in the context of a whole-body model. The model was validated against previous experimental results concerning glycogen phosphorylase a (active and glycogen synthase a dynamics. The model qualitatively reproduced physiological changes that occur during transition from the fed to the fasted state. Analysis of the model reveals a critical role for the inhibition of glycogen synthase phosphatase by glycogen phosphorylase a. This negative regulation leads to high levels of glycogen synthase activity during fasting conditions, which in turn increases substrate (futile cycling, priming the system for a rapid response once an external source of glucose is restored. This work demonstrates that a mechanistic understanding of the design principles used by metabolic control circuits to maintain homeostasis can benefit from the incorporation of mathematical descriptions of these networks into "whole-body" contextual models that mimic in vivo conditions.

  7. Clinical assessment of blood glucose homeostasis in horses: comparison of a continuous glucose monitoring system with a combined intravenous glucose and insulin test protocol.

    Science.gov (United States)

    Johnson, P J; Wiedmeyer, C E; LaCarrubba, A; Messer, N T; Dingfelder, H A; Cogswell, A M; Amorim, J R R; Ganjam, V K

    2011-01-01

    The combined glucose-insulin test (CGIT) is helpful for evaluating insulin sensitivity. A continuous glucose monitoring system (CGMS) reports changes in interstitial glucose concentrations as they occur in the blood. Use of the CGMS minimizes animal contact and may be useful when performing a CGIT. Results obtained using a CGMS are useful for the evaluation of glucose responses during the evaluation of insulin sensitivity in equids. Seven mature, obese ponies. Ponies were equipped with CGMS for determination of interstitial glucose concentrations. Glucose (150 mg/kg, i.v.) and insulin (0.1 U/kg, i.v.) were administered and blood glucose concentrations determined at (minutes after time zero) 1, 5, 15, 25, 35, 45, 60, 75, 90, 105, and 120 with a hand-held glucometer. Blood chemistry results were compared with simultaneously obtained results using CGMS. Concordance coefficients determined for comparison of blood glucose concentrations determined by a hand-held glucometer and those determined by CGMS after the zero time point were 0.623, 0.764, 0.834, 0.854, and 0.818 (for delays of 0, 5, 10, 15, and 20 minutes, respectively). Interstitial glucose concentrations obtained by the CGMS compared favorably to blood glucose concentrations. CGMS may be useful for assessment of glucose dynamics in the CGIT. Copyright © 2010 by the American College of Veterinary Internal Medicine.

  8. Impact of gain-of-function mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) on glucose and lipid homeostasis

    DEFF Research Database (Denmark)

    Foer, D; Zhu, M; Cardone, R L

    2017-01-01

    potentially represents a target for drug discovery in type 2 diabetes and hyperlipidemia. Studies in animal models suggest a physiologic link between LRP5 and glucose and lipid homeostasis; however, whether it plays a similar role in humans is unclear. As current literature links loss-of-function LRP5...... to impaired glucose and lipid metabolism, we hypothesized that individuals with an HBM-causing mutation in LRP5 would exhibit improved glucose and lipid homeostasis. Since studies in animal models have suggested that Wnt signaling augments insulin secretion, we also examined the effect of Wnt signaling...... on glucose-stimulated insulin secretion on human pancreatic islets. METHODS: This was a matched case-control study. We used several methods to assess glucose and lipid metabolism in 11 individuals with HBM-causing mutations in LRP5. Affected study participants were recruited from previously identified...

  9. Maintenance of Glucose Homeostasis through Acetylation of the Metabolic Transcriptional Coactivator PGC-1alpha

    National Research Council Canada - National Science Library

    Puigserver, Pere

    2008-01-01

    The main purpose of this proposal is to test the hypothesis that acetylation of PGC-1alpha by GCN5 and associated proteins, Pc3 and WDR18, is a key regulatory modification that controls hepatic glucose production...

  10. Central serotonergic neurons activate and recruit thermogenic brown and beige fat and regulate glucose and lipid homeostasis.

    Science.gov (United States)

    McGlashon, Jacob M; Gorecki, Michelle C; Kozlowski, Amanda E; Thirnbeck, Caitlin K; Markan, Kathleen R; Leslie, Kirstie L; Kotas, Maya E; Potthoff, Matthew J; Richerson, George B; Gillum, Matthew P

    2015-05-05

    Thermogenic brown and beige adipocytes convert chemical energy to heat by metabolizing glucose and lipids. Serotonin (5-HT) neurons in the CNS are essential for thermoregulation and accordingly may control metabolic activity of thermogenic fat. To test this, we generated mice in which the human diphtheria toxin receptor (DTR) was selectively expressed in central 5-HT neurons. Treatment with diphtheria toxin (DT) eliminated 5-HT neurons and caused loss of thermoregulation, brown adipose tissue (BAT) steatosis, and a >50% decrease in uncoupling protein 1 (Ucp1) expression in BAT and inguinal white adipose tissue (WAT). In parallel, blood glucose increased 3.5-fold, free fatty acids 13.4-fold, and triglycerides 6.5-fold. Similar BAT and beige fat defects occurred in Lmx1b(f/f)ePet1(Cre) mice in which 5-HT neurons fail to develop in utero. We conclude 5-HT neurons play a major role in regulating glucose and lipid homeostasis, in part through recruitment and metabolic activation of brown and beige adipocytes. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Effects of Bisphenol A on glucose homeostasis and brain insulin signaling pathways in male mice.

    Science.gov (United States)

    Fang, Fangfang; Chen, Donglong; Yu, Pan; Qian, Wenyi; Zhou, Jing; Liu, Jingli; Gao, Rong; Wang, Jun; Xiao, Hang

    2015-02-01

    The potential effects of Bisphenol A (BPA) on peripheral insulin resistance have recently gained more attention, however, its functions on brain insulin resistance are still unknown. The aim of the present study was to investigate the effects of BPA on insulin signaling and glucose transport in mouse brain. The male mice were administrated of 100 μg/kg/day BPA or vehicle for 15 days then challenged with glucose and insulin tolerance tests. The insulin levels were detected with radioimmunoassay (RIA), and the insulin signaling pathways were investigated by Western blot. Our results revealed that BPA significantly increased peripheral plasma insulin levels, and decreased the insulin signals including phosphorylated insulin receptor (p-IR), phosphorylated insulin receptor substrate 1 (p-IRS1), phosphorylated protein kinase B (p-AKT), phosphorylated glycogen synthase kinase 3β (p-GSK3β) and phosphorylated extracellular regulated protein kinases (p-ERK1/2) in the brain, though insulin expression in both hippocampus and profrontal cortex was increased. In parallel, BPA exposure might contribute to glucose transport disturbance in the brain since the expression of glucose transporters were markedly decreased. In conclusion, BPA exposure perturbs the insulin signaling and glucose transport in the brain, therefore, it might be a risk factor for brain insulin resistance. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Effect of somatostatin on nonesterified fatty acid levels modifies glucose homeostasis during fasting

    International Nuclear Information System (INIS)

    Hendrick, G.K.; Frizzell, R.T.; Cherrington, A.D.

    1987-01-01

    In the 7-days fasted conscious dog, unlike the postabsorptive conscious dog, somatostatin infusion results in decreased levels of nonesterified fatty acids (NEFA) and increased glucose utilization (R d ) even when insulin and glucagon levels are held constant. The aim of this study was to determine whether NEFA replacement in such animals would prevent the increase in R d . In each of three protocols there was an 80-min tracer equilibration period, a 40-min basal period, and a 3-h test period. During the test period in the first protocol saline was infused, in the second protocol somatostatin was infused along with intraportal replacement amounts of insulin and glucagon (hormone replacement), while in the third protocol somatostatin plus the pancreatic hormones were infused with concurrent heparin plus Intralipid infusion. Glucose turnover was assessed using [3- 3 H]glucose. The peripheral levels of insulin, glucagon, and glucose were similar and constant in all three protocols; however, during somatostatin infusion, exogenous glucose infusion was necessary to maintain euglycemia. The NEFA level was constant during saline infusion and decreased in the hormone replacement protocol. In the hormone replacement plus NEFA protocol, the NEFA level did not change during the first 90-min period and then increased during the second 90-min period. After a prolonged fast in the dog, (1) somatostatin directly or indirectly inhibits adipose tissue NEFA release and causes a decrease in the plasma NEFA level, and (2) this decrease in the NEFA level causes an increase in R d

  13. Farnesoid X receptor: a master regulator of hepatic triglyceride and glucose homeostasis

    Science.gov (United States)

    Jiao, Yang; Lu, Yan; Li, Xiao-ying

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) is characterized by the aberrant accumulation of triglycerides in hepatocytes in the absence of significant alcohol consumption, viral infection or other specific causes of liver disease. NAFLD has become a burgeoning health problem both worldwide and in China, but its pathogenesis remains poorly understood. Farnesoid X receptor (FXR), a member of the nuclear receptor (NR) superfamily, has been demonstrated to be the primary sensor for endogenous bile acids, and play a crucial role in hepatic triglyceride homeostasis. Deciphering the synergistic contributions of FXR to triglyceride metabolism is critical for discovering therapeutic agents in the treatment of NAFLD and hypertriglyceridemia. PMID:25500875

  14. Combined heart rate- and accelerometer-assessed physical activity energy expenditure and associations with glucose homeostasis markers in a population at high risk of developing diabetes

    DEFF Research Database (Denmark)

    Hansen, Anne-Louise Smidt; Carstensen, Bendix; Helge, Jørn Wulff

    2013-01-01

    OBJECTIVE: Regular physical activity (PA) reduces the risk of developing type 2 diabetes, and different subtypes of dysglycemia have shown different associations with PA. To better understand the associations of PA and glucose homeostasis, we examined the association of objectively measured PA...... energy expenditure (PAEE) with detailed measures of glucose homeostasis. RESEARCH DESIGN AND METHODS: In 1,531 men and women, with low to high risk of developing type 2 diabetes, we measured 7 days of PAEE using a combined accelerometry and heart rate monitor (ActiHeart). Measures and indices of glucose...... of PAEE slightly in an entire population at risk for developing type 2 diabetes may be a realistic and worthwhile goal to reach in order to achieve beneficial effect in terms of glucose metabolism....

  15. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

    DEFF Research Database (Denmark)

    Dupuis, Josée; Langenberg, Claudia; Prokopenko, Inga

    2010-01-01

    Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up...... to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA......2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell...

  16. Magnesium deficiency improves glucose homeostasis in the rat: studies in vivo and in isolated islets in vitro.

    Science.gov (United States)

    Reis, M A; Latorraca, M Q; Carneiro, E M; Boschero, A C; Saad, M J; Velloso, L A; Reyes, F G

    2001-05-01

    The serum mineral levels, glucose disappearance rate (kg), total area under the glucose (DeltaG) and insulin (DeltaI) curves, and static insulin secretion were compared among rats fed a Mg-deficient diet for 6 (DF-6) or 11 (DF-11) weeks, and rats fed a control diet for the same periods (CO-6 and CO-11 groups). No change in glucose homeostasis was observed among DF-6, CO-6 and CO-11 rats. DF-11 rats showed an elevated kg and a reduced DeltaG and DeltaI. For evaluating the effect of supplementation, rats fed a control or Mg-deficient diet for 6 weeks were then fed a Mg- supplemented diet for 5 weeks (SCO and SDF groups respectively). The serum Mg levels in SDF rats were similar to those in CO-11 and SCO rats, but higher than in the DF-11 group. SDF rats showed similar kg, DeltaG and DeltaI compared with the CO-11 and SCO groups. However, a significantly lower kg and higher DeltaG and DeltaI were observed in SDF compared with DF-11 rats. Basal and 8.3 mmol glucose/l-stimulated insulin secretion by islets from DF-11 rats were higher than by islets from CO-11 rats. These results indicate that moderate Mg depletion for a long period may increase the secretion and sensitivity to insulin, while Mg supplementation in formerly Mg-deficient rats may prevent the increase in sensitivity and secretion of insulin.

  17. Neuronal calcium sensor synaptotagmin-9 is not involved in the regulation of glucose homeostasis or insulin secretion.

    Directory of Open Access Journals (Sweden)

    Natalia Gustavsson

    Full Text Available BACKGROUND: Insulin secretion is a complex and highly regulated process. It is well established that cytoplasmic calcium is a key regulator of insulin secretion, but how elevated intracellular calcium triggers insulin granule exocytosis remains unclear, and we have only begun to define the identities of proteins that are responsible for sensing calcium changes and for transmitting the calcium signal to release machineries. Synaptotagmins are primarily expressed in brain and endocrine cells and exhibit diverse calcium binding properties. Synaptotagmin-1, -2 and -9 are calcium sensors for fast neurotransmitter release in respective brain regions, while synaptotagmin-7 is a positive regulator of calcium-dependent insulin release. Unlike the three neuronal calcium sensors, whose deletion abolished fast neurotransmitter release, synaptotagmin-7 deletion resulted in only partial loss of calcium-dependent insulin secretion, thus suggesting that other calcium-sensors must participate in the regulation of insulin secretion. Of the other synaptotagmin isoforms that are present in pancreatic islets, the neuronal calcium sensor synaptotagmin-9 is expressed at the highest level after synaptotagmin-7. METHODOLOGY/PRINCIPAL FINDINGS: In this study we tested whether synaptotagmin-9 participates in the regulation of glucose-stimulated insulin release by using pancreas-specific synaptotagmin-9 knockout (p-S9X mice. Deletion of synaptotagmin-9 in the pancreas resulted in no changes in glucose homeostasis or body weight. Glucose tolerance, and insulin secretion in vivo and from isolated islets were not affected in the p-S9X mice. Single-cell capacitance measurements showed no difference in insulin granule exocytosis between p-S9X and control mice. CONCLUSIONS: Thus, synaptotagmin-9, although a major calcium sensor in the brain, is not involved in the regulation of glucose-stimulated insulin release from pancreatic β-cells.

  18. Neuronal calcium sensor synaptotagmin-9 is not involved in the regulation of glucose homeostasis or insulin secretion.

    Science.gov (United States)

    Gustavsson, Natalia; Wang, Xiaorui; Wang, Yue; Seah, Tingting; Xu, Jun; Radda, George K; Südhof, Thomas C; Han, Weiping

    2010-11-09

    Insulin secretion is a complex and highly regulated process. It is well established that cytoplasmic calcium is a key regulator of insulin secretion, but how elevated intracellular calcium triggers insulin granule exocytosis remains unclear, and we have only begun to define the identities of proteins that are responsible for sensing calcium changes and for transmitting the calcium signal to release machineries. Synaptotagmins are primarily expressed in brain and endocrine cells and exhibit diverse calcium binding properties. Synaptotagmin-1, -2 and -9 are calcium sensors for fast neurotransmitter release in respective brain regions, while synaptotagmin-7 is a positive regulator of calcium-dependent insulin release. Unlike the three neuronal calcium sensors, whose deletion abolished fast neurotransmitter release, synaptotagmin-7 deletion resulted in only partial loss of calcium-dependent insulin secretion, thus suggesting that other calcium-sensors must participate in the regulation of insulin secretion. Of the other synaptotagmin isoforms that are present in pancreatic islets, the neuronal calcium sensor synaptotagmin-9 is expressed at the highest level after synaptotagmin-7. In this study we tested whether synaptotagmin-9 participates in the regulation of glucose-stimulated insulin release by using pancreas-specific synaptotagmin-9 knockout (p-S9X) mice. Deletion of synaptotagmin-9 in the pancreas resulted in no changes in glucose homeostasis or body weight. Glucose tolerance, and insulin secretion in vivo and from isolated islets were not affected in the p-S9X mice. Single-cell capacitance measurements showed no difference in insulin granule exocytosis between p-S9X and control mice. Thus, synaptotagmin-9, although a major calcium sensor in the brain, is not involved in the regulation of glucose-stimulated insulin release from pancreatic β-cells.

  19. Role of FAT/CD36 in fatty acid sensing, energy, and glucose homeostasis regulation in DIO and DR rats.

    Science.gov (United States)

    Le Foll, Christelle; Dunn-Meynell, Ambrose A; Levin, Barry E

    2015-02-01

    Hypothalamic fatty acid (FA) sensing neurons alter their activity utilizing the FA translocator/receptor, FAT/CD36. Depletion of ventromedial hypothalamus (VMH) CD36 with adeno-associated viral vector expressing CD36 shRNA (AAV CD36 shRNA) leads to redistribution of adipose stores and insulin resistance in outbred rats. This study assessed the requirement of VMH CD36-mediated FA sensing for the regulation of energy and glucose homeostasis in postnatal day 5 (P5) and P21 selectively bred diet-induced obese (DIO) and diet-resistant (DR) rats using VMH AAV CD36 shRNA injections. P5 CD36 depletion altered VMH neuronal FA sensing predominantly in DIO rats. After 10 wk on a 45% fat diet, DIO rats injected with VMH AAV CD36 shRNA at P21 ate more and gained more weight than DIO AAV controls, while DR AAV CD36 shRNA-injected rats gained less weight than DR AAV controls. VMH CD36 depletion increased inguinal fat pad weights and leptin levels in DIO and DR rats. Although DR AAV CD36 shRNA-injected rats became as obese as DIO AAV controls, only DIO control and CD36 depleted rats became insulin-resistant on a 45% fat diet. VMH CD36 depletion stunted linear growth in DIO and DR rats. DIO rats injected with AAV CD36 shRNA at P5 had increased fat mass, mostly due to a 45% increase in subcutaneous fat. They were also insulin-resistant with an associated 71% increase of liver triglycerides. These results demonstrate that VMH CD36-mediated FA sensing is a critical factor in the regulation of energy and glucose homeostasis and fat deposition in DIO and DR rats.

  20. Lupanine Improves Glucose Homeostasis by Influencing KATP Channels and Insulin Gene Expression

    Directory of Open Access Journals (Sweden)

    Mats Wiedemann

    2015-10-01

    Full Text Available The glucose-lowering effects of lupin seeds involve the combined action of several components. The present study investigates the influence of one of the main quinolizidine alkaloids, lupanine, on pancreatic beta cells and in an animal model of type-2 diabetes mellitus. In vitro studies were performed with insulin-secreting INS-1E cells or islets of C57BL/6 mice. In the in vivo experiments, hyperglycemia was induced in rats by injecting streptozotocin (65 mg/kg body weight. In the presence of 15 mmol/L glucose, insulin secretion was significantly elevated by 0.5 mmol/L lupanine, whereas the alkaloid did not stimulate insulin release with lower glucose concentrations. In islets treated with l-arginine, the potentiating effect of lupanine already occurred at 8 mmol/L glucose. Lupanine increased the expression of the Ins-1 gene. The potentiating effect on secretion was correlated to membrane depolarization and an increase in the frequency of Ca2+ action potentials. Determination of the current through ATP-dependent K+ channels (KATP channels revealed that lupanine directly inhibited the channel. The effect was dose-dependent but, even with a high lupanine concentration of 1 mmol/L or after a prolonged exposure time (12 h, the KATP channel block was incomplete. Oral administration of lupanine did not induce hypoglycemia. By contrast, lupanine improved glycemic control in response to an oral glucose tolerance test in streptozotocin-diabetic rats. In summary, lupanine acts as a positive modulator of insulin release obviously without a risk for hypoglycemic episodes.

  1. The Proton-Activated Receptor GPR4 Modulates Glucose Homeostasis by Increasing Insulin Sensitivity

    Directory of Open Access Journals (Sweden)

    Luca Giudici

    2013-11-01

    Full Text Available Background: The proton-activated G protein-coupled receptor GPR4 is expressed in many tissues including white adipose tissue. GPR4 is activated by extracellular protons in the physiological pH range (i.e. pH 7.7 - 6.8 and is coupled to the production of cAMP. Methods: We examined mice lacking GPR4 and examined glucose tolerance and insulin sensitivity in young and aged mice as well as in mice fed with a high fat diet. Expression profiles of pro- and anti-inflammatory cytokines in white adipose tissue, liver and skeletal muscle was assessed. Results: Here we show that mice lacking GPR4 have an improved intraperitoneal glucose tolerance test and increased insulin sensitivity. Insulin levels were comparable but leptin levels were increased in GPR4 KO mice. Gpr4-/- showed altered expression of PPARα, IL-6, IL-10, TNFα, and TGF-1β in skeletal muscle, white adipose tissue, and liver. High fat diet abolished the differences in glucose tolerance and insulin sensitivity between Gpr4+/+ and Gpr4-/- mice. In contrast, in aged mice (12 months old, the positive effect of GPR4 deficiency on glucose tolerance and insulin sensitivity was maintained. Liver and adipose tissue showed no major differences in the mRNA expression of pro- and anti-inflammatory factors between aged mice of both genotypes. Conclusion: Thus, GPR4 deficiency improves glucose tolerance and insulin sensitivity. The effect may involve an altered balance between pro- and anti-inflammatory factors in insulin target tissues.

  2. Bisphenol A, phthalate metabolites and glucose homeostasis in healthy normal-weight children

    DEFF Research Database (Denmark)

    Carlsson, Amalie; Sørensen, Kaspar; Andersson, Anna-Maria

    2018-01-01

    . RESULTS: Children in the lowest tertile of urinary BPA had significantly higher peak insulin levels during OGTT (P = 0.01), lower insulin sensitivity index (P triglyceride (P ... toward higher fat mass index (P = 0.1) compared with children in the highest tertile for uBPA. No significant differences in anthropometrics, body composition or glucose metabolism were associated with any of the phthalate metabolites measured. CONCLUSION: This pilot study on healthy normal...... and adolescents. METHOD: This was a cross-sectional study. Participants were recruited as part of the Copenhagen Puberty Study. The subjects were evaluated by an oral glucose tolerance test (OGTT), a dual-energy X-ray absorptiometry (DXA) scan, direct oxygen uptake measurement during cycle ergometry and fasting...

  3. Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system.

    Science.gov (United States)

    Arriola Apelo, Sebastian I; Neuman, Joshua C; Baar, Emma L; Syed, Faizan A; Cummings, Nicole E; Brar, Harpreet K; Pumper, Cassidy P; Kimple, Michelle E; Lamming, Dudley W

    2016-02-01

    Inhibition of the mechanistic target of rapamycin (mTOR) signaling pathway by the FDA-approved drug rapamycin has been shown to promote lifespan and delay age-related diseases in model organisms including mice. Unfortunately, rapamycin has potentially serious side effects in humans, including glucose intolerance and immunosuppression, which may preclude the long-term prophylactic use of rapamycin as a therapy for age-related diseases. While the beneficial effects of rapamycin are largely mediated by the inhibition of mTOR complex 1 (mTORC1), which is acutely sensitive to rapamycin, many of the negative side effects are mediated by the inhibition of a second mTOR-containing complex, mTORC2, which is much less sensitive to rapamycin. We hypothesized that different rapamycin dosing schedules or the use of FDA-approved rapamycin analogs with different pharmacokinetics might expand the therapeutic window of rapamycin by more specifically targeting mTORC1. Here, we identified an intermittent rapamycin dosing schedule with minimal effects on glucose tolerance, and we find that this schedule has a reduced impact on pyruvate tolerance, fasting glucose and insulin levels, beta cell function, and the immune system compared to daily rapamycin treatment. Further, we find that the FDA-approved rapamycin analogs everolimus and temsirolimus efficiently inhibit mTORC1 while having a reduced impact on glucose and pyruvate tolerance. Our results suggest that many of the negative side effects of rapamycin treatment can be mitigated through intermittent dosing or the use of rapamycin analogs. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  4. A dual role of lipasin (betatrophin) in lipid metabolism and glucose homeostasis: consensus and controversy

    OpenAIRE

    Zhang, Ren; Abou-Samra, Abdul B

    2014-01-01

    Metabolic syndrome includes glucose intolerance and dyslipidemia, both of which are strong risk factors for developing diabetes and atherosclerotic cardiovascular diseases. Recently, multiple groups independently studied a previously uncharacterized gene, officially named C19orf80 (human) and Gm6484 (mouse), but more commonly known as RIFL, Angptl8, betatrophin and lipasin. Both exciting and conflicting results have been obtained, and significant controversy is ongoing. Accumulating evidence ...

  5. Ambient Air Pollutants Have Adverse Effects on Insulin and Glucose Homeostasis in Mexican Americans

    Science.gov (United States)

    Chen, Zhanghua; Salam, Muhammad T.; Toledo-Corral, Claudia; Watanabe, Richard M.; Xiang, Anny H.; Buchanan, Thomas A.; Habre, Rima; Bastain, Theresa M.; Lurmann, Fred; Wilson, John P.; Trigo, Enrique

    2016-01-01

    OBJECTIVE Recent studies suggest that air pollution plays a role in type 2 diabetes (T2D) incidence and mortality. The underlying physiological mechanisms have yet to be established. We hypothesized that air pollution adversely affects insulin sensitivity and secretion and serum lipid levels. RESEARCH DESIGN AND METHODS Participants were selected from BetaGene (n = 1,023), a study of insulin resistance and pancreatic β-cell function in Mexican Americans. All participants underwent DXA and oral and intravenous glucose tolerance tests and completed dietary and physical activity questionnaires. Ambient air pollutant concentrations (NO2, O3, and PM2.5) for short- and long-term periods were assigned by spatial interpolation (maximum interpolation radius of 50 km) of data from air quality monitors. Traffic-related air pollution from freeways (TRAP) was estimated using the dispersion model as NOx. Variance component models were used to analyze individual and multiple air pollutant associations with metabolic traits. RESULTS Short-term (up to 58 days cumulative lagged averages) exposure to PM2.5 was associated with lower insulin sensitivity and HDL-to-LDL cholesterol ratio and higher fasting glucose and insulin, HOMA-IR, total cholesterol, and LDL cholesterol (LDL-C) (all P ≤ 0.036). Annual average PM2.5 was associated with higher fasting glucose, HOMA-IR, and LDL-C (P ≤ 0.043). The effects of short-term PM2.5 exposure on insulin sensitivity were largest among obese participants. No statistically significant associations were found between TRAP and metabolic outcomes. CONCLUSIONS Exposure to ambient air pollutants adversely affects glucose tolerance, insulin sensitivity, and blood lipid concentrations. Our findings suggest that ambient air pollutants may contribute to the pathophysiology in the development of T2D and related sequelae. PMID:26868440

  6. Neuronal Rap1 regulates energy balance, glucose homeostasis, and leptin actions

    OpenAIRE

    Kaneko, Kentaro; Xu, Pingwen; Cordonier, Elizabeth L.; Chen, Siyu S.; Ng, Amy; Xu, Yong; Morozov, Alexei; Fukuda, Makoto

    2016-01-01

    The central nervous system (CNS) contributes to obesity and metabolic disease; however, the underlying neurobiological pathways remain to be fully established. Here we show that the small GTPase Rap1 is expressed in multiple hypothalamic nuclei that control whole-body metabolism and is activated in high-fat diet (HFD)-induced obesity. Genetic ablation of CNS Rap1 protects mice from dietary obesity, glucose imbalance, and insulin resistance in the periphery and from HFD-induced neuropathologic...

  7. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

    Science.gov (United States)

    Dupuis, Josée; Langenberg, Claudia; Prokopenko, Inga; Saxena, Richa; Soranzo, Nicole; Jackson, Anne U; Wheeler, Eleanor; Glazer, Nicole L; Bouatia-Naji, Nabila; Gloyn, Anna L; Lindgren, Cecilia M; Mägi, Reedik; Morris, Andrew P; Randall, Joshua; Johnson, Toby; Elliott, Paul; Rybin, Denis; Thorleifsson, Gudmar; Steinthorsdottir, Valgerdur; Henneman, Peter; Grallert, Harald; Dehghan, Abbas; Hottenga, Jouke Jan; Franklin, Christopher S; Navarro, Pau; Song, Kijoung; Goel, Anuj; Perry, John R B; Egan, Josephine M; Lajunen, Taina; Grarup, Niels; Sparsø, Thomas; Doney, Alex; Voight, Benjamin F; Stringham, Heather M; Li, Man; Kanoni, Stavroula; Shrader, Peter; Cavalcanti-Proença, Christine; Kumari, Meena; Qi, Lu; Timpson, Nicholas J; Gieger, Christian; Zabena, Carina; Rocheleau, Ghislain; Ingelsson, Erik; An, Ping; O’Connell, Jeffrey; Luan, Jian'an; Elliott, Amanda; McCarroll, Steven A; Payne, Felicity; Roccasecca, Rosa Maria; Pattou, François; Sethupathy, Praveen; Ardlie, Kristin; Ariyurek, Yavuz; Balkau, Beverley; Barter, Philip; Beilby, John P; Ben-Shlomo, Yoav; Benediktsson, Rafn; Bennett, Amanda J; Bergmann, Sven; Bochud, Murielle; Boerwinkle, Eric; Bonnefond, Amélie; Bonnycastle, Lori L; Borch-Johnsen, Knut; Böttcher, Yvonne; Brunner, Eric; Bumpstead, Suzannah J; Charpentier, Guillaume; Chen, Yii-Der Ida; Chines, Peter; Clarke, Robert; Coin, Lachlan J M; Cooper, Matthew N; Cornelis, Marilyn; Crawford, Gabe; Crisponi, Laura; Day, Ian N M; de Geus, Eco; Delplanque, Jerome; Dina, Christian; Erdos, Michael R; Fedson, Annette C; Fischer-Rosinsky, Antje; Forouhi, Nita G; Fox, Caroline S; Frants, Rune; Franzosi, Maria Grazia; Galan, Pilar; Goodarzi, Mark O; Graessler, Jürgen; Groves, Christopher J; Grundy, Scott; Gwilliam, Rhian; Gyllensten, Ulf; Hadjadj, Samy; Hallmans, Göran; Hammond, Naomi; Han, Xijing; Hartikainen, Anna-Liisa; Hassanali, Neelam; Hayward, Caroline; Heath, Simon C; Hercberg, Serge; Herder, Christian; Hicks, Andrew A; Hillman, David R; Hingorani, Aroon D; Hofman, Albert; Hui, Jennie; Hung, Joe; Isomaa, Bo; Johnson, Paul R V; Jørgensen, Torben; Jula, Antti; Kaakinen, Marika; Kaprio, Jaakko; Kesaniemi, Y Antero; Kivimaki, Mika; Knight, Beatrice; Koskinen, Seppo; Kovacs, Peter; Kyvik, Kirsten Ohm; Lathrop, G Mark; Lawlor, Debbie A; Le Bacquer, Olivier; Lecoeur, Cécile; Li, Yun; Lyssenko, Valeriya; Mahley, Robert; Mangino, Massimo; Manning, Alisa K; Martínez-Larrad, María Teresa; McAteer, Jarred B; McCulloch, Laura J; McPherson, Ruth; Meisinger, Christa; Melzer, David; Meyre, David; Mitchell, Braxton D; Morken, Mario A; Mukherjee, Sutapa; Naitza, Silvia; Narisu, Narisu; Neville, Matthew J; Oostra, Ben A; Orrù, Marco; Pakyz, Ruth; Palmer, Colin N A; Paolisso, Giuseppe; Pattaro, Cristian; Pearson, Daniel; Peden, John F; Pedersen, Nancy L.; Perola, Markus; Pfeiffer, Andreas F H; Pichler, Irene; Polasek, Ozren; Posthuma, Danielle; Potter, Simon C; Pouta, Anneli; Province, Michael A; Psaty, Bruce M; Rathmann, Wolfgang; Rayner, Nigel W; Rice, Kenneth; Ripatti, Samuli; Rivadeneira, Fernando; Roden, Michael; Rolandsson, Olov; Sandbaek, Annelli; Sandhu, Manjinder; Sanna, Serena; Sayer, Avan Aihie; Scheet, Paul; Scott, Laura J; Seedorf, Udo; Sharp, Stephen J; Shields, Beverley; Sigurðsson, Gunnar; Sijbrands, Erik J G; Silveira, Angela; Simpson, Laila; Singleton, Andrew; Smith, Nicholas L; Sovio, Ulla; Swift, Amy; Syddall, Holly; Syvänen, Ann-Christine; Tanaka, Toshiko; Thorand, Barbara; Tichet, Jean; Tönjes, Anke; Tuomi, Tiinamaija; Uitterlinden, André G; van Dijk, Ko Willems; van Hoek, Mandy; Varma, Dhiraj; Visvikis-Siest, Sophie; Vitart, Veronique; Vogelzangs, Nicole; Waeber, Gérard; Wagner, Peter J; Walley, Andrew; Walters, G Bragi; Ward, Kim L; Watkins, Hugh; Weedon, Michael N; Wild, Sarah H; Willemsen, Gonneke; Witteman, Jaqueline C M; Yarnell, John W G; Zeggini, Eleftheria; Zelenika, Diana; Zethelius, Björn; Zhai, Guangju; Zhao, Jing Hua; Zillikens, M Carola; Borecki, Ingrid B; Loos, Ruth J F; Meneton, Pierre; Magnusson, Patrik K E; Nathan, David M; Williams, Gordon H; Hattersley, Andrew T; Silander, Kaisa; Salomaa, Veikko; Smith, George Davey; Bornstein, Stefan R; Schwarz, Peter; Spranger, Joachim; Karpe, Fredrik; Shuldiner, Alan R; Cooper, Cyrus; Dedoussis, George V; Serrano-Ríos, Manuel; Morris, Andrew D; Lind, Lars; Palmer, Lyle J; Hu, Frank B.; Franks, Paul W; Ebrahim, Shah; Marmot, Michael; Kao, W H Linda; Pankow, James S; Sampson, Michael J; Kuusisto, Johanna; Laakso, Markku; Hansen, Torben; Pedersen, Oluf; Pramstaller, Peter Paul; Wichmann, H Erich; Illig, Thomas; Rudan, Igor; Wright, Alan F; Stumvoll, Michael; Campbell, Harry; Wilson, James F; Hamsten, Anders; Bergman, Richard N; Buchanan, Thomas A; Collins, Francis S; Mohlke, Karen L; Tuomilehto, Jaakko; Valle, Timo T; Altshuler, David; Rotter, Jerome I; Siscovick, David S; Penninx, Brenda W J H; Boomsma, Dorret; Deloukas, Panos; Spector, Timothy D; Frayling, Timothy M; Ferrucci, Luigi; Kong, Augustine; Thorsteinsdottir, Unnur; Stefansson, Kari; van Duijn, Cornelia M; Aulchenko, Yurii S; Cao, Antonio; Scuteri, Angelo; Schlessinger, David; Uda, Manuela; Ruokonen, Aimo; Jarvelin, Marjo-Riitta; Waterworth, Dawn M; Vollenweider, Peter; Peltonen, Leena; Mooser, Vincent; Abecasis, Goncalo R; Wareham, Nicholas J; Sladek, Robert; Froguel, Philippe; Watanabe, Richard M; Meigs, James B; Groop, Leif; Boehnke, Michael; McCarthy, Mark I; Florez, Jose C; Barroso, Inês

    2010-01-01

    Circulating glucose levels are tightly regulated. To identify novel glycemic loci, we performed meta-analyses of 21 genome-wide associations studies informative for fasting glucose (FG), fasting insulin (FI) and indices of β-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 non-diabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with FG/HOMA-B and two associated with FI/HOMA-IR. These include nine new FG loci (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and FAM148B) and one influencing FI/HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB/TMEM195 with type 2 diabetes (T2D). Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify T2D risk loci, as well as loci that elevate FG modestly, but do not cause overt diabetes. PMID:20081858

  8. Changes in Glucose Homeostasis after Roux-en-Y Gastric Bypass Surgery for Obesity at Day Three, Two Months, and One Year after Surgery

    DEFF Research Database (Denmark)

    Falkén, Y; Hellström, P M; Holst, Jens Juul

    2011-01-01

    Context: Endocrine effects of gastric bypass (GBP) surgery for obesity on glucose homeostasis are not fully understood. Main Objective: The main objective of the study was to assess the changes in plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), leptin, somatostatin, glucose-dependent in......Context: Endocrine effects of gastric bypass (GBP) surgery for obesity on glucose homeostasis are not fully understood. Main Objective: The main objective of the study was to assess the changes in plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), leptin, somatostatin, glucose......-dependent insulinotropic peptide, enteroglucagon, and glucagon early after GBP. Method: Twelve obese subjects (body mass index 45.3 ± 1.9 kg/m2) were subjected to a liquid meal without lipids before and 3 d, 2 months, and 1 yr after GBP. Plasma concentrations of glucose, insulin, leptin, and gut peptide hormones were...... index 30.3 ± 1.8 kg/m2 at 1 yr). Fasting glucose was significantly lower on d 3 (P

  9. Glucose homeostasis in rainbow trout fed a high-carbohydrate diet: metformin and insulin interact in a tissue-dependent manner.

    Science.gov (United States)

    Polakof, S; Moon, T W; Aguirre, P; Skiba-Cassy, S; Panserat, S

    2011-01-01

    Carnivorous fish species such as the rainbow trout (Oncorhynchus mykiss) are considered to be "glucose intolerant" because of the prolonged hyperglycemia experienced after intake of a carbohydrate-enriched meal. In the present study, we use this species to study glucose homeostasis in fish chronically infused with the hypoglycemic agents, insulin, and metformin, and fed with a high proportion of carbohydrates (30%). We analyzed liver, skeletal muscle, and white adipose tissue (WAT), which are insulin- and metformin-specific targets at both the biochemical and molecular levels. Trout infused with the combination of insulin and metformin can effectively utilize dietary glucose at the liver, resulting in lowered glycemia, increased insulin sensitivity, and glucose storage capacity, combined with reduced glucose output. However, in both WAT and skeletal muscle, we observed decreased insulin sensitivity with the combined insulin + metformin treatment, resulting in the absence of changes at the metabolic level in the skeletal muscle and an increased potential for glucose uptake and storage in the WAT. Thus, the poor utilization by rainbow trout of a diet with a high proportion of carbohydrate can at least be partially improved by a combined treatment with insulin and metformin, and the glucose intolerance observed in this species could be, in part, due to some of the downstream components of the insulin and metformin signaling pathways. However, the predominant effects of metformin treatment on the action of insulin in these three tissues thought to be involved in glucose homeostasis remain exclusive in this species.

  10. Ribosomal S6K1 in POMC and AgRP Neurons Regulates Glucose Homeostasis but Not Feeding Behavior in Mice

    Directory of Open Access Journals (Sweden)

    Mark A. Smith

    2015-04-01

    Full Text Available Hypothalamic ribosomal S6K1 has been suggested as a point of convergence for hormonal and nutrient signals in the regulation of feeding behavior, bodyweight, and glucose metabolism. However, the long-term effects of manipulating hypothalamic S6K1 signaling on energy homeostasis and the cellular mechanisms underlying these roles are unclear. We therefore inactivated S6K1 in pro-opiomelanocortin (POMC and agouti-related protein (AgRP neurons, key regulators of energy homeostasis, but in contrast to the current view, we found no evidence that S6K1 regulates food intake and bodyweight. In contrast, S6K1 signaling in POMC neurons regulated hepatic glucose production and peripheral lipid metabolism and modulated neuronal excitability. S6K1 signaling in AgRP neurons regulated skeletal muscle insulin sensitivity and was required for glucose sensing by these neurons. Our findings suggest that S6K1 signaling is not a general integrator of energy homeostasis in the mediobasal hypothalamus but has distinct roles in the regulation of glucose homeostasis by POMC and AgRP neurons.

  11. Munc18b Increases Insulin Granule Fusion, Restoring Deficient Insulin Secretion in Type-2 Diabetes Human and Goto-Kakizaki Rat Islets with Improvement in Glucose Homeostasis

    Directory of Open Access Journals (Sweden)

    Tairan Qin

    2017-02-01

    Infusion of Ad-Munc18b into GK rat pancreas led to sustained improvement in glucose homeostasis. However, Munc18b overexpression in normal islets increased only newcomer SG fusion. Therefore, Munc18b could potentially be deployed in human T2D to rescue the deficient GSIS.

  12. Ribosomal S6K1 in POMC and AgRP Neurons Regulates Glucose Homeostasis but Not Feeding Behavior in Mice.

    Science.gov (United States)

    Smith, Mark A; Katsouri, Loukia; Irvine, Elaine E; Hankir, Mohammed K; Pedroni, Silvia M A; Voshol, Peter J; Gordon, Matthew W; Choudhury, Agharul I; Woods, Angela; Vidal-Puig, Antonio; Carling, David; Withers, Dominic J

    2015-04-21

    Hypothalamic ribosomal S6K1 has been suggested as a point of convergence for hormonal and nutrient signals in the regulation of feeding behavior, bodyweight, and glucose metabolism. However, the long-term effects of manipulating hypothalamic S6K1 signaling on energy homeostasis and the cellular mechanisms underlying these roles are unclear. We therefore inactivated S6K1 in pro-opiomelanocortin (POMC) and agouti-related protein (AgRP) neurons, key regulators of energy homeostasis, but in contrast to the current view, we found no evidence that S6K1 regulates food intake and bodyweight. In contrast, S6K1 signaling in POMC neurons regulated hepatic glucose production and peripheral lipid metabolism and modulated neuronal excitability. S6K1 signaling in AgRP neurons regulated skeletal muscle insulin sensitivity and was required for glucose sensing by these neurons. Our findings suggest that S6K1 signaling is not a general integrator of energy homeostasis in the mediobasal hypothalamus but has distinct roles in the regulation of glucose homeostasis by POMC and AgRP neurons. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Hibiscus rosa sinensis Linn. Petals Modulates Glycogen Metabolism and Glucose Homeostasis Signalling Pathway in Streptozotocin-Induced Experimental Diabetes.

    Science.gov (United States)

    Pillai, Sneha S; Mini, S

    2016-03-01

    The prevalence of diabetes mellitus is becoming more and more serious and reaches epidemic proportions worldwide. Scientific research is constantly looking for new agents that could be used as dietary functional ingredients in the fight against diabetes. The objective of the present study was to evaluate the effect of ethyl acetate fraction of Hibiscus rosa sinensis Linn. petals on experimental diabetes at a dose of 25 mg/kg body weight and it was compared with standard anti-diabetic drug metformin. The elevated levels of serum glucose (398.56 ± 35.78) and glycated haemoglobin (12.89 ± 1.89) in diabetic rats were significantly decreased (156.89 ± 14.45 and 6.12 ± 0.49, respectively) by Hibiscus rosa sinensis petals (EHRS) administration. Hepatotoxicity marker enzyme levels in serum were normalized. The fraction supplementation restored the glycogen content by regulating the activities of glycogen metabolizing enzymes. It significantly modulated the expressions of marker genes involved in glucose homeostasis signalling pathway. Histopathological analysis of liver and pancreas supported our findings. The overall effect was comparable with metformin. Hence, our study reveals the role of hibiscus petals for alleviation of diabetes complications, thus it can be propagated as a nutraceutical agent.

  14. Nuclear and Membrane Actions of Estrogen Receptor Alpha: Contribution to the Regulation of Energy and Glucose Homeostasis.

    Science.gov (United States)

    Guillaume, Maeva; Montagner, Alexandra; Fontaine, Coralie; Lenfant, Françoise; Arnal, Jean-François; Gourdy, Pierre

    2017-01-01

    Estrogen receptor alpha (ERα) has been demonstrated to play a key role in reproduction but also to exert numerous functions in nonreproductive tissues. Accordingly, ERα is now recognized as a key regulator of energy homeostasis and glucose metabolism and mediates the protective effects of estrogens against obesity and type 2 diabetes. This chapter attempts to summarize our current understanding of the mechanisms of ERα activation and their involvement in the modulation of energy balance and glucose metabolism. We first focus on the experimental studies that constitute the basis of the understanding of ERα as a nuclear receptor and more specifically on the key roles played by its two activation functions (AFs). We depict the consequences of the selective inactivation of these AFs in mouse models, which further underline the prominent role of nuclear ERα in the prevention of obesity and diabetes, as on the reproductive tract and the vascular system. Besides these nuclear actions, a fraction of ERα is associated with the plasma membrane and activates nonnuclear signaling from this site. Such rapid effects, called membrane-initiated steroid signals (MISS), have been characterized in a variety of cell lines and in particular in endothelial cells. The development of selective pharmacological tools that specifically activate MISS as well as the generation of mice expressing an ERα protein impeded for membrane localization has just begun to unravel the physiological role of MISS in vivo and their contribution to ERα-mediated metabolic protection. Finally, we discuss novel perspectives for the design of tissue-selective ER modulators.

  15. The cannabinoid CB1 receptor and mTORC1 signalling pathways interact to modulate glucose homeostasis in mice

    Directory of Open Access Journals (Sweden)

    Francisco J. Bermudez-Silva

    2016-01-01

    Full Text Available The endocannabinoid system (ECS is an intercellular signalling mechanism that is present in the islets of Langerhans and plays a role in the modulation of insulin secretion and expansion of the β-cell mass. The downstream signalling pathways mediating these effects are poorly understood. Mammalian target of rapamycin complex 1 (mTORC1 signalling is a key intracellular pathway involved in energy homeostasis and is known to importantly affect the physiology of pancreatic islets. We investigated the possible relationship between cannabinoid type 1 (CB1 receptor signalling and the mTORC1 pathway in the endocrine pancreas of mice by using pharmacological analysis as well as mice genetically lacking the CB1 receptor or the downstream target of mTORC1, the kinase p70S6K1. In vitro static secretion experiments on islets, western blotting, and in vivo glucose and insulin tolerance tests were performed. The CB1 receptor antagonist rimonabant decreased glucose-stimulated insulin secretion (GSIS at 0.1 µM while increasing phosphorylation of p70S6K1 and ribosomal protein S6 (rpS6 within the islets. Specific pharmacological blockade of mTORC1 by 3 nM rapamycin, as well as genetic deletion of p70S6K1, impaired the CB1-antagonist-mediated decrease in GSIS. In vivo experiments showed that 3 mg/kg body weight rimonabant decreased insulin levels and induced glucose intolerance in lean mice without altering peripheral insulin sensitivity; this effect was prevented by peripheral administration of low doses of rapamycin (0.1 mg/kg body weight, which increased insulin sensitivity. These findings suggest a functional interaction between the ECS and the mTORC1 pathway within the endocrine pancreas and at the whole-organism level, which could have implications for the development of new therapeutic approaches for pancreatic β-cell diseases.

  16. Planar Cell Polarity Controls Pancreatic Beta Cell Differentiation and Glucose Homeostasis

    DEFF Research Database (Denmark)

    Cortijo, Cedric; Gouzi, Mathieu; Tissir, Fadel

    2012-01-01

    glucose clearance. Loss of Celsr2 and 3 leads to a reduction of Jun phosphorylation in progenitors, which, in turn, reduces beta cell differentiation from endocrine progenitors. These results highlight the importance of the PCP pathway in cell differentiation in vertebrates. In addition, they reveal.......5 synchronously to apicobasal polarization of pancreas progenitors. Loss of function of the two PCP core components Celsr2 and Celsr3 shows that they control the differentiation of endocrine cells from polarized progenitors, with a prevalent effect on insulin-producing beta cells. This results in a decreased...

  17. Effect of high-dose pitavastatin on glucose homeostasis in patients at elevated risk of new-onset diabetes: insights from the CAPITAIN and PREVAIL-US studies.

    Science.gov (United States)

    Chapman, M J; Orsoni, A; Robillard, P; Hounslow, N; Sponseller, C A; Giral, P

    2014-05-01

    Statin treatment may impair glucose homeostasis and increase the risk of new-onset diabetes mellitus, although this may depend on the statin, dose and patient population. We evaluated the effects of pitavastatin 4 mg/day on glucose homeostasis in patients with metabolic syndrome in the CAPITAIN trial. Findings were validated in a subset of patients enrolled in PREVAIL-US. Participants with a well defined metabolic syndrome phenotype were recruited to CAPITAIN to reduce the influence of confounding factors. Validation and comparison datasets were selected comprising phenotypically similar subsets of individuals enrolled in PREVAIL-US and treated with pitavastatin or pravastatin, respectively. Mean change from baseline in parameters of glucose homeostasis (fasting plasma glucose [FPG], glycated hemoglobin [HbA1c], insulin, quantitative insulin-sensitivity check index [QUICKI] and homeostasis model of assessment-insulin resistance [HOMA-IR]) and plasma lipid profile were assessed at 6 months (CAPITAIN) and 3 months (PREVAIL-US) after initiating treatment. In CAPITAIN (n = 12), no significant differences from baseline in HbA1c, insulin, HOMA-IR and QUICKI were observed at day 180 in patients treated with pitavastatin. A small (4%) increase in FPG from baseline to day 180 (P  0.05). Similar results were observed for pravastatin in the comparison dataset (n = 14). Other than a small change in FPG in the CAPITAIN study, neutral effects of pitavastatin on glucose homeostasis were observed in two cohorts of patients with metabolic syndrome, independent of its efficacy in reducing levels of atherogenic lipoproteins. The small number of patients and relatively short follow-up period represent limitations of the study. Nevertheless, these data suggest that statin-induced diabetogenesis may not represent a class effect.

  18. Lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis in the adult central nervous system.

    Science.gov (United States)

    Liu, Qiang; Zhang, Juan; Zerbinatti, Celina; Zhan, Yan; Kolber, Benedict J; Herz, Joachim; Muglia, Louis J; Bu, Guojun

    2011-01-11

    Obesity is a growing epidemic characterized by excess fat storage in adipocytes. Although lipoprotein receptors play important roles in lipid uptake, their role in controlling food intake and obesity is not known. Here we show that the lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis. Conditional deletion of the Lrp1 gene in the brain resulted in an obese phenotype characterized by increased food intake, decreased energy consumption, and decreased leptin signaling. LRP1 directly binds to leptin and the leptin receptor complex and is required for leptin receptor phosphorylation and Stat3 activation. We further showed that deletion of the Lrp1 gene specifically in the hypothalamus by Cre lentivirus injection is sufficient to trigger accelerated weight gain. Together, our results demonstrate that the lipoprotein receptor LRP1, which is critical in lipid metabolism, also regulates food intake and energy homeostasis in the adult central nervous system.

  19. Lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis in the adult central nervous system.

    Directory of Open Access Journals (Sweden)

    Qiang Liu

    2011-01-01

    Full Text Available Obesity is a growing epidemic characterized by excess fat storage in adipocytes. Although lipoprotein receptors play important roles in lipid uptake, their role in controlling food intake and obesity is not known. Here we show that the lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis. Conditional deletion of the Lrp1 gene in the brain resulted in an obese phenotype characterized by increased food intake, decreased energy consumption, and decreased leptin signaling. LRP1 directly binds to leptin and the leptin receptor complex and is required for leptin receptor phosphorylation and Stat3 activation. We further showed that deletion of the Lrp1 gene specifically in the hypothalamus by Cre lentivirus injection is sufficient to trigger accelerated weight gain. Together, our results demonstrate that the lipoprotein receptor LRP1, which is critical in lipid metabolism, also regulates food intake and energy homeostasis in the adult central nervous system.

  20. Role of myotonic dystrophy protein kinase (DMPK in glucose homeostasis and muscle insulin action.

    Directory of Open Access Journals (Sweden)

    Esther Llagostera

    2007-11-01

    Full Text Available Myotonic dystrophy 1 (DM1 is caused by a CTG expansion in the 3'-unstranslated region of the DMPK gene, which encodes a serine/threonine protein kinase. One of the common clinical features of DM1 patients is insulin resistance, which has been associated with a pathogenic effect of the repeat expansions. Here we show that DMPK itself is a positive modulator of insulin action. DMPK-deficient (dmpk-/- mice exhibit impaired insulin signaling in muscle tissues but not in adipocytes and liver, tissues in which DMPK is not expressed. Dmpk-/- mice display metabolic derangements such as abnormal glucose tolerance, reduced glucose uptake and impaired insulin-dependent GLUT4 trafficking in muscle. Using DMPK mutants, we show that DMPK is required for a correct intracellular trafficking of insulin and IGF-1 receptors, providing a mechanism to explain the molecular and metabolic phenotype of dmpk-/- mice. Taken together, these findings indicate that reduced DMPK expression may directly influence the onset of insulin-resistance in DM1 patients and point to dmpk as a new candidate gene for susceptibility to type 2-diabetes.

  1. Diglycosyl diselenides alter redox homeostasis and glucose consumption of infective African trypanosomes

    Directory of Open Access Journals (Sweden)

    Jaime Franco

    2017-12-01

    Full Text Available With the aim to develop compounds able to target multiple metabolic pathways and, thus, to lower the chances of drug resistance, we investigated the anti-trypanosomal activity and selectivity of a series of symmetric diglycosyl diselenides and disulfides. Of 18 compounds tested the fully acetylated forms of di-β-D-glucopyranosyl and di-β-D-galactopyranosyl diselenides (13 and 15, respectively displayed strong growth inhibition against the bloodstream stage of African trypanosomes (EC50 0.54 μM for 13 and 1.49 μM for 15 although with rather low selectivity (SI < 10 assayed with murine macrophages. Nonacetylated versions of the same sugar diselenides proved to be, however, much less efficient or completely inactive to suppress trypanosome growth. Significantly, the galactosyl (15, and to a minor extent the glucosyl (13, derivative inhibited glucose catabolism but not its uptake. Both compounds induced redox unbalance in the pathogen. In vitro NMR analysis indicated that diglycosyl diselenides react with glutathione, under physiological conditions, via formation of selenenylsulfide bonds. Our results suggest that non-specific cellular targets as well as actors of the glucose and the redox metabolism of the parasite may be affected. These molecules are therefore promising leads for the development of novel multitarget antitrypanosomal agents. Keywords: Glutathione, Redox biosensor, Selenosugar, Trypanosome inhibition, Selenium NMR

  2. The optimal blood glucose level for critically ill adult patients.

    Science.gov (United States)

    Lv, Shaoning; Ross, Paul; Tori, Kathleen

    2017-09-01

    Glycaemic control is recognized as one of the important aspects in managing critically ill patients. Both hyperglycaemia and hypoglycaemia independently increase the risk of patient mortality. Hence, the identification of optimal glycaemic control is of paramount importance in the management of critically ill patients. The aim of this literature review is to examine the current status of glycaemic control in critically ill adult patients. This literature review will focus on randomized controlled trials comparing intensive insulin therapy to conventional insulin therapy, with an objective to identify optimal blood glucose level targets for critically ill adult patients. A literature review was conducted to identify large randomized controlled trials for the optimal targeted blood glucose level for critically ill adult patients published since 2000. A total of eight studies fulfilled the selection criteria of this review. With current human and technology resources, the results of the studies support commencing glycaemic control once the blood glucose level of critically ill patients reaches 10 mmol/L and maintaining this level between 8 mmol/L and 10 mmol/L. This literature review provides a recommendation for targeting the optimal blood glucose level for critically ill patients within moderate blood glucose level target range (8-10 mmol/L). The need for uniformed glucometrics for unbiased reporting and further research for optimal blood glucose target is required, especially in light of new technological advancements in closed-loop insulin delivery and monitoring devices. This literature review has revealed a need to call for consensus in the measurement and reporting of glycaemic control using standardized glucometrics. © 2017 British Association of Critical Care Nurses.

  3. Requirement of matrix metalloproteinase-1 for intestinal homeostasis in the adult Drosophila midgut

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Shin-Hae; Park, Joung-Sun [Department of Molecular Biology, College of Natural Science, Pusan National University, Busan 609-735 (Korea, Republic of); Kim, Young-Shin [Research Institute of Genetic Engineering, Pusan National University, Busan 609-735 (Korea, Republic of); Chung, Hae-Young [Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan 609-735 (Korea, Republic of); Yoo, Mi-Ae, E-mail: mayoo@pusan.ac.kr [Department of Molecular Biology, College of Natural Science, Pusan National University, Busan 609-735 (Korea, Republic of)

    2012-03-10

    Stem cells are tightly regulated by both intrinsic and extrinsic signals as well as the extracellular matrix (ECM) for tissue homeostasis and regenerative capacity. Matrix metalloproteinases (MMPs), proteolytic enzymes, modulate the turnover of numerous substrates, including cytokine precursors, growth factors, and ECM molecules. However, the roles of MMPs in the regulation of adult stem cells are poorly understood. In the present study, we utilize the Drosophila midgut, which is an excellent model system for studying stem cell biology, to show that Mmp1 is involved in the regulation of intestinal stem cells (ISCs). The results showed that Mmp1 is expressed in the adult midgut and that its expression increases with age and with exposure to oxidative stress. Mmp1 knockdown or Timp-overexpressing flies and flies heterozygous for a viable, hypomorphic Mmp1 allele increased ISC proliferation in the gut, as shown by staining with an anti-phospho-histone H3 antibody and BrdU incorporation assays. Reduced Mmp1 levels induced intestinal hyperplasia, and the Mmp1depletion-induced ISC proliferation was rescued by the suppression of the EGFR signaling pathway, suggesting that Mmp1 regulates ISC proliferation through the EGFR signaling pathway. Furthermore, adult gut-specific knockdown and whole-animal heterozygotes of Mmp1 increased additively sensitivity to paraquat-induced oxidative stress and shortened lifespan. Our data suggest that Drosophila Mmp1 is involved in the regulation of ISC proliferation for maintenance of gut homeostasis. -- Highlights: Black-Right-Pointing-Pointer Mmp1 is expressed in the adult midgut. Black-Right-Pointing-Pointer Mmp1 is involved in the regulation of ISC proliferation activity. Black-Right-Pointing-Pointer Mmp1-related ISC proliferation is associated with EGFR signaling. Black-Right-Pointing-Pointer Mmp1 in the gut is required for the intestinal homeostasis and longevity.

  4. Requirement of matrix metalloproteinase-1 for intestinal homeostasis in the adult Drosophila midgut

    International Nuclear Information System (INIS)

    Lee, Shin-Hae; Park, Joung-Sun; Kim, Young-Shin; Chung, Hae-Young; Yoo, Mi-Ae

    2012-01-01

    Stem cells are tightly regulated by both intrinsic and extrinsic signals as well as the extracellular matrix (ECM) for tissue homeostasis and regenerative capacity. Matrix metalloproteinases (MMPs), proteolytic enzymes, modulate the turnover of numerous substrates, including cytokine precursors, growth factors, and ECM molecules. However, the roles of MMPs in the regulation of adult stem cells are poorly understood. In the present study, we utilize the Drosophila midgut, which is an excellent model system for studying stem cell biology, to show that Mmp1 is involved in the regulation of intestinal stem cells (ISCs). The results showed that Mmp1 is expressed in the adult midgut and that its expression increases with age and with exposure to oxidative stress. Mmp1 knockdown or Timp-overexpressing flies and flies heterozygous for a viable, hypomorphic Mmp1 allele increased ISC proliferation in the gut, as shown by staining with an anti-phospho-histone H3 antibody and BrdU incorporation assays. Reduced Mmp1 levels induced intestinal hyperplasia, and the Mmp1depletion-induced ISC proliferation was rescued by the suppression of the EGFR signaling pathway, suggesting that Mmp1 regulates ISC proliferation through the EGFR signaling pathway. Furthermore, adult gut-specific knockdown and whole-animal heterozygotes of Mmp1 increased additively sensitivity to paraquat-induced oxidative stress and shortened lifespan. Our data suggest that Drosophila Mmp1 is involved in the regulation of ISC proliferation for maintenance of gut homeostasis. -- Highlights: ► Mmp1 is expressed in the adult midgut. ► Mmp1 is involved in the regulation of ISC proliferation activity. ► Mmp1-related ISC proliferation is associated with EGFR signaling. ► Mmp1 in the gut is required for the intestinal homeostasis and longevity.

  5. A dual role of lipasin (betatrophin) in lipid metabolism and glucose homeostasis: consensus and controversy.

    Science.gov (United States)

    Zhang, Ren; Abou-Samra, Abdul B

    2014-09-13

    Metabolic syndrome includes glucose intolerance and dyslipidemia, both of which are strong risk factors for developing diabetes and atherosclerotic cardiovascular diseases. Recently, multiple groups independently studied a previously uncharacterized gene, officially named C19orf80 (human) and Gm6484 (mouse), but more commonly known as RIFL, Angptl8, betatrophin and lipasin. Both exciting and conflicting results have been obtained, and significant controversy is ongoing. Accumulating evidence from genome wide association studies and mouse genetic studies convincingly shows that lipasin is involved in lipid regulation. However, the mechanism of action, the identity of transcription factors mediating its nutritional regulation, circulating levels, and relationship among lipasin, Angptl3 and Angptl4, remain elusive. Betatrophin represents a promising drug target for replenishing β-cell mass, but current results have not been conclusive regarding its potency and specificity. Here, we summarize the consensus and controversy regarding functions of lipasin/betatrophin based on currently available evidence.

  6. A composite computational model of liver glucose homeostasis. I. Building the composite model.

    Science.gov (United States)

    Hetherington, J; Sumner, T; Seymour, R M; Li, L; Rey, M Varela; Yamaji, S; Saffrey, P; Margoninski, O; Bogle, I D L; Finkelstein, A; Warner, A

    2012-04-07

    A computational model of the glucagon/insulin-driven liver glucohomeostasis function, focusing on the buffering of glucose into glycogen, has been developed. The model exemplifies an 'engineering' approach to modelling in systems biology, and was produced by linking together seven component models of separate aspects of the physiology. The component models use a variety of modelling paradigms and degrees of simplification. Model parameters were determined by an iterative hybrid of fitting to high-scale physiological data, and determination from small-scale in vitro experiments or molecular biological techniques. The component models were not originally designed for inclusion within such a composite model, but were integrated, with modification, using our published modelling software and computational frameworks. This approach facilitates the development of large and complex composite models, although, inevitably, some compromises must be made when composing the individual models. Composite models of this form have not previously been demonstrated.

  7. Bisphenol A, phthalate metabolites and glucose homeostasis in healthy normal-weight children

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    Amalie Carlsson

    2018-01-01

    Full Text Available Introduction: Bisphenol A and several of the most commonly used phthalates have been associated with adverse metabolic health effects such as obesity and diabetes. Therefore, we analyzed these man-made chemicals in first morning urine samples from 107 healthy normal-weight Danish children and adolescents. Method: This was a cross-sectional study. Participants were recruited as part of the Copenhagen Puberty Study. The subjects were evaluated by an oral glucose tolerance test (OGTT, a dual-energy X-ray absorptiometry (DXA scan, direct oxygen uptake measurement during cycle ergometry and fasting blood samples. First morning urine was collected and phthalate metabolites and BPA were measured by liquid chromatography-tandem mass spectrometry (LC–MS/MS with prior enzymatic deconjugation. Individual chemical concentrations were divided into tertiles and analyzed in relation to biological outcome. Results: Children in the lowest tertile of urinary BPA had significantly higher peak insulin levels during OGTT (P = 0.01, lower insulin sensitivity index (P < 0.01, higher leptin (P = 0.03, triglyceride (P < 0.01 and total cholesterol levels (P = 0.04, lower aerobic fitness (P = 0.02 and a tendency toward higher fat mass index (P = 0.1 compared with children in the highest tertile for uBPA. No significant differences in anthropometrics, body composition or glucose metabolism were associated with any of the phthalate metabolites measured. Conclusion: This pilot study on healthy normal-weight children suggests an inverse association between BPA and insulin resistance. Our findings contrast other cross-sectional studies showing a positive association for BPA, which may be due to confounding or reverse causation because diet is an important source of both BPA exposure and obesity.

  8. Plasma metabolomic profiles reflective of glucose homeostasis in non-diabetic and type 2 diabetic obese African-American women.

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    Oliver Fiehn

    2010-12-01

    Full Text Available Insulin resistance progressing to type 2 diabetes mellitus (T2DM is marked by a broad perturbation of macronutrient intermediary metabolism. Understanding the biochemical networks that underlie metabolic homeostasis and how they associate with insulin action will help unravel diabetes etiology and should foster discovery of new biomarkers of disease risk and severity. We examined differences in plasma concentrations of >350 metabolites in fasted obese T2DM vs. obese non-diabetic African-American women, and utilized principal components analysis to identify 158 metabolite components that strongly correlated with fasting HbA1c over a broad range of the latter (r = -0.631; p<0.0001. In addition to many unidentified small molecules, specific metabolites that were increased significantly in T2DM subjects included certain amino acids and their derivatives (i.e., leucine, 2-ketoisocaproate, valine, cystine, histidine, 2-hydroxybutanoate, long-chain fatty acids, and carbohydrate derivatives. Leucine and valine concentrations rose with increasing HbA1c, and significantly correlated with plasma acetylcarnitine concentrations. It is hypothesized that this reflects a close link between abnormalities in glucose homeostasis, amino acid catabolism, and efficiency of fuel combustion in the tricarboxylic acid (TCA cycle. It is speculated that a mechanism for potential TCA cycle inefficiency concurrent with insulin resistance is "anaplerotic stress" emanating from reduced amino acid-derived carbon flux to TCA cycle intermediates, which if coupled to perturbation in cataplerosis would lead to net reduction in TCA cycle capacity relative to fuel delivery.

  9. Expression of peroxisome proliferator-activated receptor-gamma in key neuronal subsets regulating glucose metabolism and energy homeostasis.

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    Sarruf, David A; Yu, Fang; Nguyen, Hong T; Williams, Diana L; Printz, Richard L; Niswender, Kevin D; Schwartz, Michael W

    2009-02-01

    In addition to increasing insulin sensitivity and adipogenesis, peroxisome proliferator-activated receptor (PPAR)-gamma agonists cause weight gain and hyperphagia. Given the central role of the brain in the control of energy homeostasis, we sought to determine whether PPARgamma is expressed in key brain areas involved in metabolic regulation. Using immunohistochemistry, PPARgamma distribution and its colocalization with neuron-specific protein markers were investigated in rat and mouse brain sections spanning the hypothalamus, the ventral tegmental area, and the nucleus tractus solitarius. In several brain areas, nuclear PPARgamma immunoreactivity was detected in cells that costained for neuronal nuclei, a neuronal marker. In the hypothalamus, PPARgamma immunoreactivity was observed in a majority of neurons in the arcuate (including both agouti related protein and alpha-MSH containing cells) and ventromedial hypothalamic nuclei and was also present in the hypothalamic paraventricular nucleus, the lateral hypothalamic area, and tyrosine hydroxylase-containing neurons in the ventral tegmental area but was not expressed in the nucleus tractus solitarius. To validate and extend these histochemical findings, we generated mice with neuron-specific PPARgamma deletion using nestin cre-LoxP technology. Compared with littermate controls, neuron-specific PPARgamma knockout mice exhibited dramatic reductions of both hypothalamic PPARgamma mRNA levels and PPARgamma immunoreactivity but showed no differences in food intake or body weight over a 4-wk study period. We conclude that: 1) PPARgamma mRNA and protein are expressed in the hypothalamus, 2) neurons are the predominant source of PPARgamma in the central nervous system, although it is likely expressed by nonneuronal cell types as well, and 3) arcuate nucleus neurons that control energy homeostasis and glucose metabolism are among those in which PPARgamma is expressed.

  10. Rauwolfia serpentina improves altered glucose and lipid homeostasis in fructose-induced type 2 diabetic mice.

    Science.gov (United States)

    Azmi, Muhammad Bilal; Qureshi, Shamim A

    2016-09-01

    Rauwolfia serpentina is well-reported in traditional medicines for the treatment of hypertensive and neurological disorders. However, its antidiabetic potential has been currently described in both alloxan-treated and normoglycemic mice. Present effort was carried out to investigate the effect of methanol root extract (MREt) of R.serpentina in fructose-induced type 2 diabetic mice. Experimental mice were grouped into normal control (distilled water 1ml/kg) and fructose-induced type 2 diabetic groups (10% fructose 1 ml/kg).The second group sub-divided into negative (0.05% DMSO 1ml/kg) control, positive (pioglitazone 15mg/kg) control and three test groups (MREt 10, 30 & 60 mg/kg). Each treatment was given orally for 14 days consecutively then mice were sacrificed in order to collect serum and liver samples to analyze physical, biochemical as well as hematological markers. MREt significantly improved percent body weight and glycemic change along with serum insulin, total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL-c), very low-density lipoprotein (VLDL-c), high-density lipoprotein-cholesterols (HDL-c), total hemoglobin, glycosylated hemoglobin, hepatic glycogen, coronary risk and fasting insulin resistance indices while suppressed down the activity of 3-hydroxy-3-methylglutaryl Coenzyme A reductase enzyme in test groups when compared with diabetic controls. The present findings conclude that MREt of R. serpentina can effectively betters the carbohydrate and lipid homeostasis by either inhibiting fructose absorption in intestine or decreasing insulin resistance in fructose-induced type 2 diabetic mice.

  11. Brown and beige fat in humans: thermogenic adipocytes that control energy and glucose homeostasis.

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    Sidossis, Labros; Kajimura, Shingo

    2015-02-01

    Brown adipose tissue (BAT), a specialized fat that dissipates energy to produce heat, plays an important role in the regulation of energy balance. Two types of thermogenic adipocytes with distinct developmental and anatomical features exist in rodents and humans: classical brown adipocytes and beige (also referred to as brite) adipocytes. While classical brown adipocytes are located mainly in dedicated BAT depots of rodents and infants, beige adipocytes sporadically reside with white adipocytes and emerge in response to certain environmental cues, such as chronic cold exposure, a process often referred to as "browning" of white adipose tissue. Recent studies indicate the existence of beige adipocytes in adult humans, making this cell type an attractive therapeutic target for obesity and obesity-related diseases, including type 2 diabetes. This Review aims to cover recent progress in our understanding of the anatomical, developmental, and functional characteristics of brown and beige adipocytes and discuss emerging questions, with a special emphasis on adult human BAT.

  12. Smartphone-controlled optogenetically engineered cells enable semiautomatic glucose homeostasis in diabetic mice.

    Science.gov (United States)

    Shao, Jiawei; Xue, Shuai; Yu, Guiling; Yu, Yuanhuan; Yang, Xueping; Bai, Yu; Zhu, Sucheng; Yang, Linfeng; Yin, Jianli; Wang, Yidan; Liao, Shuyong; Guo, Sanwei; Xie, Mingqi; Fussenegger, Martin; Ye, Haifeng

    2017-04-26

    With the increasingly dominant role of smartphones in our lives, mobile health care systems integrating advanced point-of-care technologies to manage chronic diseases are gaining attention. Using a multidisciplinary design principle coupling electrical engineering, software development, and synthetic biology, we have engineered a technological infrastructure enabling the smartphone-assisted semiautomatic treatment of diabetes in mice. A custom-designed home server SmartController was programmed to process wireless signals, enabling a smartphone to regulate hormone production by optically engineered cells implanted in diabetic mice via a far-red light (FRL)-responsive optogenetic interface. To develop this wireless controller network, we designed and implanted hydrogel capsules carrying both engineered cells and wirelessly powered FRL LEDs (light-emitting diodes). In vivo production of a short variant of human glucagon-like peptide 1 (shGLP-1) or mouse insulin by the engineered cells in the hydrogel could be remotely controlled by smartphone programs or a custom-engineered Bluetooth-active glucometer in a semiautomatic, glucose-dependent manner. By combining electronic device-generated digital signals with optogenetically engineered cells, this study provides a step toward translating cell-based therapies into the clinic. Copyright © 2017, American Association for the Advancement of Science.

  13. Planar Cell Polarity Controls Pancreatic Beta Cell Differentiation and Glucose Homeostasis

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    Cedric Cortijo

    2012-12-01

    Full Text Available Planar cell polarity (PCP refers to the collective orientation of cells within the epithelial plane. We show that progenitor cells forming the ducts of the embryonic pancreas express PCP proteins and exhibit an active PCP pathway. Planar polarity proteins are acquired at embryonic day 11.5 synchronously to apicobasal polarization of pancreas progenitors. Loss of function of the two PCP core components Celsr2 and Celsr3 shows that they control the differentiation of endocrine cells from polarized progenitors, with a prevalent effect on insulin-producing beta cells. This results in a decreased glucose clearance. Loss of Celsr2 and 3 leads to a reduction of Jun phosphorylation in progenitors, which, in turn, reduces beta cell differentiation from endocrine progenitors. These results highlight the importance of the PCP pathway in cell differentiation in vertebrates. In addition, they reveal that tridimensional organization and collective communication of cells are needed in the pancreatic epithelium in order to generate appropriate numbers of endocrine cells.

  14. Mitochondrial Sirtuin 4 Resolves Immune Tolerance in Monocytes by Rebalancing Glycolysis and Glucose Oxidation Homeostasis

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    Jie Tao

    2018-03-01

    Full Text Available The goal of this investigation was to define the molecular mechanism underlying physiologic conversion of immune tolerance to resolution of the acute inflammatory response, which is unknown. An example of this knowledge gap and its clinical importance is the broad-based energy deficit and immunometabolic paralysis in blood monocytes from non-survivors of human and mouse sepsis that precludes sepsis resolution. This immunometabolic dysregulation is biomarked by ex vivo endotoxin tolerance to increased glycolysis and TNF-α expression. To investigate how tolerance switches to resolution, we adapted our previously documented models associated with acute inflammatory, immune, and metabolic reprogramming that induces endotoxin tolerance as a model of sepsis in human monocytes. We report here that mitochondrial sirtuin 4 (SIRT4 physiologically breaks tolerance and resolves acute inflammation in human monocytes by coordinately reprogramming of metabolism and bioenergetics. We find that increased SIRT4 mRNA and protein expression during immune tolerance counters the increase in pyruvate dehydrogenase kinase 1 (PDK1 and SIRT1 that promote tolerance by switching glucose-dependent support of immune resistance to fatty acid oxidation support of immune tolerance. By decreasing PDK1, pyruvate dehydrogenase complex reactivation rebalances mitochondrial respiration, and by decreasing SIRT1, SIRT4 represses fatty acid oxidation. The precise mechanism for the mitochondrial SIRT4 nuclear feedback is unclear. Our findings are consistent with a new concept in which mitochondrial SIRT4 directs the axis that controls anabolic and catabolic energy sources.

  15. Class IIa histone deacetylases are hormone-activated regulators of FOXO and mammalian glucose homeostasis.

    Science.gov (United States)

    Mihaylova, Maria M; Vasquez, Debbie S; Ravnskjaer, Kim; Denechaud, Pierre-Damien; Yu, Ruth T; Alvarez, Jacqueline G; Downes, Michael; Evans, Ronald M; Montminy, Marc; Shaw, Reuben J

    2011-05-13

    Class IIa histone deacetylases (HDACs) are signal-dependent modulators of transcription with established roles in muscle differentiation and neuronal survival. We show here that in liver, class IIa HDACs (HDAC4, 5, and 7) are phosphorylated and excluded from the nucleus by AMPK family kinases. In response to the fasting hormone glucagon, class IIa HDACs are rapidly dephosphorylated and translocated to the nucleus where they associate with the promoters of gluconeogenic enzymes such as G6Pase. In turn, HDAC4/5 recruit HDAC3, which results in the acute transcriptional induction of these genes via deacetylation and activation of FOXO family transcription factors. Loss of class IIa HDACs in murine liver results in inhibition of FOXO target genes and lowers blood glucose, resulting in increased glycogen storage. Finally, suppression of class IIa HDACs in mouse models of type 2 diabetes ameliorates hyperglycemia, suggesting that inhibitors of class I/II HDACs may be potential therapeutics for metabolic syndrome. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Xbp1s in Pomc neurons connects ER stress with energy balance and glucose homeostasis.

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    Williams, Kevin W; Liu, Tiemin; Kong, Xingxing; Fukuda, Makoto; Deng, Yingfeng; Berglund, Eric D; Deng, Zhuo; Gao, Yong; Liu, Tianya; Sohn, Jong-Woo; Jia, Lin; Fujikawa, Teppei; Kohno, Daisuke; Scott, Michael M; Lee, Syann; Lee, Charlotte E; Sun, Kai; Chang, Yongsheng; Scherer, Philipp E; Elmquist, Joel K

    2014-09-02

    The molecular mechanisms underlying neuronal leptin and insulin resistance in obesity and diabetes remain unclear. Here we show that induction of the unfolded protein response transcription factor spliced X-box binding protein 1 (Xbp1s) in pro-opiomelanocortin (Pomc) neurons alone is sufficient to protect against diet-induced obesity as well as improve leptin and insulin sensitivity, even in the presence of strong activators of ER stress. We also demonstrate that constitutive expression of Xbp1s in Pomc neurons contributes to improved hepatic insulin sensitivity and suppression of endogenous glucose production. Notably, elevated Xbp1s levels in Pomc neurons also resulted in activation of the Xbp1s axis in the liver via a cell-nonautonomous mechanism. Together our results identify critical molecular mechanisms linking ER stress in arcuate Pomc neurons to acute leptin and insulin resistance as well as liver metabolism in diet-induced obesity and diabetes. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Neuronal Rap1 Regulates Energy Balance, Glucose Homeostasis, and Leptin Actions.

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    Kaneko, Kentaro; Xu, Pingwen; Cordonier, Elizabeth L; Chen, Siyu S; Ng, Amy; Xu, Yong; Morozov, Alexei; Fukuda, Makoto

    2016-09-13

    The CNS contributes to obesity and metabolic disease; however, the underlying neurobiological pathways remain to be fully established. Here, we show that the small GTPase Rap1 is expressed in multiple hypothalamic nuclei that control whole-body metabolism and is activated in high-fat diet (HFD)-induced obesity. Genetic ablation of CNS Rap1 protects mice from dietary obesity, glucose imbalance, and insulin resistance in the periphery and from HFD-induced neuropathological changes in the hypothalamus, including diminished cellular leptin sensitivity and increased endoplasmic reticulum (ER) stress and inflammation. Furthermore, pharmacological inhibition of CNS Rap1 signaling normalizes hypothalamic ER stress and inflammation, improves cellular leptin sensitivity, and reduces body weight in mice with dietary obesity. We also demonstrate that Rap1 mediates leptin resistance via interplay with ER stress. Thus, neuronal Rap1 critically regulates leptin sensitivity and mediates HFD-induced obesity and hypothalamic pathology and may represent a potential therapeutic target for obesity treatment. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Neuronal Rap1 Regulates Energy Balance, Glucose Homeostasis, and Leptin Actions

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    Kentaro Kaneko

    2016-09-01

    Full Text Available The CNS contributes to obesity and metabolic disease; however, the underlying neurobiological pathways remain to be fully established. Here, we show that the small GTPase Rap1 is expressed in multiple hypothalamic nuclei that control whole-body metabolism and is activated in high-fat diet (HFD-induced obesity. Genetic ablation of CNS Rap1 protects mice from dietary obesity, glucose imbalance, and insulin resistance in the periphery and from HFD-induced neuropathological changes in the hypothalamus, including diminished cellular leptin sensitivity and increased endoplasmic reticulum (ER stress and inflammation. Furthermore, pharmacological inhibition of CNS Rap1 signaling normalizes hypothalamic ER stress and inflammation, improves cellular leptin sensitivity, and reduces body weight in mice with dietary obesity. We also demonstrate that Rap1 mediates leptin resistance via interplay with ER stress. Thus, neuronal Rap1 critically regulates leptin sensitivity and mediates HFD-induced obesity and hypothalamic pathology and may represent a potential therapeutic target for obesity treatment.

  19. Resequencing of IRS2 reveals rare variants for obesity but not fasting glucose homeostasis in Hispanic children.

    Science.gov (United States)

    Butte, Nancy F; Voruganti, V Saroja; Cole, Shelley A; Haack, Karin; Comuzzie, Anthony G; Muzny, Donna M; Wheeler, David A; Chang, Kyle; Hawes, Alicia; Gibbs, Richard A

    2011-09-22

    Our objective was to resequence insulin receptor substrate 2 (IRS2) to identify variants associated with obesity- and diabetes-related traits in Hispanic children. Exonic and intronic segments, 5' and 3' flanking regions of IRS2 (∼14.5 kb), were bidirectionally sequenced for single nucleotide polymorphism (SNP) discovery in 934 Hispanic children using 3730XL DNA Sequencers. Additionally, 15 SNPs derived from Illumina HumanOmni1-Quad BeadChips were analyzed. Measured genotype analysis tested associations between SNPs and obesity and diabetes-related traits. Bayesian quantitative trait nucleotide analysis was used to statistically infer the most likely functional polymorphisms. A total of 140 SNPs were identified with minor allele frequencies (MAF) ranging from 0.001 to 0.47. Forty-two of the 70 coding SNPs result in nonsynonymous amino acid substitutions relative to the consensus sequence; 28 SNPs were detected in the promoter, 12 in introns, 28 in the 3'-UTR, and 2 in the 5'-UTR. Two insertion/deletions (indels) were detected. Ten independent rare SNPs (MAF = 0.001-0.009) were associated with obesity-related traits (P = 0.01-0.00002). SNP 10510452_139 in the promoter region was shown to have a high posterior probability (P = 0.77-0.86) of influencing BMI, fat mass, and waist circumference in Hispanic children. SNP 10510452_139 contributed between 2 and 4% of the population variance in body weight and composition. None of the SNPs or indels were associated with diabetes-related traits or accounted for a previously identified quantitative trait locus on chromosome 13 for fasting serum glucose. Rare but not common IRS2 variants may play a role in the regulation of body weight but not an essential role in fasting glucose homeostasis in Hispanic children.

  20. The effects of abnormalities of glucose homeostasis on the expression and binding of muscarinic receptors in cerebral cortex of rats.

    Science.gov (United States)

    Sherin, Antony; Peeyush, Kumar T; Naijil, George; Nandhu, Mohan Sobhana; Jayanarayanan, Sadanandan; Jes, Paul; Paulose, Cheramadathikudiyil Skaria

    2011-01-25

    Glucose homeostasis in humans is an important factor for the functioning of nervous system. Both hypo and hyperglycemia contributes to neuronal functional deficit. In the present study, effect of insulin induced hypoglycemia and streptozotocin induced diabetes on muscarinic receptor binding, cholinergic enzymes; AChE, ChAT expression and GLUT3 in the cerebral cortex of experimental rats were analysed. Total muscarinic, muscarinic M(1) receptor showed a significant decrease and muscarinic M(3) receptor subtype showed a significant increased binding in the cerebral cortex of hypoglycemic rats compared to diabetic and control. Real-Time PCR analysis of muscarinic M(1), M(3) receptor subtypes confirmed the receptor binding studies. Immunohistochemistry of muscarinic M(1), M(3) receptors using specific antibodies were also carried out. AChE and GLUT3 expression up regulated and ChAT expression down regulated in hypoglycemic rats compared to diabetic and control rats. Our results showed that hypo/hyperglycemia caused impaired glucose transport in neuronal cells as shown by altered expression of GLUT3. Increased AChE and decreased ChAT expression is suggested to alter cortical acetylcholine metabolism in experimental rats along with altered muscarinic receptor binding in hypo/hyperglycemic rats, impair cholinergic transmission, which subsequently lead to cholinergic dysfunction thereby causing learning and memory deficits. We observed a prominent cholinergic functional disturbance in hypoglycemic condition than in hyperglycemia. Hypoglycemia exacerbated the neurochemical changes in cerebral cortex induced by hyperglycemia. These findings have implications for both therapy and identification of causes contributing to neuronal dysfunction in diabetes. Copyright © 2010 Elsevier B.V. All rights reserved.

  1. FGF21 maintains glucose homeostasis by mediating the cross talk between liver and brain during prolonged fasting.

    Science.gov (United States)

    Liang, Qingning; Zhong, Ling; Zhang, Jialiang; Wang, Yu; Bornstein, Stefan R; Triggle, Chris R; Ding, Hong; Lam, Karen S L; Xu, Aimin

    2014-12-01

    Hepatic gluconeogenesis is a main source of blood glucose during prolonged fasting and is orchestrated by endocrine and neural pathways. Here we show that the hepatocyte-secreted hormone fibroblast growth factor 21 (FGF21) induces fasting gluconeogenesis via the brain-liver axis. Prolonged fasting induces activation of the transcription factor peroxisome proliferator-activated receptor α (PPARα) in the liver and subsequent hepatic production of FGF21, which enters into the brain to activate the hypothalamic-pituitary-adrenal (HPA) axis for release of corticosterone, thereby stimulating hepatic gluconeogenesis. Fasted FGF21 knockout (KO) mice exhibit severe hypoglycemia and defective hepatic gluconeogenesis due to impaired activation of the HPA axis and blunted release of corticosterone, a phenotype similar to that observed in PPARα KO mice. By contrast, intracerebroventricular injection of FGF21 reverses fasting hypoglycemia and impairment in hepatic gluconeogenesis by restoring corticosterone production in both FGF21 KO and PPARα KO mice, whereas all these central effects of FGF21 were abrogated by blockage of hypothalamic FGF receptor-1. FGF21 acts directly on the hypothalamic neurons to activate the mitogen-activated protein kinase extracellular signal-related kinase 1/2 (ERK1/2), thereby stimulating the expression of corticotropin-releasing hormone by activation of the transcription factor cAMP response element binding protein. Therefore, FGF21 maintains glucose homeostasis during prolonged fasting by fine tuning the interorgan cross talk between liver and brain. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  2. Adipocyte-specific protein tyrosine phosphatase 1B deletion increases lipogenesis, adipocyte cell size and is a minor regulator of glucose homeostasis.

    Directory of Open Access Journals (Sweden)

    Carl Owen

    Full Text Available Protein tyrosine phosphatase 1B (PTP1B, a key negative regulator of leptin and insulin signaling, is positively correlated with adiposity and contributes to insulin resistance. Global PTP1B deletion improves diet-induced obesity and glucose homeostasis via enhanced leptin signaling in the brain and increased insulin signaling in liver and muscle. However, the role of PTP1B in adipocytes is unclear, with studies demonstrating beneficial, detrimental or no effect(s of adipose-PTP1B-deficiency on body mass and insulin resistance. To definitively establish the role of adipocyte-PTP1B in body mass regulation and glucose homeostasis, adipocyte-specific-PTP1B knockout mice (adip-crePTP1B(-/- were generated using the adiponectin-promoter to drive Cre-recombinase expression. Chow-fed adip-crePTP1B(-/- mice display enlarged adipocytes, despite having similar body weight/adiposity and glucose homeostasis compared to controls. High-fat diet (HFD-fed adip-crePTP1B(-/- mice display no differences in body weight/adiposity but exhibit larger adipocytes, increased circulating glucose and leptin levels, reduced leptin sensitivity and increased basal lipogenesis compared to controls. This is associated with decreased insulin receptor (IR and Akt/PKB phosphorylation, increased lipogenic gene expression and increased hypoxia-induced factor-1-alpha (Hif-1α expression. Adipocyte-specific PTP1B deletion does not beneficially manipulate signaling pathways regulating glucose homeostasis, lipid metabolism or adipokine secretion in adipocytes. Moreover, PTP1B does not appear to be the major negative regulator of the IR in adipocytes.

  3. Gallic Acid Ameliorated Impaired Glucose and Lipid Homeostasis in High Fat Diet-Induced NAFLD Mice

    Science.gov (United States)

    Chao, Jung; Huo, Teh-Ia; Cheng, Hao-Yuan; Tsai, Jen-Chieh; Liao, Jiunn-Wang; Lee, Meng-Shiou; Qin, Xue-Mei; Hsieh, Ming-Tsuen; Pao, Li-Heng; Peng, Wen-Huang

    2014-01-01

    Gallic acid (GA), a naturally abundant plant phenolic compound in vegetables and fruits, has been shown to have potent anti-oxidative and anti-obesity activity. However, the effects of GA on nonalcoholic fatty liver disease (NAFLD) are poorly understood. In this study, we investigated the beneficial effects of GA administration on nutritional hepatosteatosis model by a more “holistic view” approach, namely 1H NMR-based metabolomics, in order to prove efficacy and to obtain information that might lead to a better understanding of the mode of action of GA. Male C57BL/6 mice were placed for 16 weeks on either a normal chow diet, a high fat diet (HFD, 60%), or a high fat diet supplemented with GA (50 and 100 mg/kg/day, orally). Liver histopathology and serum biochemical examinations indicated that the daily administration of GA protects against hepatic steatosis, obesity, hypercholesterolemia, and insulin resistance among the HFD-induced NAFLD mice. In addition, partial least squares discriminant analysis scores plots demonstrated that the cluster of HFD fed mice is clearly separated from the normal group mice plots, indicating that the metabolic characteristics of these two groups are distinctively different. Specifically, the GA-treated mice are located closer to the normal group of mice, indicating that the HFD-induced disturbances to the metabolic profile were partially reversed by GA treatment. Our results show that the hepatoprotective effect of GA occurs in part through a reversing of the HFD caused disturbances to a range of metabolic pathways, including lipid metabolism, glucose metabolism (glycolysis and gluconeogenesis), amino acids metabolism, choline metabolism and gut-microbiota-associated metabolism. Taken together, this study suggested that a 1H NMR-based metabolomics approach is a useful platform for natural product functional evaluation. The selected metabolites are potentially useful as preventive action biomarkers and could also be used to help

  4. Carotid intima-medial thickness and glucose homeostasis in Indian obese children and adolescents

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    Aashima Dabas

    2017-01-01

    Full Text Available Objective: To evaluate for subclinical atherosclerosis and its risk factors in Indian obese children. Materials and Methods: A cross-sectional, case–control study was conducted to recruit 80 children aged 6–17 years with constitutional obesity as cases and 23 age- and gender-matched controls with normal body mass index (BMI. Anthropometric and clinical evaluation was followed by biochemical analysis and body fat estimation by dual-energy X-ray absorptiometry in cases. Similar evaluation was performed for controls except laboratory parameters. Carotid intima-media thickness (CIMT was measured with B-mode ultrasonography in both cases and controls to evaluate subclinical atherosclerosis. Results: The mean age of cases was 12.8 ± 3 years, with mean BMI of 29.2 ± 4.8 kg/m2. The mean CIMT was significantly higher in cases than controls (0.54 ± 0.13 vs. 0.42 ± 0.08; P < 0.001 across all ages. CIMT was significantly higher in participants who were hypertensive than nonhypertensive (0.6 ± 0.11 vs. 0.53 ± 0.11 mm; P = 0.04. CIMT showed a positive correlation with BMI (r = 0.23, P = 0.02, percentage body fat and fat mass index (r = 0.28 and 0.3 respectively; P < 0.001, but not with waist: hip ratio. CIMT showed significant positive correlation with blood glucose at 60 min (r = 0.22; P = 0.04, serum insulin at 60 min (r = 0.28; P = 0.01 while negative correlation with whole body insulin sensitivity (r = −0.27; P = 0.01. Conclusion: CIMT correlated significantly to blood pressure, insulin sensitivity, and body fat in Indian obese children.

  5. The effects of glucose ingestion and glucose regulation on memory performance in older adults with mild cognitive impairment.

    Science.gov (United States)

    Riby, L M; Marriott, A; Bullock, R; Hancock, J; Smallwood, J; McLaughlin, J

    2009-04-01

    Previous research investigating the impact of glucose ingestion and/or improvements in glucose regulation has found selective cognitive facilitation on episodic memory tasks in successful ageing and dementia. The present study aimed to extend this research to mild cognitive impairment (MCI). In a repeated-measures design, 24 older adults with and 24 older adults without MCI performed a battery of memory and attention tasks after 25 g of glucose or a sweetness matched placebo. In addition, to assess the impact of individual differences in glucose regulation, blood glucose measurements were taken throughout the testing session. Consistent with previous research, cognitive facilitation was observed for episodic memory tasks only in both successful ageing and MCI. Older adults with MCI had a similar glucose regulatory response as controls but their fasting levels were elevated. Notably, higher levels of blood glucose were associated with impaired memory performance in both the glucose and placebo conditions. Importantly, both blood glucose and memory performance indices were significant predictors of MCI status. The utility of glucose supplementation and the use of glucose regulation as a biological marker are discussed in relation to these data.

  6. Alpha2delta-1 in SF1+ Neurons of the Ventromedial Hypothalamus Is an Essential Regulator of Glucose and Lipid Homeostasis

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    Jennifer A. Felsted

    2017-12-01

    Full Text Available Summary: The central mechanisms controlling glucose and lipid homeostasis are inadequately understood. We show that α2δ-1 is an essential regulator of glucose and lipid balance, acting in steroidogenic factor-1 (SF1 neurons of the ventromedial hypothalamus (VMH. These effects are body weight independent and involve regulation of SF1+ neuronal activity and sympathetic output to metabolic tissues. Accordingly, mice with α2δ-1 deletion in SF1 neurons exhibit glucose intolerance, altered lipolysis, and decreased cholesterol content in adipose tissue despite normal energy balance regulation. Profound reductions in the firing rate of SF1 neurons, decreased sympathetic output, and elevated circulating levels of serotonin are associated with these alterations. Normal calcium currents but reduced excitatory postsynaptic currents in mutant SF1 neurons implicate α2δ-1 in the promotion of excitatory synaptogenesis separate from its canonical role as a calcium channel subunit. Collectively, these findings identify an essential mechanism that regulates VMH neuronal activity and glycemic and lipid control and may be a target for tackling metabolic disease. : Felsted et al. show a required role of the calcium channel subunit and thrombospondin receptor α2δ-1 in regulating glucose and lipid homeostasis in the ventromedial hypothalamus (VMH. These effects are caused by regulation of SF1+ neuronal activity in the VMH through non-canonical mechanisms and concomitant influences on sympathetic output. Keywords: diabetes, VMH, hypothalamus, glucose, norepinephrine, serotonin, excitability, lipid, SF1

  7. Zinc transporter ZIP14 functions in hepatic zinc, iron and glucose homeostasis during the innate immune response (endotoxemia.

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    Tolunay Beker Aydemir

    altered in the Zip14(-/- mice and their phenotype shows defects in glucose homeostasis.

  8. Skeletal muscle neuronal nitric oxide synthase micro protein is reduced in people with impaired glucose homeostasis and is not normalized by exercise training.

    Science.gov (United States)

    Bradley, Scott J; Kingwell, Bronwyn A; Canny, Benedict J; McConell, Glenn K

    2007-10-01

    Skeletal muscle inducible nitric oxide synthase (NOS) protein is greatly elevated in people with type 2 diabetes mellitus, whereas endothelial NOS is at normal levels. Diabetic rat studies suggest that skeletal muscle neuronal NOS (nNOS) micro protein expression may be reduced in human insulin resistance. The aim of this study was to determine whether skeletal muscle nNOSmicro protein expression is reduced in people with impaired glucose homeostasis and whether exercise training increases nNOSmicro protein expression in these individuals because exercise training increases skeletal muscle nNOSmicro protein in rats. Seven people with type 2 diabetes mellitus or prediabetes (impaired fasting glucose and/or impaired glucose tolerance) and 7 matched (sex, age, fitness, body mass index, blood pressure, lipid profile) healthy controls aged 36 to 60 years participated in this study. Vastus lateralis muscle biopsies for nNOSmicro protein determination were obtained, aerobic fitness was measured (peak pulmonary oxygen uptake [Vo(2) peak]), and glucose tolerance and insulin homeostasis were assessed before and after 1 and 4 weeks of cycling exercise training (60% Vo(2) peak, 50 minutes x 5 d wk(-1)). Skeletal muscle nNOSmicro protein was significantly lower (by 32%) in subjects with type 2 diabetes mellitus or prediabetes compared with that in controls before training (17.7 +/- 1.2 vs 26.2 +/- 3.4 arbitrary units, P glucose homeostasis have reduced skeletal muscle nNOSmicro protein content. However, because exercise training improves insulin sensitivity without influencing skeletal muscle nNOSmicro protein expression, it seems that changes in skeletal muscle nNOSmicro protein are not central to the control of insulin sensitivity in humans and therefore may be a consequence rather than a cause of diabetes.

  9. FGF21 is not required for glucose homeostasis, ketosis or tumour suppression associated with ketogenic diets in mice.

    Science.gov (United States)

    Stemmer, Kerstin; Zani, Fabio; Habegger, Kirk M; Neff, Christina; Kotzbeck, Petra; Bauer, Michaela; Yalamanchilli, Suma; Azad, Ali; Lehti, Maarit; Martins, Paulo J F; Müller, Timo D; Pfluger, Paul T; Seeley, Randy J

    2015-10-01

    Ketogenic diets (KDs) have increasingly gained attention as effective means for weight loss and potential adjunctive treatment of cancer. The metabolic benefits of KDs are regularly ascribed to enhanced hepatic secretion of fibroblast growth factor 21 (FGF21) and its systemic effects on fatty-acid oxidation, energy expenditure (EE) and body weight. Ambiguous data from Fgf21-knockout animal strains and low FGF21 concentrations reported in humans with ketosis have nevertheless cast doubt regarding the endogenous function of FGF21. We here aimed to elucidate the causal role of FGF21 in mediating the therapeutic benefits of KDs on metabolism and cancer. We established a dietary model of increased vs decreased FGF21 by feeding C57BL/6J mice with KDs, either depleted of protein or enriched with protein. We furthermore used wild-type and Fgf21-knockout mice that were subjected to the respective diets, and monitored energy and glucose homeostasis as well as tumour growth after transplantation of Lewis lung carcinoma cells. Hepatic and circulating, but not adipose tissue, FGF21 levels were profoundly increased by protein starvation, independent of the state of ketosis. We demonstrate that endogenous FGF21 is not essential for the maintenance of normoglycaemia upon protein and carbohydrate starvation and is therefore not needed for the effects of KDs on EE. Furthermore, the tumour-suppressing effects of KDs were independent of FGF21 and, rather, driven by concomitant protein and carbohydrate starvation. Our data indicate that the multiple systemic effects of KD exposure in mice, previously ascribed to increased FGF21 secretion, are rather a consequence of protein malnutrition.

  10. Fibroblast growth factor 21 is not required for glucose homeostasis, ketosis and tumour suppression associated to ketogenic diets in mice

    Science.gov (United States)

    Stemmer, Kerstin; Zani, Fabio; Habegger, Kirk M.; Neff, Christina; Kotzbeck, Petra; Bauer, Michaela; Yalamanchilli, Suma; Azad, Ali; Lehti, Maarit; Martins, Paulo J.F.; Müller, Timo D.; Pfluger, Paul T.; Seeley, Randy J.

    2016-01-01

    AIMS/HYPOTHESIS Ketogenic diets (KDs) increasingly gained attention as effective means for weight loss and potential adjunctive treatment of cancer. Metabolic benefits of KDs are regularly ascribed towards enhanced hepatic secretion of fibroblast growth factor (FGF) 21, and its systemic effects on fatty acid oxidation, energy expenditure and body weight. Ambiguous data from Fgf21 knockout strains and low FGF21 concentrations reported for humans in ketosis have nevertheless cast doubt regarding the endogenous function of FGF21. We here aimed to elucidate the causal role of FGF21 in mediating therapeutic benefits of KDs on metabolism and cancer. METHODS We established a dietary model of increased vs. decreased FGF21 by feeding C57BL/6J mice with KDs, either depleted or enriched with protein, respectively. We furthermore used wild type and Fgf21 knockout mice that were subjected to the respective diets, and monitored energy and glucose homeostasis as well as tumor growth after transplantation of Lewis-Lung-Carcinoma cells. RESULTS Hepatic and circulating but not adipose tissue FGF21 levels were profoundly increased by protein starvation and independent of the state of ketosis. We demonstrate that endogenous FGF21 is not essential for the maintenance of normoglycemia upon protein and carbohydrate starvation and is dispensable for the effects of KDs on energy expenditure. Furthermore, the tumor-suppressing effects of KDs were independent from FGF21, and rather driven by concomitant protein and carbohydrate starvation. CONCLUSION/INTERPRETATION Our data indicate that multiple systemic effects of KDs exposure in mice that were previously ascribed towards increased FGF21 secretion are rather a consequence of protein malnutrition. PMID:26099854

  11. Effects of taurine supplementation and swimming, associated or not, on obesity and glucose homeostasis in mice - 10.4025/actascihealthsci.v34ispec.10433

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    Sandra Lucinei Balbo

    2012-12-01

    Full Text Available Studies show that physical exercise (PE is associated with a reduced fat accumulation and increased insulin sensitivity, and taurine (TAU improves glucose homeostasis in lean rodents. The aim  in this work was evaluate the effects of supplementing TAU and practice of PE, associated or not, on obesity and glucose homeostasis on obese MSG-mice. Neonate male Swiss mice received injections of monosodium glutamate (MSG group or saline (CON group. From the 30th to the 90th day of life, one group of animals received TAU in drinking water (MSG TAU group, another was subjected to PE (MSG PE group and a third group underwent both procedures (MSG PE TAU group. Mice treated with MSG become obese, hypertriglyceridemic, glucose intolerant and insulin resistant. The supplementation with TAU and the PE, isolated or associated, reduced the triglycerides (38%, glucose intolerance (around 30% and KITT (79% in MSG-obese animals, but did not influence the accumulation of fat. Interestingly, the combination of both strategies significantly reduced the insulin resistance, compared to animals subjected to isolated strategies. In conclusion, the supplementation with TAU and PE, isolated or associated, did not influence the accumulation of fat in MSG-obese mice, however, reduce the triglycerides and insulin resistance.  

  12. Association between triglyceride glucose index and arterial stiffness in Korean adults.

    Science.gov (United States)

    Lee, Sang Bae; Ahn, Chul Woo; Lee, Byoung Kwon; Kang, Shinae; Nam, Ji Sun; You, Ji Hong; Kim, Min Jin; Kim, Min Kyung; Park, Jong Suk

    2018-03-21

    The triglyceride glucose (TyG) index has been suggested as a simple surrogate marker of insulin resistance. However, there are limited data regarding the association between the TyG index and arterial stiffness in adults. Therefore, we evaluated the relationship between the TyG index and arterial stiffness as measured based on brachial ankle pulse wave velocity (baPWV) in Korean adults. A total of 3587 subjects were enrolled in this study. Anthropometric and cardiovascular risk factors were measured. The TyG index was calculated as ln[fasting triglycerides(mg/dl) × fasting glucose(mg/dl)/2], and the insulin resistance index of homeostasis model assessment (HOMA-IR) was estimated. Arterial stiffness was determined by measuring baPWV. The subjects were stratified into four groups based on the TyG index. There were significant differences in cardiovascular parameters among the groups; the mean baPWV increased significantly with increasing TyG index. According to the logistic regression analysis after adjusting for multiple risk factors, the odds ratio (95% CI) for increased baPWV (> 75th percentile) for the highest and lowest quartiles of the TyG index was 2.92 (1.92-4.44) in men and 1.84 (1.15-2.96) in women, and the odds ratio for increased baPWV for the highest and lowest quartiles of the HOMA-IR was 1.80 (1.17-2.78) in men and 1.46 (1.06-2.47) in women, respectively. The TyG index is more independently associated with increased arterial stiffness than HOMA-IR in Korean adults.

  13. Relationship between the triglyceride glucose index and coronary artery calcification in Korean adults.

    Science.gov (United States)

    Kim, Min Kyung; Ahn, Chul Woo; Kang, Shinae; Nam, Ji Sun; Kim, Kyung Rae; Park, Jong Suk

    2017-08-23

    The triglyceride glucose (TyG) index has been considered a simple surrogate marker of insulin resistance. However, few studies have investigated the relationship between the TyG index and coronary artery calcification (CAC). Thus, we investigated the relationship between the TyG index and CAC in healthy Korean adults. In total, 4319 participants who underwent cardiac computed tomography (CT) in a health promotion center were enrolled. Anthropometric profiles and multiple cardiovascular risk factors were measured. The TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2], and the insulin resistance index of homeostasis model assessment (HOMA-IR) was estimated. The CAC was measured using multidetector CT, and CAC presence was defined as an Agatston score of >0. All subjects were stratified into four groups based on their TyG indices. Significant differences were observed in cardiovascular parameters among the groups, and the prevalence of CAC significantly increased with increasing TyG index. In the logistic regression analysis after adjustment for multiple risk factors, the odds ratio for the prevalence of CAC, when comparing the highest and lowest quartiles of the TyG index was 1.95 (95% CI 1.23-3.11; P for trend = 0.01); the odds ratio for the prevalence of CAC, when comparing the highest and lowest quartiles of HOMA-IR was 1.64 (95% CI 1.12-2.40; P for trend = 0.04). In the receiver operating characteristics analysis, the TyG index was superior to HOMA-IR in predicting CAC. The TyG index is more independently associated with the presence of coronary artery atherosclerosis than is HOMA-IR in healthy Korean adults.

  14. p53-upregulated-modulator-of-apoptosis (PUMA) deficiency affects food intake but does not impact on body weight or glucose homeostasis in diet-induced obesity.

    Science.gov (United States)

    Litwak, Sara A.; Loh, Kim; Stanley, William J.; Pappas, Evan G.; Wali, Jibran A.; Selck, Claudia; Strasser, Andreas; Thomas, Helen E.; Gurzov, Esteban N.

    2016-01-01

    BCL-2 proteins have been implicated in the control of glucose homeostasis and metabolism in different cell types. Thus, the aim of this study was to determine the role of the pro-apoptotic BH3-only protein, p53-upregulated-modulator-of-apoptosis (PUMA), in metabolic changes mediated by diet-induced obesity, using PUMA deficient mice. At 10 weeks of age, knockout and wild type mice either continued consuming a low fat chow diet (6% fat), or were fed with a high fat diet (23% fat) for 14–17 weeks. We measured body composition, glucose and insulin tolerance, insulin response in peripheral tissues, energy expenditure, oxygen consumption, and respiratory exchange ratio in vivo. All these parameters were indistinguishable between wild type and knockout mice on chow diet and were modified equally by diet-induced obesity. Interestingly, we observed decreased food intake and ambulatory capacity of PUMA knockout mice on high fat diet. This was associated with increased adipocyte size and fasted leptin concentration in the blood. Our findings suggest that although PUMA is dispensable for glucose homeostasis in lean and obese mice, it can affect leptin levels and food intake during obesity. PMID:27033313

  15. The Exercise-Induced Irisin Is Associated with Improved Levels of Glucose Homeostasis Markers in Pregnant Women Participating in 8-Week Prenatal Group Fitness Program: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Anna Szumilewicz

    2017-01-01

    Full Text Available Background. Both exercise and pregnancy influence serum irisin concentration. Aim. To determine how the interaction of pregnancy and exercise affects irisin level and whether various patterns of exercise adherence had different effect on irisin concentration. Methods. It was a one-group pretest-posttest study among 9 Caucasian nulliparous healthy women in normal pregnancy (age 23±3 years, 21±2 weeks of gestation; mean ± SD who participated in 8-week group fitness program. Before and after exercise intervention, we determined serum concentrations of irisin and selected parameters of lipid profile and glucose homeostasis markers. Results. In active women, irisin slightly decreased with the development of pregnancy. After 8 weeks of exercising, irisin correlated negatively with fasting glucose (R = −0.922; p=0.001, glycated hemoglobin (R = −0.784; p=0.012, and insulin concentrations (R = −0.845; p=0.004. In women exercising below recommended level, we observed a significant drop in irisin concentration, whereas in women exercising at least three times a week this myokine slightly increased (31% difference; 90% confidence limits ±28; a large, clear effect. Conclusions. Irisin stimulated by prenatal exercise may improve glucose homeostasis markers in healthy women and compensate for metabolic changes induced by pregnancy. Moreover, the frequency of exercise may regulate the changes in exercise-induced irisin concentration.

  16. Brain-derived neurotrophic factor in the nucleus tractus solitarii modulates glucose homeostasis after carotid chemoreceptor stimulation in rats.

    Science.gov (United States)

    Montero, Sergio; Cuéllar, Ricardo; Lemus, Mónica; Avalos, Reyes; Ramírez, Gladys; de Álvarez-Buylla, Elena Roces

    2012-01-01

    Neuronal systems, which regulate energy intake, energy expenditure and endogenous glucose production, sense and respond to input from hormonal related signals that convey information from body energy availability. Carotid chemoreceptors (CChr) function as sensors for circulating glucose levels and contribute to glycemic counterregulatory responses. Brain-derived neurotrophic factor (BDNF) that plays an important role in the endocrine system to regulate glucose metabolism could play a role in hyperglycemic glucose reflex with brain glucose retention (BGR) evoked by anoxic CChr stimulation. Infusing BDNF into the nucleus tractus solitarii (NTS) before CChr stimulation, showed that this neurotrophin increased arterial glucose and BGR. In contrast, BDNF receptor (TrkB) antagonist (K252a) infusions in NTS resulted in a decrease in both glucose variables.

  17. Consumption of added sugars from liquid but not solid sources predicts impaired glucose homeostasis and insulin resistance among youth at risk of obesity.

    Science.gov (United States)

    Wang, Jiawei; Light, Kelly; Henderson, Mélanie; O'Loughlin, Jennifer; Mathieu, Marie-Eve; Paradis, Gilles; Gray-Donald, Katherine

    2014-01-01

    Little is known about longitudinal associations between added sugar consumption (solid and liquid sources) and glucose-insulin homeostasis among youth. Caucasian children (8-10 y) with at least one obese biological parent were recruited in the QUébec Adipose and Lifestyle InvesTigation in Youth (QUALITY) cohort (n = 630) and followed-up 2 y later (n = 564). Added sugars were assessed by 3 24-h dietary recalls at baseline. Two-year changes were examined in multivariate linear regression models, adjusting for baseline level, age, sex, Tanner stage, energy intake, fat mass (dual-energy X-ray absorptiometry), and physical activity (7 d accelerometer). Added sugar intake in either liquid or solid sources was not related to changes in adiposity measures (fat mass, body mass index, or waist circumference). However, a higher consumption (10 g/d) of added sugars from liquid sources was associated with 0.04 mmol/L higher fasting glucose, 2.3 pmol/L higher fasting insulin, 0.1 unit higher homeostasis model assessment of insulin resistance (HOMA-IR), and 0.4 unit lower Matsuda-insulin sensitivity index (Matsuda-ISI) in all participants (P added sugars from solid sources. Overweight/obese children at baseline had greater increases in adiposity indicators, fasting insulin, and HOMA-IR and decreases in Matsuda-ISI during those 2 y than normal-weight children. Consumption of added sugars from liquid or solid sources was not associated with changes in adiposity, but liquid added sugars were a risk factor for the development of impaired glucose homeostasis and insulin resistance over 2 y among youth at risk of obesity.

  18. Dietary glucose regulates yeast consumption in adult Drosophila males

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    Sebastien eLebreton

    2014-12-01

    Full Text Available The adjustment of feeding behavior in response to hunger and satiety contributes to homeostatic regulation in animals. The fruit fly Drosophila melanogaster feeds on yeasts growing on overripe fruit, providing nutrients required for adult survival, reproduction and larval growth. Here, we present data on how the nutritional value of food affects subsequent yeast consumption in Drosophila adult males. After a period of starvation, flies showed intensive yeast consumption. In comparison, flies stopped feeding after having access to a nutritive cornmeal diet. Interestingly, dietary glucose was equally efficient as the complex cornmeal diet. In contrast, flies fed with sucralose, a non-metabolizable sweetener, behaved as if they were starved. The adipokinetic hormone and insulin-like peptides regulate metabolic processes in insects. We did not find any effect of the adipokinetic hormone pathway on this modulation. Instead, the insulin pathway was involved in these changes. Flies lacking the insulin receptor did not respond to nutrient deprivation by increasing yeast consumption. Together these results show the importance of insulin in the regulation of yeast consumption in response to starvation in adult D. melanogaster males.

  19. Dietary glucose regulates yeast consumption in adult Drosophila males.

    Science.gov (United States)

    Lebreton, Sébastien; Witzgall, Peter; Olsson, Marie; Becher, Paul G

    2014-01-01

    The adjustment of feeding behavior in response to hunger and satiety contributes to homeostatic regulation in animals. The fruit fly Drosophila melanogaster feeds on yeasts growing on overripe fruit, providing nutrients required for adult survival, reproduction and larval growth. Here, we present data on how the nutritional value of food affects subsequent yeast consumption in Drosophila adult males. After a period of starvation, flies showed intensive yeast consumption. In comparison, flies stopped feeding after having access to a nutritive cornmeal diet. Interestingly, dietary glucose was equally efficient as the complex cornmeal diet. In contrast, flies fed with sucralose, a non-metabolizable sweetener, behaved as if they were starved. The adipokinetic hormone and insulin-like peptides regulate metabolic processes in insects. We did not find any effect of the adipokinetic hormone pathway on this modulation. Instead, the insulin pathway was involved in these changes. Flies lacking the insulin receptor (InR) did not respond to nutrient deprivation by increasing yeast consumption. Together these results show the importance of insulin in the regulation of yeast consumption in response to starvation in adult D. melanogaster males.

  20. Lifestyle, glucose regulation and the cognitive effects of glucose load in middle-aged adults

    OpenAIRE

    Riby, Leigh; McLaughlin, Jennifer; Riby, Deborah

    2008-01-01

    Interventions aimed at improving glucose regulatory mechanisms have been suggested as a possible source of cognitive enhancement in the elderly. In particular, previous research has identified episodic memory as a target for facilitation after either moderate increases in glycaemia (after a glucose drink) or after improvements in glucose regulation. The present study aimed to extend this research by examining the joint effects of glucose ingestion and glucose regulation on cognition. In addit...

  1. Dietary incorporation of whey proteins and galactooligosaccharides exhibits improvement in glucose homeostasis and insulin resistance in high fat diet fed mice

    Directory of Open Access Journals (Sweden)

    Praveen Kumar Kavadi

    2017-09-01

    Full Text Available Background: The present study was planned to investigate the effectiveness of whey protein isolate (WPI of high purity and a galactooligosaccharides (GOS preparation on glucose homeostasis and insulin resistance under high fat diet (45.47% energy from fat fed conditions in C57BL/6 mice. The mRNA expression of genes related to gluconeogenesis was also examined. Methods: Fasting blood glucose level, serum insulin & GLP-1 (ELISA were measured; HOMA-IR determined in different treatment groups. mRNA expression of gluconeogenesis genes in liver and small intestine tissues analysed by qRT-PCR. Results: Dietary incorporation of WPI/GOS alone or in combination was observed to significantly resist (p [J Complement Med Res 2017; 6(3.000: 326-332

  2. Dietary Fatty Acids Differentially Associate with Fasting Versus 2-Hour Glucose Homeostasis: Implications for The Management of Subtypes of Prediabetes

    Science.gov (United States)

    Guess, Nicola; Perreault, Leigh; Kerege, Anna; Strauss, Allison; Bergman, Bryan C.

    2016-01-01

    Over-nutrition has fuelled the global epidemic of type 2 diabetes, but the role of individual macronutrients to the diabetogenic process is not well delineated. We aimed to examine the impact of dietary fatty acid intake on fasting and 2-hour plasma glucose concentrations, as well as tissue-specific insulin action governing each. Normoglycemic controls (n = 15), athletes (n = 14), and obese (n = 23), as well as people with prediabetes (n = 10) and type 2 diabetes (n = 11), were queried about their habitual diet using a Food Frequency Questionnaire. All subjects were screened by an oral glucose tolerance test (OGTT) and studied using the hyperinsulinemic/euglycemic clamp with infusion of 6,62H2-glucose. Multiple regression was performed to examine relationships between dietary fat intake and 1) fasting plasma glucose, 2) % suppression of endogenous glucose production, 3) 2-hour post-OGTT plasma glucose, and 4) skeletal muscle insulin sensitivity (glucose rate of disappearance (Rd) and non-oxidative glucose disposal (NOGD)). The %kcal from saturated fat (SFA) was positively associated with fasting (β = 0.303, P = 0.018) and 2-hour plasma glucose (β = 0.415, Pprediabetic state. PMID:26999667

  3. [Influence of hormonal contraceptives on indices of zinc homeostasis and bone remodeling in young adult women].

    Science.gov (United States)

    Simões, Tania Mara Rodrigues; Zapata, Carmiña Lucía Vargas; Donangelo, Carmen Marino

    2015-09-01

    To investigate the influence of the use of oral hormonal contraceptive agents (OCA) on the biochemical indices related to metabolic zinc utilization and distribution, and to bone turnover in young adult women. Cross-sectional study. Blood and urine samples from non-users (-OCA; control; n=69) and users of hormonal contraceptives for at least 3 months (+OCA; n=62) were collected under controlled conditions. Indices of zinc homeostasis and of bone turnover were analyzed in serum or plasma (total, albumin-bound and α2-macroglobulin-bound zinc, albumin and total and bone alkaline phosphatase activity), in erythrocytes (zinc and metallothionein) and in urine (zinc, calcium and hydroxyproline). The habitual zinc and calcium intakes were evaluated by a food frequency questionnaire. Dietary zinc intake was similar in both groups and on average above recommended values, whereas calcium intake was similarly sub-adequate in +OCA and -OCA. Compared to controls, +OCA had lower concentrations of total and α2-macroglobulin-bound zinc (11 and 28.5%, respectively, puse decreases serum zinc, alters zinc distribution in major serum fractions with possible effects on tissue uptake, enhances zinc retention in the body and decreases bone turnover. Prolonged OCA use may lead to lower peak bone mass and/or to impaired bone mass maintenance in young women, particularly in those with marginal calcium intake. The observed OCA effects were more evident in women younger than 25 years and in nulliparous women, deserving special attention in future studies.

  4. The Thoc1 encoded ribonucleoprotein is required for myeloid progenitor cell homeostasis in the adult mouse.

    Science.gov (United States)

    Pitzonka, Laura; Ullas, Sumana; Chinnam, Meenalakshmi; Povinelli, Benjamin J; Fisher, Daniel T; Golding, Michelle; Appenheimer, Michelle M; Nemeth, Michael J; Evans, Sharon; Goodrich, David W

    2014-01-01

    Co-transcriptionally assembled ribonucleoprotein (RNP) complexes are critical for RNA processing and nuclear export. RNPs have been hypothesized to contribute to the regulation of coordinated gene expression, and defects in RNP biogenesis contribute to genome instability and disease. Despite the large number of RNPs and the importance of the molecular processes they mediate, the requirements for individual RNP complexes in mammalian development and tissue homeostasis are not well characterized. THO is an evolutionarily conserved, nuclear RNP complex that physically links nascent transcripts with the nuclear export apparatus. THO is essential for early mouse embryonic development, limiting characterization of the requirements for THO in adult tissues. To address this shortcoming, a mouse strain has been generated allowing inducible deletion of the Thoc1 gene which encodes an essential protein subunit of THO. Bone marrow reconstitution was used to generate mice in which Thoc1 deletion could be induced specifically in the hematopoietic system. We find that granulocyte macrophage progenitors have a cell autonomous requirement for Thoc1 to maintain cell growth and viability. Lymphoid lineages are not detectably affected by Thoc1 loss under the homeostatic conditions tested. Myeloid lineages may be more sensitive to Thoc1 loss due to their relatively high rate of proliferation and turnover.

  5. The Thoc1 encoded ribonucleoprotein is required for myeloid progenitor cell homeostasis in the adult mouse.

    Directory of Open Access Journals (Sweden)

    Laura Pitzonka

    Full Text Available Co-transcriptionally assembled ribonucleoprotein (RNP complexes are critical for RNA processing and nuclear export. RNPs have been hypothesized to contribute to the regulation of coordinated gene expression, and defects in RNP biogenesis contribute to genome instability and disease. Despite the large number of RNPs and the importance of the molecular processes they mediate, the requirements for individual RNP complexes in mammalian development and tissue homeostasis are not well characterized. THO is an evolutionarily conserved, nuclear RNP complex that physically links nascent transcripts with the nuclear export apparatus. THO is essential for early mouse embryonic development, limiting characterization of the requirements for THO in adult tissues. To address this shortcoming, a mouse strain has been generated allowing inducible deletion of the Thoc1 gene which encodes an essential protein subunit of THO. Bone marrow reconstitution was used to generate mice in which Thoc1 deletion could be induced specifically in the hematopoietic system. We find that granulocyte macrophage progenitors have a cell autonomous requirement for Thoc1 to maintain cell growth and viability. Lymphoid lineages are not detectably affected by Thoc1 loss under the homeostatic conditions tested. Myeloid lineages may be more sensitive to Thoc1 loss due to their relatively high rate of proliferation and turnover.

  6. (+-Rutamarin as a dual inducer of both GLUT4 translocation and expression efficiently ameliorates glucose homeostasis in insulin-resistant mice.

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    Yu Zhang

    Full Text Available Glucose transporter 4 (GLUT4 is a principal glucose transporter in response to insulin, and impaired translocation or decreased expression of GLUT4 is believed to be one of the major pathological features of type 2 diabetes mellitus (T2DM. Therefore, induction of GLUT4 translocation or/and expression is a promising strategy for anti-T2DM drug discovery. Here we report that the natural product (+-Rutamarin (Rut functions as an efficient dual inducer on both insulin-induced GLUT4 translocation and expression. Rut-treated 3T3-L1 adipocytes exhibit efficiently enhanced insulin-induced glucose uptake, while diet-induced obese (DIO mice based assays further confirm the Rut-induced improvement of glucose homeostasis and insulin sensitivity in vivo. Subsequent investigation of Rut acting targets indicates that as a specific protein tyrosine phosphatase 1B (PTP1B inhibitor Rut induces basal GLUT4 translocation to some extent and largely enhances insulin-induced GLUT4 translocation through PI3 kinase-AKT/PKB pathway, while as an agonist of retinoid X receptor α (RXRα, Rut potently increases GLUT4 expression. Furthermore, by using molecular modeling and crystallographic approaches, the possible binding modes of Rut to these two targets have been also determined at atomic levels. All our results have thus highlighted the potential of Rut as both a valuable lead compound for anti-T2DM drug discovery and a promising chemical probe for GLUT4 associated pathways exploration.

  7. Changes in Plasma Levels of N-Arachidonoyl Ethanolamine and N-Palmitoylethanolamine following Bariatric Surgery in Morbidly Obese Females with Impaired Glucose Homeostasis

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    Akhila Mallipedhi

    2015-01-01

    Full Text Available Aim. We examined endocannabinoids (ECs in relation to bariatric surgery and the association between plasma ECs and markers of insulin resistance. Methods. A study of 20 participants undergoing bariatric surgery. Fasting and 2-hour plasma glucose, lipids, insulin, and C-peptide were recorded preoperatively and 6 months postoperatively with plasma ECs (AEA, 2-AG and endocannabinoid-related lipids (PEA, OEA. Results. Gender-specific analysis showed differences in AEA, OEA, and PEA preoperatively with reductions in AEA and PEA in females postoperatively. Preoperatively, AEA was correlated with 2-hour glucose (r=0.55, P=0.01, HOMA-IR (r=0.61, P=0.009, and HOMA %S (r=-0.71, P=0.002. OEA was correlated with weight (r=0.49, P=0.03, waist circumference (r=0.52, P=0.02, fasting insulin (r=0.49, P=0.04, and HOMA-IR (r=0.48, P=0.05. PEA was correlated with fasting insulin (r=0.49, P=0.04. 2-AG had a negative correlation with fasting glucose (r=-0.59, P=0.04. Conclusion. Gender differences exist in circulating ECs in obese subjects. Females show changes in AEA and PEA after bariatric surgery. Specific correlations exist between different ECs and markers of obesity and insulin and glucose homeostasis.

  8. Gliadin affects glucose homeostasis and intestinal metagenome in C57BL/6 mice fed and high-fat diet

    DEFF Research Database (Denmark)

    Zhang, Li; Hansen, Axel Kornerup; Bahl, Martin Iain

    time, with a borderline significance of higher HOMA-IR (homeostasis model assessment of insulin resistance) after 22 weeks. Sequencing of the V3 region of the bacterial 16S rRNA genes showed that gliadin changed the abundance of 81 bacterial taxa, separating the intestinal microbial profile...

  9. Growth Hormone Receptor Antagonist Transgenic Mice Have Increased Subcutaneous Adipose Tissue Mass, Altered Glucose Homeostasis and No Change in White Adipose Tissue Cellular Senescence.

    Science.gov (United States)

    Comisford, Ross; Lubbers, Ellen R; Householder, Lara A; Suer, Ozan; Tchkonia, Tamara; Kirkland, James L; List, Edward O; Kopchick, John J; Berryman, Darlene E

    2016-01-01

    Growth hormone (GH)-resistant/deficient mice experience improved glucose homeostasis and substantially increased lifespan. Recent evidence suggests that long-lived GH-resistant/deficient mice are protected from white adipose tissue (WAT) dysfunction, including WAT cellular senescence, impaired adipogenesis and loss of subcutaneous WAT in old age. This preservation of WAT function has been suggested to be a potential mechanism for the extended lifespan of these mice. The objective of this study was to examine WAT senescence, WAT distribution and glucose homeostasis in dwarf GH receptor antagonist (GHA) transgenic mice, a unique mouse strain having decreased GH action but normal longevity. 18-month-old female GHA mice and wild-type (WT) littermate controls were used. Prior to dissection, body composition, fasting blood glucose as well as glucose and insulin tolerance tests were performed. WAT distribution was determined by weighing four distinct WAT depots at the time of dissection. Cellular senescence in four WAT depots was assessed using senescence-associated β-galactosidase staining to quantify the senescent cell burden, and real-time qPCR to quantify gene expression of senescence markers p16 and IL-6. GHA mice had a 22% reduction in total body weight, a 33% reduction in lean mass and a 10% increase in body fat percentage compared to WT controls. GHA mice had normal fasting blood glucose and improved insulin sensitivity; however, they exhibited impaired glucose tolerance. Moreover, GHA mice displayed enhanced lipid storage in the inguinal subcutaneous WAT depot (p < 0.05) and a 1.7-fold increase in extra-/intraperitoneal WAT ratio compared to controls (p < 0.05). Measurements of WAT cellular senescence showed no difference between GHA mice and WT controls. Similar to other mice with decreased GH action, female GHA mice display reduced age-related lipid redistribution and improved insulin sensitivity, but no change in cellular senescence. The similar abundance of

  10. Growth hormone receptor antagonist (GHA) transgenic mice have increased subcutaneous adipose tissue mass, altered glucose homeostasis, and no change in white adipose tissue cellular senescence

    Science.gov (United States)

    Comisford, Ross; Lubbers, Ellen R.; Householder, Lara; Suer, Ozan; Tchkonia, Tamara; Kirkland, James L.; List, Edward O.; Kopchick, John J.; Berryman, Darlene E.

    2015-01-01

    Background Growth hormone (GH) resistant/deficient mice experience improved glucose homeostasis and substantially increased lifespan. Recent evidence suggests long-lived GH resistant/deficient mice are protected from white adipose tissue (WAT) dysfunction, including WAT cellular senescence, impaired adipogenesis and loss of subcutaneous WAT in old age. This preservation of WAT function has been suggested to be a potential mechanism for the extended lifespan of these mice. OBJECTIVE The objective of this study was to examine white adipose tissue (WAT) senescence, WAT distribution, and glucose homeostasis in dwarf growth hormone receptor antagonist (GHA) transgenic mice, a unique mouse strain having decreased GH action but normal longevity. METHODS 18mo old female GHA mice and wild type (WT) littermate controls were used. Prior to dissection, body composition, fasting blood glucose, and glucose and insulin tolerance tests were performed. WAT distribution was determined by weighing four distinct WAT depots at the time of dissection. Cellular senescence in four WAT depots was assessed using senescence-associated β-galactosidase (SA-β-gal) staining to quantify the senescent cell burden and real time qPCR to quantify gene expression of senescence markers p16 and IL-6. RESULTS GHA mice had a 22% reduction in total body weight, 33% reduction in lean mass, and a 10% increase in body fat percentage compared to WT controls. GHA mice had normal fasting blood glucose and improved insulin sensitivity; however, they exhibited impaired glucose tolerance. Moreover, GHA mice displayed enhanced lipid storage in the inguinal subcutaneous WAT depot (p<.05) and a 1.7 fold increase in extra-/intraperitoneal WAT ratio compared to controls (p<.05). Measurements of WAT cellular senescence showed no difference between GHA mice and WT controls. CONCLUSIONS Similar to other mice with decreased GH action, female GHA mice display reduced age-related lipid redistribution and improved insulin

  11. Glucose homeostasis and metabolic adaptation in the pregnant and lactating sheep are affected by the level of nutrition previously provided during her late fetal life

    DEFF Research Database (Denmark)

    Husted, Sanne Munch; Nielsen, Mette Benedicte Olaf; Blache, D.

    2008-01-01

    during lactation. There was no effect of prenatal UN on glucose tolerance during G-IGTT, however, during RG-IGTT LOW was more glucose intolerant and apparently more insulin resistant compared to NORM. In conclusion, UN during late fetal life in sheep impairs subsequent pancreatic insulin secretory...... of a feed restriction period (RG-IGTT)), and a third around peak lactation (L-IGTT). LOW had lower basal insulin concentrations during lactation, and significantly decreased absolute insulin secretion during the L-IGTT in spite of similar glucose tolerance, indicating increased insulin sensitivity in LOW...... capacity during adult life, and reduces plasticity of down-regulation of insulin secretion in response to a metabolic challenge. Furthermore, prenatal UN appears to programme mechanisms, which in young adult females can shift the insulin hypersensitivity observed during early lactation into an insulin...

  12. Eating carbohydrate mostly at lunch and protein mostly at dinner within a covert hypocaloric diet influences morning glucose homeostasis in overweight/obese men.

    Science.gov (United States)

    Alves, Raquel Duarte Moreira; de Oliveira, Fernanda Cristina Esteves; Hermsdorff, Helen Hermana Miranda; Abete, Itziar; Zulet, María Angeles; Martínez, José Alfredo; Bressan, Josefina

    2014-02-01

    To evaluate the effects of two dietary patterns in which carbohydrates and proteins were eaten mostly at lunch or dinner on body weight and composition, energy metabolism, and biochemical markers in overweight/obese men. Fifty-eight men (30.0 ± 7.4 years; 30.8 ± 2.4 kg/m(2)) followed a covert hypocaloric balanced diet (-10 % of daily energy requirements) during 8 weeks. Subjects were randomly assigned to three groups: control diet (CT); diurnal carbohydrate/nocturnal protein (DCNP); and nocturnal carbohydrate/diurnal protein (NCDP). Main analyzed outcomes were weight loss, body composition, diet-induced thermogenesis (DIT), and glucose/lipid profile. In all groups, a significant decrease in body weight, BMI, and fat mass (kg and %) was verified, without differences between groups. Interestingly, within group analyses showed that the fat-free mass (kg) significantly decreased in NCDP and in CT after 8-week intervention, but not in DCNP. A detrimental increase in fasting glucose, insulin, and homeostasis model assessment of insulin resistance (HOMAIR) was verified only in DCNP, while NCDP and CT groups presented a non-significant reduction. Moreover, significant differences between DCNP and the other groups were detected for fasting insulin and HOMAIR. After the adjustments, NCDP presented a significantly higher DIT and energy expenditure after lunch, compared with DCNP, but after dinner, there were no differences among groups. Eating carbohydrates mostly at dinner and protein mostly at lunch within a hypocaloric balanced diet had similar effect on body composition and biochemical markers, but higher effect on DIT compared with control diet. Moreover, eating carbohydrates mostly at lunch and protein mostly at dinner had a deleterious impact on glucose homeostasis.

  13. Fibroblast growth factor 10-fibroblast growth factor receptor 2b mediated signaling is not required for adult glandular stomach homeostasis.

    Directory of Open Access Journals (Sweden)

    Allison L Speer

    Full Text Available The signaling pathways that are essential for gastric organogenesis have been studied in some detail; however, those that regulate the maintenance of the gastric epithelium during adult homeostasis remain unclear. In this study, we investigated the role of Fibroblast growth factor 10 (FGF10 and its main receptor, Fibroblast growth factor receptor 2b (FGFR2b, in adult glandular stomach homeostasis. We first showed that mouse adult glandular stomach expressed Fgf10, its receptors, Fgfr1b and Fgfr2b, and most of the other FGFR2b ligands (Fgf1, Fgf7, Fgf22 except for Fgf3 and Fgf20. Fgf10 expression was mesenchymal whereas FGFR1 and FGFR2 expression were mostly epithelial. Studying double transgenic mice that allow inducible overexpression of Fgf10 in adult mice, we showed that Fgf10 overexpression in normal adult glandular stomach increased epithelial proliferation, drove mucous neck cell differentiation, and reduced parietal and chief cell differentiation. Although a similar phenotype can be associated with the development of metaplasia, we found that Fgf10 overexpression for a short duration does not cause metaplasia. Finally, investigating double transgenic mice that allow the expression of a soluble form of Fgfr2b, FGF10's main receptor, which acts as a dominant negative, we found no significant changes in gastric epithelial proliferation or differentiation in the mutants. Our work provides evidence, for the first time, that the FGF10-FGFR2b signaling pathway is not required for epithelial proliferation and differentiation during adult glandular stomach homeostasis.

  14. Chickens from lines artificially selected for juvenile low and high body weight differ in glucose homeostasis and pancreas physiology.

    Science.gov (United States)

    Sumners, L H; Zhang, W; Zhao, X; Honaker, C F; Zhang, S; Cline, M A; Siegel, P B; Gilbert, E R

    2014-06-01

    Artificial selection of White Plymouth Rock chickens for juvenile (day 56) body weight resulted in two divergent genetic lines: hypophagic low weight (LWS) chickens and hyperphagic obese high weight (HWS) chickens, with the latter more than 10-fold heavier than the former at selection age. A study was designed to investigate glucose regulation and pancreas physiology at selection age in LWS chickens and HWS chickens. Oral glucose tolerance and insulin sensitivity tests revealed differences in threshold sensitivity to insulin and glucose clearance rate between the lines. Results from real-time PCR showed greater pancreatic mRNA expression of four glucose regulatory genes (preproinsulin, PPI; preproglucagon, PPG; glucose transporter 2, GLUT2; and pancreatic duodenal homeobox 1, Pdx1) in LWS chickens, than HWS chickens. Histological analysis of the pancreas revealed that HWS chickens have larger pancreatic islets, less pancreatic islet mass, and more pancreatic inflammation than LWS chickens, all of which presumably contribute to impaired glucose metabolism. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Expression of Peroxisome Proliferator-Activated Receptor-γ in Key Neuronal Subsets Regulating Glucose Metabolism and Energy Homeostasis

    OpenAIRE

    Sarruf, David A.; Yu, Fang; Nguyen, Hong T.; Williams, Diana L.; Printz, Richard L.; Niswender, Kevin D.; Schwartz, Michael W.

    2008-01-01

    In addition to increasing insulin sensitivity and adipogenesis, peroxisome proliferator-activated receptor (PPAR)-γ agonists cause weight gain and hyperphagia. Given the central role of the brain in the control of energy homeostasis, we sought to determine whether PPARγ is expressed in key brain areas involved in metabolic regulation. Using immunohistochemistry, PPARγ distribution and its colocalization with neuron-specific protein markers were investigated in rat and mouse brain sections spa...

  16. Maternal and post-weaning high-fat, high-sucrose diet modulates glucose homeostasis and hypothalamic POMC promoter methylation in mouse offspring.

    Science.gov (United States)

    Zheng, Jia; Xiao, Xinhua; Zhang, Qian; Yu, Miao; Xu, Jianping; Wang, Zhixin; Qi, Cuijuan; Wang, Tong

    2015-10-01

    Substantial evidence demonstrated that maternal dietary nutrients can significantly determine the susceptibility to developing metabolic disorders in the offspring. Therefore, we aimed to investigate the later-life effects of maternal and postweaning diets interaction on epigenetic modification of the central nervous system in the offspring. We examined the effects of dams fed a high-fat, high-sucrose (FS) diet during pregnancy and lactation and weaned to FS diet continuously until 32 weeks of age. Then, DNA methylation and gene expressions of hypothalamic proopiomelanocortin (POMC) and melanocortin receptor 4 (MC4R) were determined in the offspring. Offspring of FS diet had heavier body weight, impaired glucose tolerance, decreased insulin sensitivity and higher serum leptin level at 32-week age (p diet during gestation, lactation and into 32-week age (p diet offspring (p fat diet predisposes the offspring for obesity, glucose intolerance and insulin resistance in later life. Our findings can advance our thinking around the DNA methylation status of the promoter of the POMC and MC4R genes between long-term high-fat, high-sucrose diet and glucose homeostasis in mouse.

  17. Alpha2delta-1 in SF1+ Neurons of the Ventromedial Hypothalamus Is an Essential Regulator of Glucose and Lipid Homeostasis.

    Science.gov (United States)

    Felsted, Jennifer A; Chien, Cheng-Hao; Wang, Dongqing; Panessiti, Micaella; Ameroso, Dominique; Greenberg, Andrew; Feng, Guoping; Kong, Dong; Rios, Maribel

    2017-12-05

    The central mechanisms controlling glucose and lipid homeostasis are inadequately understood. We show that α2δ-1 is an essential regulator of glucose and lipid balance, acting in steroidogenic factor-1 (SF1) neurons of the ventromedial hypothalamus (VMH). These effects are body weight independent and involve regulation of SF1 + neuronal activity and sympathetic output to metabolic tissues. Accordingly, mice with α2δ-1 deletion in SF1 neurons exhibit glucose intolerance, altered lipolysis, and decreased cholesterol content in adipose tissue despite normal energy balance regulation. Profound reductions in the firing rate of SF1 neurons, decreased sympathetic output, and elevated circulating levels of serotonin are associated with these alterations. Normal calcium currents but reduced excitatory postsynaptic currents in mutant SF1 neurons implicate α2δ-1 in the promotion of excitatory synaptogenesis separate from its canonical role as a calcium channel subunit. Collectively, these findings identify an essential mechanism that regulates VMH neuronal activity and glycemic and lipid control and may be a target for tackling metabolic disease. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  18. Deletion of glutamate dehydrogenase in beta-cells abolishes part of the insulin secretory response not required for glucose homeostasis

    DEFF Research Database (Denmark)

    Carobbio, Stefania; Frigerio, Francesca; Rubi, Blanca

    2009-01-01

    Insulin exocytosis is regulated in pancreatic ss-cells by a cascade of intracellular signals translating glucose levels into corresponding secretory responses. The mitochondrial enzyme glutamate dehydrogenase (GDH) is regarded as a major player in this process, although its abrogation has not been...... tested yet in animal models. Here, we generated transgenic mice, named betaGlud1(-/-), with ss-cell-specific GDH deletion. Our results show that GDH plays an essential role in the full development of the insulin secretory response. In situ pancreatic perfusion revealed that glucose-stimulated insulin...... secretion was reduced by 37% in betaGlud1(-/-). Furthermore, isolated islets with either constitutive or acute adenovirus-mediated knock-out of GDH showed a 49 and 38% reduction in glucose-induced insulin release, respectively. Adenovirus-mediated re-expression of GDH in betaGlud1(-/-) islets fully restored...

  19. Meta-analysis investigating associations between healthy diet and fasting glucose and insulin levels and modification by loci associated with glucose homeostasis in data from 15 cohorts

    Science.gov (United States)

    Whether loci that influence fasting glucose (FG) and fasting insulin (FI) levels, as identified by genome-wide association studies, modify associations of diet with FG or FI is unknown. We utilized data from 15 US and European cohort studies comprising 51,289 persons without diabetes to test whether...

  20. Central serotonergic neurons activate and recruit thermogenic brown and beige fat and regulate glucose and lipid homeostasis

    DEFF Research Database (Denmark)

    McGlashon, Jacob M; Gorecki, Michelle C; Kozlowski, Amanda E

    2015-01-01

    Thermogenic brown and beige adipocytes convert chemical energy to heat by metabolizing glucose and lipids. Serotonin (5-HT) neurons in the CNS are essential for thermoregulation and accordingly may control metabolic activity of thermogenic fat. To test this, we generated mice in which the human...... adipose tissue (WAT). In parallel, blood glucose increased 3.5-fold, free fatty acids 13.4-fold, and triglycerides 6.5-fold. Similar BAT and beige fat defects occurred in Lmx1b(f/f)ePet1(Cre) mice in which 5-HT neurons fail to develop in utero. We conclude 5-HT neurons play a major role in regulating...

  1. Age-dependent alterations of glucose clearance and homeostasis are temporally separated and modulated by dietary fat

    DEFF Research Database (Denmark)

    Damgaard, Mads Thue Fejerskov; Pærregaard, Simone I.; Søgaard, Ida

    2018-01-01

    Diet- and age-dependent changes in glucose regulation in mice occur, but the temporal development, mechanisms and influence of dietary fat source remain to be defined. We followed metabolic changes in three groups of mice including a low-fat diet (LFD) reference group and two high-fat, high-sucro...

  2. Effects of transplantation and resection of a radiation-induced rat insulinoma on glucose homeostasis and the endocrine pancreas

    International Nuclear Information System (INIS)

    Flatt, P.R.; Tan, K.S.; Powell, C.J.; Swanston-Flatt, S.K.; Marks, V.; Bailey, C.J.

    1986-01-01

    Twenty-one days after s.c. subscapular transplantation of a radiation-induced insulinoma, male NEDH rats exhibited hyperinsulinaemia and hypoglycaemia. These features were associated with islet atrophy, degenerative changes in pancreatic A and B cells, and decreases in the pancreatic contents of insulin, glucagon and somatostatin. The immunoreactive glucagon and somatostatin contents of extrapancreatic tissues of insulinoma-bearing rats were unchanged. Surgical resection of the tumour resulted in an immediate fall of plasma insulin, attaining concentrations similar to those of anaesthetised control rats by 10 min. The estimated half-life of insulin was 3.5 min. Hypoglycaemia persisted until 60 min after resection, followed by hyperglycaemia of 1-2 days duration. Glucose tolerance was impaired 1 day after tumour resection despite the coexistence of raised insulin concentrations. Evidence for abnormal pancreatic B cell function was gained by injection of arginine which failed to evoke a plasma insulin response in the resected rats. Two days after resection, plasma glucose and insulin concentrations were similar to those of control rats. Plasma glucose and insulin responses to glucose and arginine were suggestive of tumour recurrence by 12 days. A single large encapsulated tumour was eventually observed in each rat, with resection giving a 17-56 day prolongation of life. (author)

  3. Differential incretin effects of GIP and GLP-1 on gastric emptying, appetite, and insulin-glucose homeostasis

    DEFF Research Database (Denmark)

    Edholm, T; Degerblad, M; Grybäck, P

    2010-01-01

    Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are major incretins with important effects on glucoregulatory functions. The aim of this study was to investigate effects of GIP and GLP-1 on gastric emptying and appetite after a mixed meal, and effects...

  4. Endothelial β-Catenin Signaling Is Required for Maintaining Adult Blood-Brain Barrier Integrity and Central Nervous System Homeostasis.

    Science.gov (United States)

    Tran, Khiem A; Zhang, Xianming; Predescu, Dan; Huang, Xiaojia; Machado, Roberto F; Göthert, Joachim R; Malik, Asrar B; Valyi-Nagy, Tibor; Zhao, You-Yang

    2016-01-12

    The blood-brain barrier (BBB) formed by brain endothelial cells interconnected by tight junctions is essential for the homeostasis of the central nervous system. Although studies have shown the importance of various signaling molecules in BBB formation during development, little is known about the molecular basis regulating the integrity of the adult BBB. Using a mouse model with tamoxifen-inducible endothelial cell-restricted disruption of ctnnb1 (iCKO), we show here that endothelial β-catenin signaling is essential for maintaining BBB integrity and central nervous system homeostasis in adult mice. The iCKO mice developed severe seizures accompanied by neuronal injury, multiple brain petechial hemorrhages, and central nervous system inflammation, and all had postictal death. Disruption of endothelial β-catenin induced BBB breakdown and downregulation of the specific tight junction proteins claudin-1 and -3 in adult brain endothelial cells. The clinical relevance of the data is indicated by the observation of decreased expression of claudin-1 and nuclear β-catenin in brain endothelial cells of hemorrhagic lesions of hemorrhagic stroke patients. These results demonstrate the prerequisite role of endothelial β-catenin in maintaining the integrity of adult BBB. The results suggest that BBB dysfunction secondary to defective β-catenin transcription activity is a key pathogenic factor in hemorrhagic stroke, seizure activity, and central nervous system inflammation. © 2015 American Heart Association, Inc.

  5. The yeast protein kinase Sch9 adjusts V-ATPase assembly/disassembly to control pH homeostasis and longevity in response to glucose availability.

    Directory of Open Access Journals (Sweden)

    Tobias Wilms

    2017-06-01

    Full Text Available The conserved protein kinase Sch9 is a central player in the nutrient-induced signaling network in yeast, although only few of its direct substrates are known. We now provide evidence that Sch9 controls the vacuolar proton pump (V-ATPase to maintain cellular pH homeostasis and ageing. A synthetic sick phenotype arises when deletion of SCH9 is combined with a dysfunctional V-ATPase, and the lack of Sch9 has a significant impact on cytosolic pH (pHc homeostasis. Sch9 physically interacts with, and influences glucose-dependent assembly/disassembly of the V-ATPase, thereby integrating input from TORC1. Moreover, we show that the role of Sch9 in regulating ageing is tightly connected with V-ATPase activity and vacuolar acidity. As both Sch9 and the V-ATPase are highly conserved in higher eukaryotes, it will be interesting to further clarify their cooperative action on the cellular processes that influence growth and ageing.

  6. Glucose production and gluconeogenesis in adults with cerebral malaria

    NARCIS (Netherlands)

    van Thien, H.; Ackermans, M. T.; Dekker, E.; Thanh Chien, V. O.; Le, T.; Endert, E.; Kager, P. A.; Romijn, J. A.; Sauerwein, H. P.

    2001-01-01

    Hypoglycaemia is an important complication in severe malaria, ascribed to an inhibition of gluconeogenesis. However, the only data available suggested that in severe malaria, total glucose production is increased. We measured glucose production and gluconeogenesis after an overnight fast in all

  7. Brain glucose and acetoacetate metabolism: a comparison of young and older adults.

    Science.gov (United States)

    Nugent, Scott; Tremblay, Sebastien; Chen, Kewei W; Ayutyanont, Napatkamon; Roontiva, Auttawut; Castellano, Christian-Alexandre; Fortier, Melanie; Roy, Maggie; Courchesne-Loyer, Alexandre; Bocti, Christian; Lepage, Martin; Turcotte, Eric; Fulop, Tamas; Reiman, Eric M; Cunnane, Stephen C

    2014-06-01

    The extent to which the age-related decline in regional brain glucose uptake also applies to other important brain fuels is presently unknown. Ketones are the brain's major alternative fuel to glucose, so we developed a dual tracer positron emission tomography protocol to quantify and compare regional cerebral metabolic rates for glucose and the ketone, acetoacetate. Twenty healthy young adults (mean age, 26 years) and 24 healthy older adults (mean age, 74 years) were studied. In comparison with younger adults, older adults had 8 ± 6% (mean ± SD) lower cerebral metabolic rates for glucose in gray matter as a whole (p = 0.035), specifically in several frontal, temporal, and subcortical regions, as well as in the cingulate and insula (p ≤ 0.01, false discovery rate correction). The effect of age on cerebral metabolic rates for acetoacetate in gray matter did not reach significance (p = 0.11). Rate constants (min(-1)) of glucose (Kg) and acetoacetate (Ka) were significantly lower (-11 ± 6%; [p = 0.005], and -19 ± 5%; [p = 0.006], respectively) in older adults compared with younger adults. There were differential effects of age on Kg and Ka as seen by significant interaction effects in the caudate (p = 0.030) and post-central gyrus (p = 0.023). The acetoacetate index, which expresses the scaled residuals of the voxel-wise linear regression of glucose on ketone uptake, identifies regions taking up higher or lower amounts of acetoacetate relative to glucose. The acetoacetate index was higher in the caudate of young adults when compared with older adults (p ≤ 0.05 false discovery rate correction). This study provides new information about glucose and ketone metabolism in the human brain and a comparison of the extent to which their regional use changes during normal aging. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Chickens from lines artificially selected for juvenile low and high body weight differ in glucose homeostasis and pancreas physiology

    OpenAIRE

    Sumners, Lindsay Hart

    2015-01-01

    Early pancreatectomy experiments performed in ducks and pigeons at the end of the 19th century revealed that avians, unlike mammals, do not display signs of diabetes. Relative to mammals, birds are considered hyperglycemic, displaying fasting blood glucose concentrations twice that of a normal human. While circulating levels of insulin are similar in avians and mammals, and structure and function of the insulin receptor are also conserved among vertebrate species, birds do not experience de...

  9. The role of GluN2A and GluN2B NMDA receptor subunits in AgRP and POMC neurons on body weight and glucose homeostasis

    Directory of Open Access Journals (Sweden)

    Aykut Üner

    2015-10-01

    Conclusions: GluN2B-containing NMDA receptors in AgRP neurons play a critical role in central control of body weight homeostasis and blood glucose balance via mechanisms that likely involve regulation of AgRP neuronal survival and structure, and modulation of hypothalamic leptin action.

  10. Long-term treatment with the sodium glucose cotransporter 2 inhibitor, dapagliflozin, ameliorates glucose homeostasis and diabetic nephropathy in db/db mice.

    Directory of Open Access Journals (Sweden)

    Naoto Terami

    Full Text Available Inhibition of sodium glucose cotransporter 2 (SGLT2 has been reported as a new therapeutic strategy for treating diabetes. However, the effect of SGLT2 inhibitors on the kidney is unknown. In addition, whether SGLT2 inhibitors have an anti-inflammatory or antioxidative stress effect is still unclear. In this study, to resolve these issues, we evaluated the effects of the SGLT2 inhibitor, dapagliflozin, using a mouse model of type 2 diabetes and cultured proximal tubular epithelial (mProx24 cells. Male db/db mice were administered 0.1 or 1.0 mg/kg of dapagliflozin for 12 weeks. Body weight, blood pressure, blood glucose, hemoglobin A1c, albuminuria and creatinine clearance were measured. Mesangial matrix accumulation and interstitial fibrosis in the kidney and pancreatic β-cell mass were evaluated by histological analysis. Furthermore, gene expression of inflammatory mediators, such as osteopontin, monocyte chemoattractant protein-1 and transforming growth factor-β, was evaluated by quantitative reverse transcriptase-PCR. In addition, oxidative stress was evaluated by dihydroethidium and NADPH oxidase 4 staining. Administration of 0.1 or 1.0 mg/kg of dapagliflozin ameliorated hyperglycemia, β-cell damage and albuminuria in db/db mice. Serum creatinine, creatinine clearance and blood pressure were not affected by administration of dapagliflozin, but glomerular mesangial expansion and interstitial fibrosis were suppressed in a dose-dependent manner. Dapagliflozin treatment markedly decreased macrophage infiltration and the gene expression of inflammation and oxidative stress in the kidney of db/db mice. Moreover, dapagliflozin suppressed the high-glucose-induced gene expression of inflammatory cytokines and oxidative stress in cultured mProx24 cells. These data suggest that dapagliflozin ameliorates diabetic nephropathy by improving hyperglycemia along with inhibiting inflammation and oxidative stress.

  11. Deletion of the Androgen Receptor in Adipose Tissue in Male Mice Elevates Retinol Binding Protein 4 and Reveals Independent Effects on Visceral Fat Mass and on Glucose Homeostasis

    Science.gov (United States)

    McInnes, Kerry J.; Smith, Lee B.; Hunger, Nicole I.; Saunders, Philippa T.K.; Andrew, Ruth; Walker, Brian R.

    2012-01-01

    Testosterone deficiency is epidemic in obese ageing males with type 2 diabetes, but the direction of causality remains unclear. Testosterone-deficient males and global androgen receptor (AR) knockout mice are insulin resistant with increased fat, but it is unclear whether AR signaling in adipose tissue mediates body fat redistribution and alters glucose homoeostasis. To investigate this, mice with selective knockdown of AR in adipocytes (fARKO) were generated. Male fARKO mice on normal diet had reduced perigonadal fat but were hyperinsulinemic and by age 12 months, were insulin deficient in the absence of obesity. On high-fat diet, fARKO mice had impaired compensatory insulin secretion and hyperglycemia, with increased susceptibility to visceral obesity. Adipokine screening in fARKO mice revealed a selective increase in plasma and intra-adipose retinol binding protein 4 (RBP4) that preceded obesity. AR activation in murine 3T3 adipocytes downregulated RBP4 mRNA. We conclude that AR signaling in adipocytes not only protects against high-fat diet–induced visceral obesity but also regulates insulin action and glucose homeostasis, independently of adiposity. Androgen deficiency in adipocytes in mice resembles human type 2 diabetes, with early insulin resistance and evolving insulin deficiency. PMID:22415878

  12. Apolipoprotein E Genotype and Sex Influence Glucose Tolerance in Older Adults: A Cross-Sectional Study

    Directory of Open Access Journals (Sweden)

    Angela J. Hanson

    2016-03-01

    Full Text Available Background: Glucose intolerance and apolipoprotein ε4 allele (E4+ are risk factors for Alzheimer's disease (AD. Insulin sensitizers show promise for treating AD, but are less effective in E4+ individuals. Little is known about how the APOE genotype influences glucose metabolism. Methods: Cross-sectional analysis of 319 older adults who underwent oral glucose tolerance tests; a subset had insulin, amyloid beta (Aβ42, and Mini Mental Status Examination. Glucose and insulin patterns with respect to cognitive diagnosis, E4 status, and sex were examined with analysis of covariance and Pearson correlation. Results: People with cognitive impairment had higher fasting insulin levels. E4 status did not affect fasting glucose values, whereas men had higher fasting glucose levels than women. E4+ men had the lowest and E4+ women had the highest glucose levels, compared to E4- groups; insulin did not differ by sex or E4 group. E4 status and sex moderated correlations between metabolic measures and AD risk factors including age and Aβ. Conclusions: Insulin resistance was associated with cognitive impairment, and sex, E4 status, and glucose values are interrelated in older adults at risk of AD. Understanding glucose metabolism for different APOE and sex groups may help elucidate differences in therapeutic responses.

  13. Influence of High Aspect Ratio Vessel Cell Culture on TNF-Alpha, Insulin Secretion and Glucose Homeostasis in Pancreatic Islets of Langerhans from Wistar Furth Rats

    Science.gov (United States)

    Tobin, Brian W.a; Leeper-Woodford, Sandra K.

    1999-01-01

    The present studies were carried out to determine the influence of a ground based microgravity paradigm, utilizing the High Aspect Ratio Vessel (HARV) cell culture upon lipopolysaccharide (LPS) stimulated tumor necrosis factor alpha (TNF-alpha) production of pancreatic islets of Langerhans. An additional aim was to elucidate alterations in insulin secretion and glucose utilization using the HARV low shear, gravity averaged vector, cell culture technique. Islets were isolated (1726 +/- 117, 150 micron islet equivalent units) from Wistar Furth rats and assigned to four treatment groups: 1) HARV, 2) HARV plus LPS, 3) static culture, 4) static culture plus LPS. Following 48 hours of culture, insulin concentration was increased in both HARV and static cultures (palpha (L929 cytotoxicity assay) and was measured at selected time points for 48 hours. TNF-alpha was significantly increased in LPS-induced HARV and static cultures, yet the increase was more pronounced in the static culture group (palpha is associated with a decreased insulin secretion is intriguing, both as it relates to in-flight investigations, and as it may provide insight into the pathophysiology of Type I and Type 11 diabetes. Glucose concentration in islet medium was lesser throughout the experiment in static cultures, suggesting a decreased reliance upon glucose as a metabolic substrate in the islets cultured in HARVS. In conclusion, the present studies demonstrate alterations in LPS induced TNF-alpha production of pancreatic islets of Langerhans, favoring a lesser TNF production in the microgravity HARV paradigm. Additionally, alterations in fuel homeostasis may be promulgated by HARV culture. The clinical and physiological significance of these observations remains to be determined.

  14. Higher fasting glucose is associated with poorer cognition among healthy young adults.

    Science.gov (United States)

    Hawkins, Misty A W; Gunstad, John; Calvo, Dayana; Spitznagel, Mary Beth

    2016-02-01

    Obesity is associated with cognitive deficits; however, the mechanisms are unclear, especially among otherwise healthy adults. Our objectives were to examine (a) whether obesity is linked to elevations in fasting glucose and (b) whether these elevations are associated with cognitive impairment among otherwise healthy young adults. Participants were 35 normal weight adults and 35 young adults with obesity who completed a task from the Automated Neuropsychological Assessment Metrics-4 (ANAM-4). Measured body mass index (BMI) and fasting blood glucose levels (mg/dL) were examined. Persons with obesity had higher fasting glucose levels than normal weight persons (p = .03). After applying Bonferroni correction for multiple tests, higher fasting glucose predicted less accurate performance on tests of inhibitory control: Go/No-Go Commission Errors (β = .33, p = .004). No effects were observed for sustained attention or working memory (ps ≥. 049). Persons with glucose levels in the prediabetes range had nearly twice as many errors as those with normal glucose, a large effect that was independent of BMI. Young adults who were obese but otherwise healthy had higher fasting glucose levels compared with normal weight peers. Higher glucose levels were associated with poorer cognitive performance on tests of inhibitory control, especially among individuals with prediabetes levels. Thus, subclinical elevations in blood glucose may contribute to cognitive impairment and, ultimately, greater impulsivity-well in advance of the development of chronic disease states (e.g., insulin resistance or Type 2 diabetes) and independently of excess adiposity--though prospective studies are needed to determine directionality of this relationship. (c) 2016 APA, all rights reserved).

  15. Repeated Plyometric Exercise Attenuates Blood Glucose in Healthy Adults.

    Science.gov (United States)

    Barillas, Saldiam R; Watkins, Casey M; Wong, Megan A; Dobbs, Ian J; Archer, David C; Munger, Cameron N; Galpin, Andrew J; Coburn, Jared W; Brown, Lee E

    2017-01-01

    Plyometric exercise is popular in commercial exercise programs aiming to maximize energy expenditure for weight loss. However, the effect of plyometric exercise on blood glucose is unknown. The purpose of this study was to investigate the effect of relatively high intensity plyometric exercise on blood glucose. Thirteen subjects (6 females age= 21.8 ± 1.0 yrs.; height= 163.7 ± 7.8 cm; mass= 60.8 ± 6.7 kg and 7 males age= 22.0 ± 2.6 yrs.; height= 182.3 ± 3.6 cm; mass= 87.4 ± 12.5 kg) volunteered to participate. Subjects completed two random conditions on two separate days, consisting of either five sets of 10 maximal effort countermovement squat jumps (SJ) with 50 seconds' rest between sets or quiet sitting (SIT) for the time equated to the SJ duration (~4min). Immediately after each condition, subjects drank 75g of anhydrous glucose (CHO) in 100ml of water. Blood glucose measurements were taken via finger prick pre and immediately post SJ or SIT, and 5, 15, 30, and 60 min post. A 2×6 (condition × time) ANOVA revealed a significant interaction where SJ blood glucose was lower at 15 (114.0 ± 14.6 mg/dl) and 30 (142.1 ± 22.5 mg/dl) min compared to SIT (15min 130.8 ± 14.0 mg/dl and 30min 159.3 ± 21.0 mg/dl). The current plyometric protocol attenuated CHO-induced blood glucose at 15 and 30 min. This may be due to increased physiological stress applied to the muscles, thus increasing muscular glucose uptake.

  16. Specific Sirt1 Activator-mediated Improvement in Glucose Homeostasis Requires Sirt1-Independent Activation of AMPK

    Directory of Open Access Journals (Sweden)

    Sung-Jun Park

    2017-04-01

    Full Text Available The specific Sirt1 activator SRT1720 increases mitochondrial function in skeletal muscle, presumably by activating Sirt1. However, Sirt1 gain of function does not increase mitochondrial function, which raises a question about the central role of Sirt1 in SRT1720 action. Moreover, it is believed that the metabolic effects of SRT1720 occur independently of AMP-activated protein kinase (AMPK, an important metabolic regulator that increases mitochondrial function. Here, we show that SRT1720 activates AMPK in a Sirt1-independent manner and SRT1720 activates AMPK by inhibiting a cAMP degrading phosphodiesterase (PDE in a competitive manner. Inhibiting the cAMP effector protein Epac prevents SRT1720 from activating AMPK or Sirt1 in myotubes. Moreover, SRT1720 does not increase mitochondrial function or improve glucose tolerance in AMPKα2 knockout mice. Interestingly, weight loss induced by SRT1720 is not sufficient to improve glucose tolerance. Therefore, contrary to current belief, the metabolic effects produced by SRT1720 require AMPK, which can be activated independently of Sirt1.

  17. Experimental study on effect of hydroalcoholic extract of Emblica officinalis fruits on glucose homeostasis and metabolic parameters

    Science.gov (United States)

    Patel, Snehal S.; Goyal, Ramesh K.; Shah, Rajendra S.; Tirgar, Pravin R.; Jadav, Pinakin D.

    2013-01-01

    Polyphenols from natural source are potential therapeutics that act alone or supplement anti-diabetic drugs in the prevention and treatment of diabetes. The present investigation was undertaken to study the effect of hydroalcoholic extract (HE) of fruits of Emblica officinalis on type 1 diabetic rats. Diabetes was induced by streptozotocin (STZ) (45 mg/kg i.v.). HE (100 mg/kg, p.o.) was administered for 4 weeks and at the end of treatment, blood samples were collected and analyzed for various biochemical parameters. STZ produced a diabetic state exhibiting all the cardinal symptoms such as loss of body weight, polydipsia, polyuria, glucosuria, polyphagia, hypoinsulinemia, and hyperglycemia associated with hypercholesterolemia and hypertriglyceridemia. Treatment with HE prevented cardinal symptoms and caused significant decrease in fasting serum glucose, AUCglucose, cholesterol, triglyceride, low-density lipoprotein (LDL) and very LDL in diabetic rats. However, insulin, AUCinsulin, and serum high-density lipoprotein level were not significantly altered by treatment. Treatment also reduced lipid peroxidation and increased anti-oxidant parameters in the liver homogenates of diabetic rats. Polyphenol enriched fraction of HE significantly improved disarranged carbohydrate and lipid metabolism of chemically induced diabetes in rats. The mechanism of its anti-diabetic activity appears to be either improvement in peripheral glucose utilization, increased insulin sensitivity, or anti-oxidant property. PMID:24696584

  18. Diabetes mellitus and impaired glucose tolerance in urban adult population

    Directory of Open Access Journals (Sweden)

    Walter Rodrigues Júnior

    2014-01-01

    Full Text Available Objective: Estimating the prevalence of diabetes mellitus (DM and impaired glucose tolerance (IGT in the urban population aged between 30 and 69 years in the municipality of Campo Grande, state of Mato Grosso do Sul, Brazil. Methods: Population-based cross-sectional study conducted between October/2009 and February/2011. The investigation included the determination of fasting glucose and participants with blood glucose ≥ 200 mg/dL were considered diabetic. Nondiabetic patients, which showed blood glucose ≥ 100 mg/dL and < 200 mg/dL, underwent an oral glucose tolerance test (OGTT to investigate whether they had DM or IGT. Results: 1.429 individuals participated in this investigation. The general prevalence, adjusted for sex and age, were: 12.3% for DM (95%CI: 10.5 to 13.9% and 7.1% for IGT (95%CI: 5.7 to 8.4%. There was a higher prevalence of DM with increasing age in people with low educational level, family history of diabetes, overweight, obesity and central obesity. Among diabetic patients (n = 195, 25% were unaware they had the disease and were diagnosed through investigation. Among patients who already knew they had DM (n = 146, 37% were unaware of the potential chronic complications. Conclusion: This study confirms the increased prevalence of DM in Brazil and emphasizes the need for early diagnosis, as well as the importance of strict adherence to medical treatment in order to prevent its much feared complications.

  19. Maintenance of the adult Drosophila intestine: all roads lead to homeostasis.

    Science.gov (United States)

    Guo, Zheng; Lucchetta, Elena; Rafel, Neus; Ohlstein, Benjamin

    2016-10-01

    Maintenance of tissue homeostasis is critical in tissues with high turnover such as the intestinal epithelium. The intestinal epithelium is under constant cellular assault due to its digestive functions and its function as a barrier to chemical and bacterial insults. The resulting high rate of cellular turnover necessitates highly controlled mechanisms of regeneration to maintain the integrity of the tissue over the lifetime of the organism. Transient increase in stem cell proliferation is a commonly used and elaborate mechanism to ensure fast and efficient repair of the gut. However, tissue repair is not limited to regulating ISC proliferation, as emerging evidence demonstrates that the Drosophila intestine uses multiple strategies to ensure proper tissue homeostasis that may also extend to other tissues. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Stomach Organ and Cell Lineage Differentiation: From?Embryogenesis to Adult Homeostasis

    OpenAIRE

    Willet, Spencer G.; Mills, Jason C.

    2016-01-01

    Gastric diseases cause considerable worldwide burden. However, the stomach is still poorly understood in terms of the molecularâcellular processes that govern its development and homeostasis. In particular, the complex relationship between the differentiated cell types located within the stomach and the stem and progenitor cells that give rise to them is significantly understudied relative to other organs. In this review, we highlight the current state of the literature relating to specificat...

  1. Sodium Orthovanadate and Trigonella Foenum Graecum Prevents Neuronal Parameters Decline and Impaired Glucose Homeostasis in Alloxan Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Pardeep Kumar

    2015-01-01

    Full Text Available Hyperglycemia is the most important contributor in the onset and progress of diabetic complications mainly by producing oxidative stress. The present study was carried out to observe, the antihyperglycemic effect of sodium orthovanadate (SOV and Trigonella foenum graecum seed powder (TSP administration on blood glucose and insulin levels, membrane linked enzymes (monoamine oxidase, acetylcholinesterase, Ca2+ATPase, intracellular calcium (Ca2+ levels, lipid peroxidation, membrane fluidity and neurolipofuscin accumulation in brain of the alloxan induced diabetic rats and to see whether the treatment with SOV and TSP was capable of reversing the diabetic effects. Diabetes was induced by administration of alloxan monohydrate (15 mg/100 g body weight and rats were treated with 2 IU insulin, 0.6 mg/ml SOV, 5% TSP in the diet and a combination of 0.2 mg/ml SOV and 5% TSP separately for three weeks. Diabetic rats showed hyperglycemia with almost four fold high blood glucose levels. Activities of acetylcholinesterase and Ca2+ATPase decreased in diabetic rat brain. Diabetic rats exhibited an increased level of intracellular Ca2+ levels, lipid peroxidation, neurolipofuscin accumulations and monoamine oxidase activity. Treatment of diabetic rats with insulin, TSP, SOV and a combined therapy of lower dose of SOV with TSP revived normoglycemia and restored the altered level of membrane bound enzymes, lipid peroxidation and neurolipofuscin accumulation. Our results showed that lower doses of SOV (0.2 mg/ml could be used in combination with TSP in normalization of altered metabolic parameters and membrane linked enzymes without any harmful side effect.

  2. TAS2R38 and its influence on smoking behavior and glucose homeostasis in the German Sorbs.

    Directory of Open Access Journals (Sweden)

    Maria Keller

    Full Text Available BACKGROUND: Genetic variants within the bitter taste receptor gene TAS2R38 are associated with sensitivity to bitter taste and are related to eating behavior in the Amish population. Sensitivity to bitter taste is further related to anthropometric traits in an genetically isolated Italian population. We tested whether the TAS2R38 variants (rs713598; rs1726866 and rs10246939 may be related to eating behavior, anthropometric parameters, metabolic traits and consumer goods intake in the German Sorbs. MATERIALS AND METHODS: The three SNPs were genotyped in a total cohort of 1007 individuals (male/female: 405/602. The German version of the three-factor eating questionnaire was completed by 548 individuals. Genetic association analyses for smoking behavior, alcohol and coffee intake, eating behavior factors (restraint, disinhibition and hunger and other metabolic traits were analyzed. Further, by combining the three SNPs we applied comparative haplotype analyses categorizing PAV (proline-alanine-valine carriers (tasters vs. homozygous AVI (alanin-valine-isoleucine carriers (non-tasters. RESULTS: Significant associations of genetic variants within TAS2R38 were identified with percentage of body fat, which were driven by associations in women. In men, we observed significant associations with 30 min plasma glucose, and area under the curve for plasma glucose (0-120 min (all adjusted P≤0.05. Further, we found that carriers of at least one PAV allele show significantly lower cigarette smoking per day (P = 0.002 as well as, albeit non-significant, lower alcohol intake. We did not confirm previously reported associations between genetic variants of TAS2R38 and eating behavior. CONCLUSION: Our data suggest that genetic variation in TAS2R38 is related to individual body composition measures and may further influence consumer goods intake in the Sorbs possibly via individual sensitivity to bitter taste.

  3. TAS2R38 and Its Influence on Smoking Behavior and Glucose Homeostasis in the German Sorbs

    Science.gov (United States)

    Keller, Maria; Liu, Xuanshi; Wohland, Tobias; Rohde, Kerstin; Gast, Marie-Therese; Stumvoll, Michael; Kovacs, Peter; Tönjes, Anke; Böttcher, Yvonne

    2013-01-01

    Background Genetic variants within the bitter taste receptor gene TAS2R38 are associated with sensitivity to bitter taste and are related to eating behavior in the Amish population. Sensitivity to bitter taste is further related to anthropometric traits in an genetically isolated Italian population. We tested whether the TAS2R38 variants (rs713598; rs1726866 and rs10246939) may be related to eating behavior, anthropometric parameters, metabolic traits and consumer goods intake in the German Sorbs. Materials and Methods The three SNPs were genotyped in a total cohort of 1007 individuals (male/female: 405/602). The German version of the three-factor eating questionnaire was completed by 548 individuals. Genetic association analyses for smoking behavior, alcohol and coffee intake, eating behavior factors (restraint, disinhibition and hunger) and other metabolic traits were analyzed. Further, by combining the three SNPs we applied comparative haplotype analyses categorizing PAV (proline-alanine-valine) carriers (tasters) vs. homozygous AVI (alanin-valine-isoleucine) carriers (non-tasters). Results Significant associations of genetic variants within TAS2R38 were identified with percentage of body fat, which were driven by associations in women. In men, we observed significant associations with 30 min plasma glucose, and area under the curve for plasma glucose (0–120 min) (all adjusted P≤0.05). Further, we found that carriers of at least one PAV allele show significantly lower cigarette smoking per day (P = 0.002) as well as, albeit non-significant, lower alcohol intake. We did not confirm previously reported associations between genetic variants of TAS2R38 and eating behavior. Conclusion Our data suggest that genetic variation in TAS2R38 is related to individual body composition measures and may further influence consumer goods intake in the Sorbs possibly via individual sensitivity to bitter taste. PMID:24312479

  4. Sodium Orthovanadate and Trigonella Foenum Graecum Prevents Neuronal Parameters Decline and Impaired Glucose Homeostasis in Alloxan Diabetic Rats.

    Science.gov (United States)

    Kumar, Pardeep; Taha, Asia; Kumar, Nitin; Kumar, Vinod; Baquer, Najma Zaheer

    2015-01-01

    Hyperglycemia is the most important contributor in the onset and progress of diabetic complications mainly by producing oxidative stress. The present study was carried out to observe, the antihyperglycemic effect of sodium orthovanadate (SOV) and Trigonella foenum graecum seed powder (TSP) administration on blood glucose and insulin levels, membrane linked enzymes (monoamine oxidase, acetylcholinesterase, Ca2+ATPase), intracellular calcium (Ca2+) levels, lipid peroxidation, membrane fluidity and neurolipofuscin accumulation in brain of the alloxan induced diabetic rats and to see whether the treatment with SOV and TSP was capable of reversing the diabetic effects. Diabetes was induced by administration of alloxan monohydrate (15 mg/100 g body weight) and rats were treated with 2 IU insulin, 0.6 mg/ml SOV, 5% TSP in the diet and a combination of 0.2 mg/ml SOV and 5% TSP separately for three weeks. Diabetic rats showed hyperglycemia with almost four fold high blood glucose levels. Activities of acetylcholinesterase and Ca2+ATPase decreased in diabetic rat brain. Diabetic rats exhibited an increased level of intracellular Ca2+ levels, lipid peroxidation, neurolipofuscin accumulations and monoamine oxidase activity. Treatment of diabetic rats with insulin, TSP, SOV and a combined therapy of lower dose of SOV with TSP revived normoglycemia and restored the altered level of membrane bound enzymes, lipid peroxidation and neurolipofuscin accumulation. Our results showed that lower doses of SOV (0.2 mg/ml) could be used in combination with TSP in normalization of altered metabolic parameters and membrane linked enzymes without any harmful side effect.

  5. Blood glucose response of normoglycemic adults fed breakfast ...

    African Journals Online (AJOL)

    Gift

    Effect of high fibre leguminous products in breakfast porridges, made from Afzelia Africana (AA), ... Fasting and postprandial blood glucose levels were taken at 30 min interval for 2 .... ml to CSS and each was cooked (stirred continuously) for 10 min to ..... prevalence of diabetes, overweight/obesity and physical inactivity in.

  6. Hepatic Mitochondrial Pyruvate Carrier 1 Is Required for Efficient Regulation of Gluconeogenesis and Whole-Body Glucose Homeostasis.

    Science.gov (United States)

    Gray, Lawrence R; Sultana, Mst Rasheda; Rauckhorst, Adam J; Oonthonpan, Lalita; Tompkins, Sean C; Sharma, Arpit; Fu, Xiaorong; Miao, Ren; Pewa, Alvin D; Brown, Kathryn S; Lane, Erin E; Dohlman, Ashley; Zepeda-Orozco, Diana; Xie, Jianxin; Rutter, Jared; Norris, Andrew W; Cox, James E; Burgess, Shawn C; Potthoff, Matthew J; Taylor, Eric B

    2015-10-06

    Gluconeogenesis is critical for maintenance of euglycemia during fasting. Elevated gluconeogenesis during type 2 diabetes (T2D) contributes to chronic hyperglycemia. Pyruvate is a major gluconeogenic substrate and requires import into the mitochondrial matrix for channeling into gluconeogenesis. Here, we demonstrate that the mitochondrial pyruvate carrier (MPC) comprising the Mpc1 and Mpc2 proteins is required for efficient regulation of hepatic gluconeogenesis. Liver-specific deletion of Mpc1 abolished hepatic MPC activity and markedly decreased pyruvate-driven gluconeogenesis and TCA cycle flux. Loss of MPC activity induced adaptive utilization of glutamine and increased urea cycle activity. Diet-induced obesity increased hepatic MPC expression and activity. Constitutive Mpc1 deletion attenuated the development of hyperglycemia induced by a high-fat diet. Acute, virally mediated Mpc1 deletion after diet-induced obesity decreased hyperglycemia and improved glucose tolerance. We conclude that the MPC is required for efficient regulation of gluconeogenesis and that the MPC contributes to the elevated gluconeogenesis and hyperglycemia in T2D. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Markers of insulin resistance and carotid atherosclerosis. A comparison of the homeostasis model assessment and triglyceride glucose index.

    Science.gov (United States)

    Irace, C; Carallo, C; Scavelli, F B; De Franceschi, M S; Esposito, T; Tripolino, C; Gnasso, A

    2013-07-01

    The present investigation was designed to test the association between carotid atherosclerosis and two simple markers of insulin resistance, i.e. HOMA-Index and TyG-Index. The study was performed in two different cohorts. In the first cohort, 330 individuals were enrolled. Blood pressure, lipids, glucose, waist and cigarette smoking were evaluated. HOMA-IR and TyG-Index were calculated as markers of prevalent hepatic and muscular insulin resistance respectively. Carotid atherosclerosis was assessed by Doppler ultrasonography. The association between cardiovascular risk factors, markers of insulin resistance and carotid atherosclerosis was assessed by multiple logistic regression analyses. In the second cohort, limited to the evaluation of TyG-Index, 1432 subjects were studied. In the first cohort, TyG-Index was significantly associated with carotid atherosclerosis in a model including age, sex, diabetes, cigarette smoking and LDL cholesterol, while HOMA-IR was not. When components of metabolic syndrome were added to the model as dichotomous variables (absent/present), TyG-Index retained its predictive power. The same result was obtained when the metabolic syndrome was added to the model (absence/presence). The association between TyG-Index and carotid atherosclerosis was confirmed in the second cohort. The present findings suggest that TyG-Index is better associated with carotid atherosclerosis than HOMA-IR. © 2013 John Wiley & Sons Ltd.

  8. IL-6 Improves Energy and Glucose Homeostasis in Obesity via Enhanced Central IL-6 trans-Signaling.

    Science.gov (United States)

    Timper, Katharina; Denson, Jesse Lee; Steculorum, Sophie Marie; Heilinger, Christian; Engström-Ruud, Linda; Wunderlich, Claudia Maria; Rose-John, Stefan; Wunderlich, F Thomas; Brüning, Jens Claus

    2017-04-11

    Interleukin (IL)-6 engages similar signaling mechanisms to leptin. Here, we find that central application of IL-6 in mice suppresses feeding and improves glucose tolerance. In contrast to leptin, whose action is attenuated in obesity, the ability of IL-6 to suppress feeding is enhanced in obese mice. IL-6 suppresses feeding in the absence of neuronal IL-6-receptor (IL-6R) expression in hypothalamic or all forebrain neurons of mice. Conversely, obese mice exhibit increased soluble IL-6R levels in the cerebrospinal fluid. Blocking IL-6 trans-signaling in the CNS abrogates the ability of IL-6 to suppress feeding. Furthermore, gp130 expression is enhanced in the paraventricular nucleus of the hypothalamus (PVH) of obese mice, and deletion of gp130 in the PVH attenuates the beneficial central IL-6 effects on metabolism. Collectively, these experiments indicate that IL-6 trans-signaling is enhanced in the CNS of obese mice, allowing IL-6 to exert its beneficial metabolic effects even under conditions of leptin resistance. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  9. IL-6 Improves Energy and Glucose Homeostasis in Obesity via Enhanced Central IL-6 trans-Signaling

    Directory of Open Access Journals (Sweden)

    Katharina Timper

    2017-04-01

    Full Text Available Interleukin (IL-6 engages similar signaling mechanisms to leptin. Here, we find that central application of IL-6 in mice suppresses feeding and improves glucose tolerance. In contrast to leptin, whose action is attenuated in obesity, the ability of IL-6 to suppress feeding is enhanced in obese mice. IL-6 suppresses feeding in the absence of neuronal IL-6-receptor (IL-6R expression in hypothalamic or all forebrain neurons of mice. Conversely, obese mice exhibit increased soluble IL-6R levels in the cerebrospinal fluid. Blocking IL-6 trans-signaling in the CNS abrogates the ability of IL-6 to suppress feeding. Furthermore, gp130 expression is enhanced in the paraventricular nucleus of the hypothalamus (PVH of obese mice, and deletion of gp130 in the PVH attenuates the beneficial central IL-6 effects on metabolism. Collectively, these experiments indicate that IL-6 trans-signaling is enhanced in the CNS of obese mice, allowing IL-6 to exert its beneficial metabolic effects even under conditions of leptin resistance.

  10. Leucine supplementation improves adiponectin and total cholesterol concentrations despite the lack of changes in adiposity or glucose homeostasis in rats previously exposed to a high-fat diet

    Directory of Open Access Journals (Sweden)

    Donato Jose

    2011-09-01

    Full Text Available Abstract Background Studies suggest that leucine supplementation (LS has a therapeutic potential to prevent obesity and to promote glucose homeostasis. Furthermore, regular physical exercise is a widely accepted strategy for body weight maintenance and also for the prevention of obesity. The aim of this study was to determine the effect of chronic LS alone or combined with endurance training (ET as potential approaches for reversing the insulin resistance and obesity induced by a high-fat diet (HFD in rats. Methods Forty-seven rats were randomly divided into two groups. Animals were fed a control diet-low fat (n = 10 or HFD (n = 37. After 15 weeks on HFD, all rats received the control diet-low fat and were randomly divided according to treatment: reference (REF, LS, ET, and LS+ET (n = 7-8 rats per group. After 6 weeks of treatment, the animals were sacrificed and body composition, fat cell volume, and serum concentrations of total cholesterol, HDL-cholesterol, triacylglycerol, glucose, adiponectin, leptin and tumor necrosis factor-alpha (TNF-α were analyzed. Results At the end of the sixth week of treatment, there was no significant difference in body weight between the REF, LS, ET and LS+ET groups. However, ET increased lean body mass in rats (P = 0.019. In addition, ET was more effective than LS in reducing adiposity (P = 0.019, serum insulin (P = 0.022 and TNF-α (P = 0.044. Conversely, LS increased serum adiponectin (P = 0.021 levels and reduced serum total cholesterol concentration (P = 0.042. Conclusions The results showed that LS had no beneficial effects on insulin sensitivity or adiposity in previously obese rats. On the other hand, LS was effective in increasing adiponectin levels and in reducing total cholesterol concentration.

  11. Effect of ground cinnamon on postprandial blood glucose concentration in normal-weight and obese adults.

    Science.gov (United States)

    Magistrelli, Ashley; Chezem, Jo Carol

    2012-11-01

    In healthy normal-weight adults, cinnamon reduces blood glucose concentration and enhances insulin sensitivity. Insulin resistance, resulting in increased fasting and postprandial blood glucose and insulin levels, is commonly observed in obese individuals. The objective of the study was to compare declines in postprandial glycemic response in normal-weight and obese subjects with ingestion of 6 g ground cinnamon. In a crossover study, subjects consumed 50 g available carbohydrate in instant farina cereal, served plain or with 6 g ground cinnamon. Blood glucose concentration, the main outcome measure, was assessed at minutes 0, 15, 30, 45, 60, 90, and 120. Repeated-measures analysis of variance evaluated the effects of body mass index (BMI) group, dietary condition, and time on blood glucose. Paired t-test assessed blood glucose at individual time points and glucose area under the curve (AUC) between dietary conditions. Thirty subjects between the ages of 18 and 30 years, 15 with BMIs between 18.5 and 24.9 and 15 with BMIs of 30.0 or more, completed the study. There was no significant difference in blood glucose between the two BMI groups at any time point. However, in a combined analysis of all subjects, the addition of cinnamon to the cereal significantly reduced 120-minute glucose AUC (P=0.008) and blood glucose at 15 (P=0.001), 30 (Pblood glucose was significantly higher with cinnamon consumption (Pglucose response in normal weight and obese adults. Copyright © 2012 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

  12. Methylphenidate increases glucose uptake in the brain of young and adult rats.

    Science.gov (United States)

    Réus, Gislaine Z; Scaini, Giselli; Titus, Stephanie E; Furlanetto, Camila B; Wessler, Leticia B; Ferreira, Gabriela K; Gonçalves, Cinara L; Jeremias, Gabriela C; Quevedo, João; Streck, Emilio L

    2015-10-01

    Methylphenidate (MPH) is the drug of choice for pharmacological treatment of attention deficit hyperactivity disorder. Studies have pointed to the role of glucose and lactate as well as in the action mechanisms of drugs used to treat these neuropsychiatric diseases. Thus, this study aims to evaluate the effects of MPH administration on lactate release and glucose uptake in the brains of young and adult rats. MPH (1.0, 2.0 and 10.0mg/kg) or saline was injected in young and adult Wistar male rats either acutely (once) or chronically (once daily for 28 days). Then, the levels of lactate release and glucose uptake were assessed in the prefrontal cortex, hippocampus, striatum, cerebellum and cerebral cortex. Chronic MPH treatment increased glucose uptake at the dose of 10.0mg/kg in the prefrontal cortex and striatum, and at the dose of 2.0mg/kg in the cerebral cortex of young rats. In adult rats, an increase in glucose uptake was observed after acute administration of MPH at the dose of 10.0mg/kg in the prefrontal cortex. After chronic treatment, there was an increase in glucose uptake with MPH doses of 2.0 and 10.0mg/kg in the prefrontal cortex, and at an MPH dose of 2.0mg/kg in the striatum of adult rats. The lactate release did not change with either acute or chronic treatments in young or adult rats. These findings indicate that MPH increases glucose consumption in the brain, and that these changes are dependent on age and posology. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  13. Changes in blood glucose among trained normoglycemic adults during a mini-trampoline exercise session.

    Science.gov (United States)

    Martins Cunha, Raphael; Raiana Bentes, Mariana; Araújo, Victor H; DA Costa Souza, Mayara C; Vasconcelos Noleto, Marcelo; Azevedo Soares, Ademar; Machado Lehnen, Alexandre

    2016-12-01

    Blood glucose changes response during and after exercise are modulated by the postabsorptive state, intensity and duration of exercise, and the level of physical fitness as well. This study focused on the idea that high-intensity interval exercise, as mini-trampoline class, can reduce blood glucose. Thus, we examined acute changes in blood glucose among trained normoglycemic adults during a mini-trampoline exercise session. Twenty-four normoglycemic adult subjects were enrolled in the study. After physical assessment they were randomly assigned to either the experimental (N.=12) or the control group (N.=12). The experimental group performed a 50-minute session of moderate-to-high intensity (70 to 85% HRmax) exercise on a mini-trampoline commonly used in fitness classes. The control group did not perform any exercise, and all procedures were otherwise similar to the experimental group. Capillary blood glucose was measured before and every 15 minutes during the exercise session. The effects of exercise on blood glucose levels (group; time; and group interaction) were estimated using a generalized estimating equation (GEE) followed by Bonferroni's post-hoc Test (Ptrampoline can be used for reducing blood glucose levels and thus can potentially control blood glucose.

  14. Contribution of Fetal, but Not Adult, Pulmonary Mesothelium to Mesenchymal Lineages in Lung Homeostasis and Fibrosis.

    Science.gov (United States)

    von Gise, Alexander; Stevens, Sean M; Honor, Leah B; Oh, Jin Hee; Gao, Chi; Zhou, Bin; Pu, William T

    2016-02-01

    The lung is enveloped by a layer of specialized epithelium, the pulmonary mesothelium. In other organs, mesothelial cells undergo epithelial-mesenchymal transition and contribute to organ stromal cells. The contribution of pulmonary mesothelial cells (PMCs) to the developing lung has been evaluated with differing conclusions. PMCs have also been indirectly implicated in lung fibrosis in the progressive, fatal lung disease idiopathic pulmonary fibrosis. We used fetal or postnatal genetic pulse labeling of PMCs to assess their fate in murine development, normal lung homeostasis, and models of pulmonary fibrosis. We found that most fetal PMC-derived mesenchymal cells (PMCDCs) expressed markers of pericytes and fibroblasts, only a small minority expressed smooth muscle markers, and none expressed endothelial cell markers. Postnatal PMCs did not contribute to lung mesenchyme during normal lung homeostasis or in models of lung fibrosis. However, fetal PMCDCs were abundant and actively proliferating within fibrotic regions in lung fibrosis models, suggesting that they actively participate in the fibrotic process. These data clarify the role of fetal and postnatal PMCDCs in lung development and disease.

  15. Resistant starch lowers postprandial glucose and leptin in overweight adults consuming a moderate-to-high-fat diet: a randomized-controlled trial.

    Science.gov (United States)

    Maziarz, Mindy Patterson; Preisendanz, Sara; Juma, Shanil; Imrhan, Victorine; Prasad, Chandan; Vijayagopal, Parakat

    2017-02-21

    High-amylose maize resistant starch type 2 (HAM-RS2) stimulates gut-derived satiety peptides and reduces adiposity in animals. Human studies have not supported these findings despite improvements in glucose homeostasis and insulin sensitivity after HAM-RS2 intake which can lower adiposity-related disease risk. The primary objective of this study was to evaluate the impact of HAM-RS2 consumption on blood glucose homeostasis in overweight, healthy adults. We also examined changes in biomarkers of satiety (glucagon-like peptide-1 [GLP-1], peptide YY [PYY], and leptin) and body composition determined by anthropometrics and dual-energy x-ray absorptiometry, dietary intake, and subjective satiety measured by a visual analogue scale following HAM-RS2 consumption. Using a randomized-controlled, parallel-arm, double-blind design, 18 overweight, healthy adults consumed either muffins enriched with 30 g HAM-RS2 (n = 11) or 0 g HAM-RS2 (control; n = 7) daily for 6 weeks. The HAM-RS2 and control muffins were similar in total calories and available carbohydrate. At baseline, total PYY concentrations were significantly higher 120 min following the consumption of study muffins in the HAM-RS2 group than control group (P = 0.043). Within the HAM-RS2 group, the area under the curve (AUC) glucose (P = 0.028), AUC leptin (P = 0.022), and postprandial 120-min leptin (P = 0.028) decreased independent of changes in body composition or overall energy intake at the end of 6 weeks. Fasting total PYY increased (P = 0.033) in the HAM-RS2 group, but changes in insulin or total GLP-1 were not observed. Mean overall change in subjective satiety score did not correlate with mean AUC biomarker changes suggesting the satiety peptides did not elicit a satiation response or change in overall total caloric intake. The metabolic response from HAM-RS2 occurred despite the habitual intake of a moderate-to-high-fat diet (mean range 34.5% to 39.4% of total calories). Consuming 30

  16. Dose-response investigation into glucose facilitation of memory performance and mood in healthy young adults.

    Science.gov (United States)

    Sünram-Lea, Sandra I; Owen, Lauren; Finnegan, Yvonne; Hu, Henglong

    2011-08-01

    It has been suggested that the memory enhancing effect of glucose follows an inverted U-shaped curve, with 25 g resulting in optimal facilitation in healthy young adults. The aim of this study was to further investigate the dose dependency of the glucose facilitation effect in this population across different memory domains and to assess moderation by interindividual differences in glucose regulation and weight. Following a double-blind, repeated measures design, 30 participants were administered drinks containing five different doses of glucose (0 g, 15 g, 25 g, 50 g, and 60 g) and were tested across a range of memory tasks. Glycaemic response and changes in mood state were assessed following drink administration. Analysis of the data showed that glucose administration did not affect mood, but significant glucose facilitation of several memory tasks was observed. However, dose-response curves differed depending on the memory task with only performance on the long-term memory tasks adhering largely to the previously observed inverted U-shaped dose-response curve. Moderation of the response profiles by interindividual differences in glucose regulation and weight was observed. The current data suggest that dose-response function and optimal dose might depend on cognitive domain and are moderated by interindividual differences in glucose regulation and weight.

  17. Subchronic effects of inhaled ambient particulate matter on glucose homeostasis and target organ damage in a type 1 diabetic rat model

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Yuan-Horng [Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Department of Medical Research, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan (China); Charles, Chou C.-K. [Research Center for Environmental Changes, Academia Sinica, Taipei, Taiwan (China); Wang, Jyh-Seng [Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan (China); Tung, Chun-Liang [Department of Pathology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan (China); Li, Ya-Ru; Lo, Kai [Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Cheng, Tsun-Jen, E-mail: tcheng@ntu.edu.tw [Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan (China)

    2014-12-01

    Epidemiological studies have reported associations between particulate matter (PM) and cardiovascular effects, and diabetes mellitus (DM) patients might be susceptible to these effects. The chief chronic injuries resulting from DM are small vascular injuries (micro-vascular complications) or large blood vessel injuries (macro-vascular complications). However, toxicological data regarding the effects of PM on DM-related cardiovascular complications is limited. Our objective was to investigate whether subchronic PM exposure alters glucose homeostasis and causes cardiovascular complications in a type 1 DM rat model. We constructed a real world PM{sub 2.5} exposure system, the Taipei Air Pollution Exposure System for Health Effects (TAPES), to continuously deliver non-concentrated PM for subchronic exposure. A type 1 DM rat model was induced using streptozotocin. Between December 22, 2009 and April 9, 2010, DM rats were exposed to PM or to filtered air (FA) using TAPES in Taipei, Taiwan, 24 h/day, 7 days/week, for a total of 16 weeks. The average concentrations (mean [SD]) of PM{sub 2.5} in the exposure and control chambers of the TAPES were 13.30 [8.65] and 0.13 [0.05] μg/m{sup 3}, respectively. Glycated hemoglobin A1c (HbA1c) was significantly elevated after exposure to PM compared with exposure to FA (mean [SD], 7.7% [3.1%] vs. 4.7% [1.0%], P < 0.05). Interleukin 6 and fibrinogen levels were significantly increased after PM exposure. PM caused focal myocarditis, aortic medial thickness, advanced glomerulosclerosis, and accentuation of tubular damage of the kidney (tubular damage index: 1.76 [0.77] vs. 1.15 [0.36], P < 0.001). PM exposure might induce the macro- and micro-vascular complications in DM through chronic hyperglycemia and systemic inflammation. - Highlights: • The study demonstrated cardiovascular and renal effects of PM in a rat model of DM. • TAPES is a continuous, real world, long-term PM exposure system. • HbA1c, a marker of glycemic

  18. Subchronic effects of inhaled ambient particulate matter on glucose homeostasis and target organ damage in a type 1 diabetic rat model

    International Nuclear Information System (INIS)

    Yan, Yuan-Horng; Charles, Chou C.-K.; Wang, Jyh-Seng; Tung, Chun-Liang; Li, Ya-Ru; Lo, Kai; Cheng, Tsun-Jen

    2014-01-01

    Epidemiological studies have reported associations between particulate matter (PM) and cardiovascular effects, and diabetes mellitus (DM) patients might be susceptible to these effects. The chief chronic injuries resulting from DM are small vascular injuries (micro-vascular complications) or large blood vessel injuries (macro-vascular complications). However, toxicological data regarding the effects of PM on DM-related cardiovascular complications is limited. Our objective was to investigate whether subchronic PM exposure alters glucose homeostasis and causes cardiovascular complications in a type 1 DM rat model. We constructed a real world PM 2.5 exposure system, the Taipei Air Pollution Exposure System for Health Effects (TAPES), to continuously deliver non-concentrated PM for subchronic exposure. A type 1 DM rat model was induced using streptozotocin. Between December 22, 2009 and April 9, 2010, DM rats were exposed to PM or to filtered air (FA) using TAPES in Taipei, Taiwan, 24 h/day, 7 days/week, for a total of 16 weeks. The average concentrations (mean [SD]) of PM 2.5 in the exposure and control chambers of the TAPES were 13.30 [8.65] and 0.13 [0.05] μg/m 3 , respectively. Glycated hemoglobin A1c (HbA1c) was significantly elevated after exposure to PM compared with exposure to FA (mean [SD], 7.7% [3.1%] vs. 4.7% [1.0%], P < 0.05). Interleukin 6 and fibrinogen levels were significantly increased after PM exposure. PM caused focal myocarditis, aortic medial thickness, advanced glomerulosclerosis, and accentuation of tubular damage of the kidney (tubular damage index: 1.76 [0.77] vs. 1.15 [0.36], P < 0.001). PM exposure might induce the macro- and micro-vascular complications in DM through chronic hyperglycemia and systemic inflammation. - Highlights: • The study demonstrated cardiovascular and renal effects of PM in a rat model of DM. • TAPES is a continuous, real world, long-term PM exposure system. • HbA1c, a marker of glycemic homeostasis, was

  19. Validity of a portable glucose, total cholesterol, and triglycerides multi-analyzer in adults.

    Science.gov (United States)

    Coqueiro, Raildo da Silva; Santos, Mateus Carmo; Neto, João de Souza Leal; Queiroz, Bruno Morbeck de; Brügger, Nelson Augusto Jardim; Barbosa, Aline Rodrigues

    2014-07-01

    This study investigated the accuracy and precision of the Accutrend Plus system to determine blood glucose, total cholesterol, and plasma triglycerides in adults and evaluated its efficiency in measuring these blood variables. The sample consisted of 53 subjects (≥ 18 years). For blood variable laboratory determination, venous blood samples were collected and processed in a Labmax 240 analyzer. To measure blood variables with the Accutrend Plus system, samples of capillary blood were collected. In the analysis, the following tests were included: Wilcoxon and Student's t-tests for paired samples, Lin's concordance coefficient, Bland-Altman method, receiver operating characteristic curve, McNemar test, and k statistics. The results show that the Accutrend Plus system provided significantly higher values (p ≤ .05) of glucose and triglycerides but not of total cholesterol (p > .05) as compared to the values determined in the laboratory. However, the system showed good reproducibility (Lin's coefficient: glucose = .958, triglycerides = .992, total cholesterol = .940) and high concordance with the laboratory method (Lin's coefficient: glucose = .952, triglycerides = .990, total cholesterol = .944) and high sensitivity (glucose = 80.0%, triglycerides = 90.5%, total cholesterol = 84.4%) and specificity (glucose = 100.0%, triglycerides = 96.9%, total cholesterol = 95.2%) in the discrimination of high values of the three blood variables analyzed. It could be concluded that despite the tendency to overestimate glucose and triglyceride levels, a portable multi-analyzer is a valid alternative for the monitoring of metabolic disorders and cardiovascular risk factors. © The Author(s) 2013.

  20. Risk Factors Associated with Elevated Blood Glucose Among Adults ...

    African Journals Online (AJOL)

    expenditure of USD 612 billion dollars in 2014 ... such as high intake of dense caloric foods, sedentary lifestyle, smoking, and limited intake of fruits ... utmost importance to intervene, and modify lifestyle behaviours of adults so ..... A systematic review Diabetes Research and clinical practice. Journal of the American Medical.

  1. Risk factors associated with elevated blood glucose among adults in ...

    African Journals Online (AJOL)

    This cross-sectional study was conducted to assess the risk factors and lifestyles characteristics associated with type 2 diabetes mellitus among adults in Mwanza city, Tanzania. A multistage random sampling technique was used to obtain 640 male and females respondents aged 30 and above years. Data were collected ...

  2. Cognitive function in adult offspring of women with gestational diabetes-the role of glucose and other factors

    DEFF Research Database (Denmark)

    Clausen, Tine D; Mortensen, Erik Lykke; Schmidt, Lone

    2013-01-01

    We aimed to evaluate cognitive function in adult offspring of women with diet-treated gestational diabetes and to study potential associations with maternal glucose values.......We aimed to evaluate cognitive function in adult offspring of women with diet-treated gestational diabetes and to study potential associations with maternal glucose values....

  3. Geographic differences in the associations between impaired glucose regulation and cardiovascular risk factors among young adults

    DEFF Research Database (Denmark)

    Oya, J.; Vistisen, D.; Christensen, Dirk Lund

    2015-01-01

    AIMS: To assess geographic differences in the association between BMI, blood pressure and lipid levels with impaired glucose regulation among young adults from various geographical regions. METHODS: This was a cross-sectional study including data from 6987 participants aged ≤ 30 years from India,...

  4. Membrane potential dye imaging of ventromedial hypothalamus neurons from adult mice to study glucose sensing.

    Science.gov (United States)

    Vazirani, Reema P; Fioramonti, Xavier; Routh, Vanessa H

    2013-11-27

    Studies of neuronal activity are often performed using neurons from rodents less than 2 months of age due to the technical difficulties associated with increasing connective tissue and decreased neuronal viability that occur with age. Here, we describe a methodology for the dissociation of healthy hypothalamic neurons from adult-aged mice. The ability to study neurons from adult-aged mice allows the use of disease models that manifest at a later age and might be more developmentally accurate for certain studies. Fluorescence imaging of dissociated neurons can be used to study the activity of a population of neurons, as opposed to using electrophysiology to study a single neuron. This is particularly useful when studying a heterogeneous neuronal population in which the desired neuronal type is rare such as for hypothalamic glucose sensing neurons. We utilized membrane potential dye imaging of adult ventromedial hypothalamic neurons to study their responses to changes in extracellular glucose. Glucose sensing neurons are believed to play a role in central regulation of energy balance. The ability to study glucose sensing in adult rodents is particularly useful since the predominance of diseases related to dysfunctional energy balance (e.g. obesity) increase with age.

  5. Perinatal exposure to perfluorooctane sulfonate affects glucose metabolism in adult offspring.

    Directory of Open Access Journals (Sweden)

    Hin T Wan

    Full Text Available Perfluoroalkyl acids (PFAAs are globally present in the environment and are widely distributed in human populations and wildlife. The chemicals are ubiquitous in human body fluids and have a long serum elimination half-life. The notorious member of PFAAs, perfluorooctane sulfonate (PFOS is prioritized as a global concerning chemical at the Stockholm Convention in 2009, due to its harmful effects in mammals and aquatic organisms. PFOS is known to affect lipid metabolism in adults and was found to be able to cross human placenta. However the effects of in utero exposure to the susceptibility of metabolic disorders in offspring have not yet been elucidated. In this study, pregnant CD-1 mice (F0 were fed with 0, 0.3 or 3 mg PFOS/kg body weight/day in corn oil by oral gavage daily throughout gestational and lactation periods. We investigated the immediate effects of perinatal exposure to PFOS on glucose metabolism in both maternal and offspring after weaning (PND 21. To determine if the perinatal exposure predisposes the risk for metabolic disorder to the offspring, weaned animals without further PFOS exposure, were fed with either standard or high-fat diet until PND 63. Fasting glucose and insulin levels were measured while HOMA-IR index and glucose AUCs were reported. Our data illustrated the first time the effects of the environmental equivalent dose of PFOS exposure on the disturbance of glucose metabolism in F1 pups and F1 adults at PND 21 and 63, respectively. Although the biological effects of PFOS on the elevated levels of fasting serum glucose and insulin levels were observed in both pups and adults of F1, the phenotypes of insulin resistance and glucose intolerance were only evident in the F1 adults. The effects were exacerbated under HFD, highlighting the synergistic action at postnatal growth on the development of metabolic disorders.

  6. The expression of dominant negative TCF7L2 in pancreatic beta cells during the embryonic stage causes impaired glucose homeostasis.

    Science.gov (United States)

    Shao, Weijuan; Xiong, Xiaoquan; Ip, Wilfred; Xu, Fenghao; Song, Zhuolun; Zeng, Kejing; Hernandez, Marcela; Liang, Tao; Weng, Jianping; Gaisano, Herbert; Nostro, M Cristina; Jin, Tianru

    2015-04-01

    Disruption of TCF7L2 in mouse pancreatic β-cells has generated different outcomes in several investigations. Here we aim to clarify role of β-cell TCF7L2 and Wnt signaling using a functional-knockdown approach. Adenovirus-mediated dominant negative TCF7L2 (TCF7L2DN) expression was conducted in Ins-1 cells. The fusion gene in which TCF7L2DN expression is driven by P TRE3G was utilized to generate the transgenic mouse line TCF7L2DN Tet . The double transgenic line was created by mating TCF7L2DN Tet with Ins2-rtTA, designated as βTCFDN. β-cell specific TCF7L2DN expression was induced in βTCFDN by doxycycline feeding. TCF7L2DN expression in Ins-1 cells reduced GSIS, cell proliferation and expression of a battery of genes including incretin receptors and β-cell transcription factors. Inducing TCF7L2DN expression in βTCFDN during adulthood or immediately after weaning generated no or very modest metabolic defect, while its expression during embryonic development by doxycycline feeding in pregnant mothers resulted in significant glucose intolerance associated with altered β-cell gene expression and reduced β-cell mass. Our observations support a cell autonomous role for TCF7L2 in pancreatic β-cells suggested by most, though not all, investigations. βTCFDN is a novel model for further exploring the role of TCF7L2 in β-cell genesis and metabolic homeostasis.

  7. High prevalence of impaired glucose homeostasis and myopathy in asymptomatic and oligosymptomatic 3243A>G mitochondrial DNA mutation-positive subjects

    DEFF Research Database (Denmark)

    Frederiksen, A.L.; Jeppesen, T.D.; Vissing, J.

    2009-01-01

    controls were subjected to an oral glucose tolerance test. Twenty-six adult 3243A>G carriers with unknown myopathy status and 17 healthy controls had a maximal cycle test and a muscle biopsy performed. The mutation loads were quantified in blood and muscle biopsies and correlated to the clinical......INTRODUCTION: The point mutation of 3243A>G mtDNA is the most frequent cause of mitochondrial diabetes, often presenting as the syndrome maternally inherited diabetes and deafness (MIDD). The mutation may also cause myopathy, ataxia, strokes, ophthalmoplegia, epilepsy, and cardiomyopathy in various...... combinations. Consequently, it is difficult to predict the "phenotypic risk profile" of 3243A>G mutation-positive subjects. The 3243A>G mutation coexists in cells with wild-type mtDNA, a phenomenon called heteroplasmy. The marked variability in mutation loads in different tissues is the main explanation...

  8. Short-term consumption of sucralose, a nonnutritive sweetener, is similar to water with regard to select markers of hunger signaling and short-term glucose homeostasis in women.

    Science.gov (United States)

    Brown, Andrew W; Bohan Brown, Michelle M; Onken, Kristine L; Beitz, Donald C

    2011-12-01

    Nonnutritive sweeteners have been used to lower the energy density of foods with the intention of affecting weight loss or weight maintenance. However, some epidemiological and animal evidence indicates an association between weight gain or insulin resistance and artificial sweetener consumption. In the present study, we hypothesized that the nonnutritive sweetener sucralose, a trichlorinated sucrose molecule, would elicit responses similar to water but different from sucrose and sucrose combined with sucralose on subjective and hormonal indications of hunger and short-term glucose homeostasis. Eight female volunteers (body mass index, 22.16 ± 1.71 kg/m(2); age, 21.75 ± 2.25 years) consumed sucrose and/or sucralose in water in a factorial design. Blood samples were taken at fasting and 30 and 60 minutes after treatment followed by a standardized breakfast across treatments, and blood samples were taken 30, 60, 90, and 120 minutes after breakfast. Plasma was analyzed for glucose, insulin, glucagon, triacylglycerols (TAG), and acylated ghrelin. Perceptions of hunger and other subjective measurements were assessed before each blood sample. No differences were detected in subjective responses, circulating triacylglycerol, or glucagon concentrations among treatments over time. Significant differences were observed in insulin, glucose, and acylated ghrelin concentrations over time only between sucrose-containing treatments and non-sucrose-containing treatments regardless of sucralose consumption. Therefore, sucralose may be a relatively inert nonnutritive sweetener with regard to hunger signaling and short-term glucose homeostasis. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Aberrant mitochondrial homeostasis in the skeletal muscle of sedentary older adults.

    Directory of Open Access Journals (Sweden)

    Adeel Safdar

    Full Text Available The role of mitochondrial dysfunction and oxidative stress has been extensively characterized in the aetiology of sarcopenia (aging-associated loss of muscle mass and muscle wasting as a result of muscle disuse. What remains less clear is whether the decline in skeletal muscle mitochondrial oxidative capacity is purely a function of the aging process or if the sedentary lifestyle of older adult subjects has confounded previous reports. The objective of the present study was to investigate if a recreationally active lifestyle in older adults can conserve skeletal muscle strength and functionality, chronic systemic inflammation, mitochondrial biogenesis and oxidative capacity, and cellular antioxidant capacity. To that end, muscle biopsies were taken from the vastus lateralis of young and age-matched recreationally active older and sedentary older men and women (N = 10/group; female symbol = male symbol. We show that a physically active lifestyle is associated with the partial compensatory preservation of mitochondrial biogenesis, and cellular oxidative and antioxidant capacity in skeletal muscle of older adults. Conversely a sedentary lifestyle, associated with osteoarthritis-mediated physical inactivity, is associated with reduced mitochondrial function, dysregulation of cellular redox status and chronic systemic inflammation that renders the skeletal muscle intracellular environment prone to reactive oxygen species-mediated toxicity. We propose that an active lifestyle is an important determinant of quality of life and molecular progression of aging in skeletal muscle of the elderly, and is a viable therapy for attenuating and/or reversing skeletal muscle strength declines and mitochondrial abnormalities associated with aging.

  10. Postprandial Glucose Surges after Extremely Low Carbohydrate Diet in Healthy Adults.

    Science.gov (United States)

    Kanamori, Koji; Ihana-Sugiyama, Noriko; Yamamoto-Honda, Ritsuko; Nakamura, Tomoka; Sobe, Chie; Kamiya, Shigemi; Kishimoto, Miyako; Kajio, Hiroshi; Kawano, Kimiko; Noda, Mitsuhiko

    2017-09-01

    Carbohydrate-restricted diets are prevalent not only in obese people but also in the general population to maintain appropriate body weight. Here, we report that extreme carbohydrate restriction for one day affects the subsequent blood glucose levels in healthy adults. Ten subjects (median age 30.5 years, BMI 21.1 kg/m 2 , and HbA1c 5.5%), wearing with a continuous glucose monitoring device, were given isoenergetic test meals for 4 consecutive days. On day 1, day 2 (D2), and day 4 (D4), they consumed normal-carbohydrate (63-66% carbohydrate) diet, while on day 3, they took low-carbohydrate/high-fat (5% carbohydrate) diet. The daily energy intake was 2,200 kcal for males and 1,700 kcal for females. On D2 and D4, we calculated the mean 24-hr blood glucose level (MEAN/24h) and its standard deviation (SD/24h), the area under the curve (AUC) for glucose over 140 mg/dL within 4 hours after each meal (AUC/4h/140), the mean amplitude of the glycemic excursions (MAGE), the incremental AUC of 24-hr blood glucose level above the mean plus one standard deviation (iAUC/MEAN+SD). Indexes for glucose fluctuation on D4 were significantly greater than those on D2 (SD/24h; p = 0.009, MAGE; p = 0.013, AUC/4h/140 after breakfast and dinner; p = 0.006 and 0.005, and iAUC/MEAN+SD; p = 0.007). The value of MEAN/24h and AUC/4h/140 after lunch on D4 were greater than those on D2, but those differences were not statistically significant. In conclusion, consumption of low-carbohydrate/high-fat diet appears to cause higher postprandial blood glucose on subsequent normal-carbohydrate diet particularly after breakfast and dinner in healthy adults.

  11. Sleep disturbances and glucose homeostasis

    NARCIS (Netherlands)

    Barf, R. Paulien; Scheurink, Anton J.W.

    2011-01-01

    Sleep disturbances, induced by either lifestyle, shift work or sleeping disorders, have become more prevalent in our 24/7 Western society. Sleep disturbances are associated with impaired health including metabolic diseases such as obesity and type 2 diabetes. The question remains whether there is a

  12. Social Inclusion Predicts Lower Blood Glucose and Low-Density Lipoproteins in Healthy Adults.

    Science.gov (United States)

    Floyd, Kory; Veksler, Alice E; McEwan, Bree; Hesse, Colin; Boren, Justin P; Dinsmore, Dana R; Pavlich, Corey A

    2017-08-01

    Loneliness has been shown to have direct effects on one's personal well-being. Specifically, a greater feeling of loneliness is associated with negative mental health outcomes, negative health behaviors, and an increased likelihood of premature mortality. Using the neuroendocrine hypothesis, we expected social inclusion to predict decreases in both blood glucose levels and low-density lipoproteins (LDLs) and increases in high-density lipoproteins (HDLs). Fifty-two healthy adults provided self-report data for social inclusion and blood samples for hematological tests. Results indicated that higher social inclusion predicted lower levels of blood glucose and LDL, but had no effect on HDL. Implications for theory and practice are discussed.

  13. Changes in blood glucose and salivary cortisol are not necessary for arousal to enhance memory in young or older adults.

    Science.gov (United States)

    Gore, Jane B; Krebs, Desiree L; Parent, Marise B

    2006-06-01

    Emotional arousal enhances memory, and this memory-enhancing effect may involve neurochemicals released by arousal, such as glucose and cortisol. Physiological consequences of arousal change with age, and these changes may contribute to age-related memory decline. The present study examined whether emotionally arousing pictures would affect glucose and cortisol levels and enhance memory in young and older adults. Blood glucose and salivary cortisol were measured once before and six times after young and old adults viewed either 60 highly arousing or 60 relatively neutral pictures. Recall for the stimuli was measured 75 min later. The results indicated that recall was impaired in older adults. Arousal as measured by self-report enhanced recall in both young and older adults. However, arousal did not affect glucose or cortisol levels in either group. These findings demonstrate that changes in blood glucose or salivary cortisol levels are not necessary for arousal to enhance memory.

  14. BAG3 regulates contractility and Ca2+ homeostasis in adult mouse ventricular myocytes

    OpenAIRE

    Feldman, Arthur M.; Gordon, Jennifer; Wang, JuFang; Song, Jianliang; Zhang, Xue-Qian; Myers, Valerie D.; Tilley, Douglas G.; Gao, Erhe; Hoffman, Nicholas E.; Tomar, Dhanendra; Madesh, Muniswamy; Rabinowitz, Joseph; Koch, Walter J.; Su, Feifei; Khalili, Kamel

    2016-01-01

    Bcl2-associated athanogene 3 (BAG3) is a 575 amino acid anti-apoptotic protein that is constitutively expressed in the heart. BAG3 mutations, including mutations leading to loss of protein, are associated with familial cardiomyopathy. Furthermore, BAG3 levels have been found to be reduced in end-stage non-familial failing myocardium. In contrast to neonatal myocytes in which BAG3 is found in the cytoplasm and involved in protein quality control and apoptosis, in adult mouse left ventricular (...

  15. Fat distribution and glucose intolerance among Greenland inuit

    DEFF Research Database (Denmark)

    Jørgensen, Marit Eika; Borch-Johnsen, Knut; Stolk, Ronald

    2013-01-01

    circumference [WC], and percentage of body fat) and the indices of glucose metabolism (fasting and 2-h glucose levels, insulin resistance per homeostasis model assessment [HOMA-IR], and the insulin sensitivity index [ISI0,120]) among Greenland Inuit. RESEARCH DESIGN AND METHODS A total of 3,108 adult Inuit...... associated with glucose intolerance, fasting and 2-h plasma glucose levels, HOMA-IR, and ISI0,120. VAT was more strongly associated with all outcomes than was SAT. After further adjustment for BMI or WC, VAT was associated with glucose intolerance and insulin resistance, whereas there was a trend toward...

  16. Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis.

    Science.gov (United States)

    Bozec, Aline; Hannemann, Nicole

    2016-06-03

    Considering that adipose tissue (AT) is an endocrine organ, it can influence whole body metabolism. Excessive energy storage leads to the dysregulation of adipocytes, which in turn induces abnormal secretion of adipokines, triggering metabolic syndromes such as obesity, dyslipidemia, hyperglycemia, hyperinsulinemia, insulin resistance and type 2 diabetes. Therefore, investigating the molecular mechanisms behind adipocyte dysregulation could help to develop novel therapeutic strategies. Our protocol describes methods for evaluating the molecular mechanism affected by hypoxic conditions of the AT, which correlates with adipocyte apoptosis in adult mice. This protocol describes how to analyze AT in vivo through gene expression profiling as well as histological analysis of adipocyte differentiation, proliferation and apoptosis during hypoxia exposure, ascertained through staining of hypoxic cells or HIF-1α protein. Furthermore, in vitro analysis of adipocyte differentiation and its responses to various stimuli completes the characterization of the molecular pathways behind possible adipocyte dysfunction leading to metabolic syndromes.

  17. Accuracy of subcutaneous continuous glucose monitoring in critically ill adults: improved sensor performance with enhanced calibrations.

    Science.gov (United States)

    Leelarathna, Lalantha; English, Shane W; Thabit, Hood; Caldwell, Karen; Allen, Janet M; Kumareswaran, Kavita; Wilinska, Malgorzata E; Nodale, Marianna; Haidar, Ahmad; Evans, Mark L; Burnstein, Rowan; Hovorka, Roman

    2014-02-01

    Accurate real-time continuous glucose measurements may improve glucose control in the critical care unit. We evaluated the accuracy of the FreeStyle(®) Navigator(®) (Abbott Diabetes Care, Alameda, CA) subcutaneous continuous glucose monitoring (CGM) device in critically ill adults using two methods of calibration. In a randomized trial, paired CGM and reference glucose (hourly arterial blood glucose [ABG]) were collected over a 48-h period from 24 adults with critical illness (mean±SD age, 60±14 years; mean±SD body mass index, 29.6±9.3 kg/m(2); mean±SD Acute Physiology and Chronic Health Evaluation score, 12±4 [range, 6-19]) and hyperglycemia. In 12 subjects, the CGM device was calibrated at variable intervals of 1-6 h using ABG. In the other 12 subjects, the sensor was calibrated according to the manufacturer's instructions (1, 2, 10, and 24 h) using arterial blood and the built-in point-of-care glucometer. In total, 1,060 CGM-ABG pairs were analyzed over the glucose range from 4.3 to 18.8 mmol/L. Using enhanced calibration median (interquartile range) every 169 (122-213) min, the absolute relative deviation was lower (7.0% [3.5, 13.0] vs. 12.8% [6.3, 21.8], P<0.001), and the percentage of points in the Clarke error grid Zone A was higher (87.8% vs. 70.2%). Accuracy of the Navigator CGM device during critical illness was comparable to that observed in non-critical care settings. Further significant improvements in accuracy may be obtained by frequent calibrations with ABG measurements.

  18. Regrowing the adult brain: NF-κB controls functional circuit formation and tissue homeostasis in the dentate gyrus.

    Directory of Open Access Journals (Sweden)

    Yvonne Imielski

    Full Text Available Cognitive decline during aging is correlated with a continuous loss of cells within the brain and especially within the hippocampus, which could be regenerated by adult neurogenesis. Here we show that genetic ablation of NF-κB resulted in severe defects in the neurogenic region (dentate gyrus of the hippocampus. Despite increased stem cell proliferation, axogenesis, synaptogenesis and neuroprotection were hampered, leading to disruption of the mossy fiber pathway and to atrophy of the dentate gyrus during aging. Here, NF-κB controls the transcription of FOXO1 and PKA, regulating axogenesis. Structural defects culminated in behavioral impairments in pattern separation. Re-activation of NF-κB resulted in integration of newborn neurons, finally to regeneration of the dentate gyrus, accompanied by a complete recovery of structural and behavioral defects. These data identify NF-κB as a crucial regulator of dentate gyrus tissue homeostasis suggesting NF-κB to be a therapeutic target for treating cognitive and mood disorders.

  19. Regrowing the Adult Brain: NF-κB Controls Functional Circuit Formation and Tissue Homeostasis in the Dentate Gyrus

    Science.gov (United States)

    Imielski, Yvonne; Schwamborn, Jens C.; Lüningschrör, Patrick; Heimann, Peter; Holzberg, Magdalena; Werner, Hendrikje; Leske, Oliver; Püschel, Andreas W.; Memet, Sylvie; Heumann, Rolf; Israel, Alain; Kaltschmidt, Christian; Kaltschmidt, Barbara

    2012-01-01

    Cognitive decline during aging is correlated with a continuous loss of cells within the brain and especially within the hippocampus, which could be regenerated by adult neurogenesis. Here we show that genetic ablation of NF-κB resulted in severe defects in the neurogenic region (dentate gyrus) of the hippocampus. Despite increased stem cell proliferation, axogenesis, synaptogenesis and neuroprotection were hampered, leading to disruption of the mossy fiber pathway and to atrophy of the dentate gyrus during aging. Here, NF-κB controls the transcription of FOXO1 and PKA, regulating axogenesis. Structural defects culminated in behavioral impairments in pattern separation. Re-activation of NF-κB resulted in integration of newborn neurons, finally to regeneration of the dentate gyrus, accompanied by a complete recovery of structural and behavioral defects. These data identify NF-κB as a crucial regulator of dentate gyrus tissue homeostasis suggesting NF-κB to be a therapeutic target for treating cognitive and mood disorders. PMID:22312433

  20. BAG3 regulates contractility and Ca(2+) homeostasis in adult mouse ventricular myocytes.

    Science.gov (United States)

    Feldman, Arthur M; Gordon, Jennifer; Wang, JuFang; Song, Jianliang; Zhang, Xue-Qian; Myers, Valerie D; Tilley, Douglas G; Gao, Erhe; Hoffman, Nicholas E; Tomar, Dhanendra; Madesh, Muniswamy; Rabinowitz, Joseph; Koch, Walter J; Su, Feifei; Khalili, Kamel; Cheung, Joseph Y

    2016-03-01

    Bcl2-associated athanogene 3 (BAG3) is a 575 amino acid anti-apoptotic protein that is constitutively expressed in the heart. BAG3 mutations, including mutations leading to loss of protein, are associated with familial cardiomyopathy. Furthermore, BAG3 levels have been found to be reduced in end-stage non-familial failing myocardium. In contrast to neonatal myocytes in which BAG3 is found in the cytoplasm and involved in protein quality control and apoptosis, in adult mouse left ventricular (LV) myocytes BAG3 co-localized with Na(+)-K(+)-ATPase and L-type Ca(2+) channels in the sarcolemma and t-tubules. BAG3 co-immunoprecipitated with β1-adrenergic receptor, L-type Ca(2+) channels and phospholemman. To simulate decreased BAG3 protein levels observed in human heart failure, we targeted BAG3 by shRNA (shBAG3) in adult LV myocytes. Reducing BAG3 by 55% resulted in reduced contraction and [Ca(2+)]i transient amplitudes in LV myocytes stimulated with isoproterenol. L-type Ca(2+) current (ICa) and sarcoplasmic reticulum (SR) Ca(2+) content but not Na(+)/Ca(2+) exchange current (INaCa) or SR Ca(2+) uptake were reduced in isoproterenol-treated shBAG3 myocytes. Forskolin or dibutyryl cAMP restored ICa amplitude in shBAG3 myocytes to that observed in WT myocytes, consistent with BAG3 having effects upstream and at the level of the receptor. Resting membrane potential and action potential amplitude were unaffected but APD50 and APD90 were prolonged in shBAG3 myocytes. Protein levels of Ca(2+) entry molecules and other important excitation-contraction proteins were unchanged in myocytes with lower BAG3. Our findings that BAG3 is localized at the sarcolemma and t-tubules while modulating myocyte contraction and action potential duration through specific interaction with the β1-adrenergic receptor and L-type Ca(2+) channel provide novel insight into the role of BAG3 in cardiomyopathies and increased arrhythmia risks in heart failure. Copyright © 2016 Elsevier Ltd. All rights

  1. BAG3 regulates contractility and Ca2+ homeostasis in adult mouse ventricular myocytes

    Science.gov (United States)

    Feldman, Arthur M.; Gordon, Jennifer; Wang, JuFang; Song, Jianliang; Zhang, Xue-Qian; Myers, Valerie D.; Tilley, Douglas G.; Gao, Erhe; Hoffman, Nicholas E.; Tomar, Dhanendra; Madesh, Muniswamy; Rabinowitz, Joseph; Koch, Walter J.; Su, Feifei; Khalili, Kamel; Cheung, Joseph Y.

    2016-01-01

    Bcl2-associated athanogene 3 (BAG3) is a 575 amino acid anti-apoptotic protein that is constitutively expressed in the heart. BAG3 mutations, including mutations leading to loss of protein, are associated with familial cardiomyopathy. Furthermore, BAG3 levels have been found to be reduced in end-stage non-familial failing myocardium. In contrast to neonatal myocytes in which BAG3 is found in the cytoplasm and involved in protein quality control and apoptosis, in adult mouse left ventricular (LV) myocytes BAG3 co-localized with Na+-K+-ATPase and L-type Ca2+ channels in the sarcolemma and t-tubules. BAG3 co-immunoprecipitated with β1-adrenergic receptor, L-type Ca2+ channels and phospholemman. To simulate decreased BAG3 protein levels observed in human heart failure, we targeted BAG3 by shRNA (shBAG3) in adult LV myocytes. Reducing BAG3 by 55% resulted in reduced contraction and [Ca2+]i transient amplitudes in LV myocytes stimulated with isoproterenol. L-type Ca2+ current (ICa) and sarcoplasmic reticulum (SR) Ca2+ content but not Na+/Ca2+ exchange current (INaCa) or SR Ca2+ uptake were reduced in isoproterenol-treated shBAG3 myocytes. Forskolin or dibutyrl cAMP restored ICa amplitude in shBAG3 myocytes to that observed in WT myocytes, consistent with BAG3 having effects upstream and at the level of the receptor. Resting membrane potential and action potential amplitude were unaffected but APD50 and APD90 were prolonged in shBAG3 myocytes. Protein levels of Ca2+ entry molecules and other important excitation-contraction proteins were unchanged in myocytes with lower BAG3. Our findings that BAG3 is localized at the sarcolemma and t-tubules while modulating myocyte contraction and action potential duration through specific interaction with the β1-adrenergic receptor and L-type Ca2+ channel provide novel insight into the role of BAG3 in cardiomyopathies and increased arrhythmia risks in heart failure. PMID:26796036

  2. comparative study of glucose homeostasis, lipids and lipoproteins, HDL functionality, and cardiometabolic parameters in modestly severely obese African Americans and White Americans with prediabetes: implications for the metabolic paradoxes.

    Science.gov (United States)

    Healy, Sara J; Osei, Kwame; Gaillard, Trudy

    2015-02-01

    To determine whether modestly severe obesity modifies glucose homeostasis, levels of cardiometabolic markers, and HDL function in African Americans (AAs) and white Americans (WAs) with prediabetes. We studied 145 subjects with prediabetes (N = 61 WAs, N = 84 AAs, mean age 46.5 ± 11.2 years, mean BMI 37.8 ± 6.3 kg/m(2)). We measured fasting levels of lipids, lipoproteins, and an inflammatory marker (C-reactive protein [CRP]); HDL functionality (i.e., levels of paraoxonase 1 [PON1]); and levels of oxidized LDL, adiponectin, and interleukin-6 (IL-6). We measured serum levels of glucose, insulin, and C-peptide during an oral glucose tolerance test. Values for insulin sensitivity index (Si), glucose effectiveness index (Sg), glucose effectiveness at zero insulin (GEZI), and acute insulin response to glucose (AIRg) were derived using a frequently sampled intravenous glucose tolerance test (using MINMOD software). Mean levels of fasting and incremental serum glucose, insulin, and C-peptide tended to be higher in WAs versus AAs. The mean Si was not different in WAs versus AAs (2.6 ± 2.3 vs. 2.9 ± 3.0 × 10(-4) × min(-1) [μU/mL](-1)). Mean values for AIRg and disposition index as well as Sg and GEZI were lower in WAs than AAs. WAs had higher serum triglyceride levels than AAs (116.1 ± 55.5 vs. 82.7 ± 44.2 mg/dL, P = 0.0002). Mean levels of apolipoprotein (apo) A1, HDL cholesterol, PON1, oxidized LDL, CRP, adiponectin, and IL-6 were not significantly different in obese AAs versus WAs with prediabetes. Modestly severe obesity attenuated the ethnic differences in Si, but not in Sg and triglyceride levels in WAs and AAs with prediabetes. Despite the lower Si and PON1 values, AAs preserved paradoxical relationships between the Si and HDL/apoA1/triglyceride ratios. We conclude that modestly severe obesity has differential effects on the pathogenic mechanisms underlying glucose homeostasis and atherogenesis in obese AAs and WAs with prediabetes. © 2015 by the American

  3. Aronia juice suppresses the elevation of postprandial blood glucose levels in adult healthy Japanese

    Directory of Open Access Journals (Sweden)

    Takuya Yamane

    2017-04-01

    Full Text Available Aronia has various functions toward human health, including the beneficial effect on hypertension, hyperglycemia and hyperlipidemia. Recently, we identified cyanidin-3,5-O-diglucoside as DPP IV inhibitor from Aronia juice. We also found its beneficial effect on hyperglycemia in KKAy mice fed aronia juice. In this study, to examine the effect of aronia juice on postprandial blood glucose levels in Japanese, we performed an oral meal tolerance test (OMTT. We found that postprandial blood glucose levels were reduced in aronia juice-administered adult healthy Japanese. We also found that there was no difference of reduction levels of postprandial blood glucose between male and female. We also found that activities of dipeptidyl peptidase IV (DPP IV, α-glucosidase and angiotensin-converting enzyme (ACE were reduced by aronia juice. These results suggest that aronia juice suppresses the elevation of postprandial blood glucose levels through inhibition of these enzyme activities and may be useful for prevention of metabolic diseases in adult healthy Japanese.

  4. Glucose transporters GLUT4 and GLUT8 are upregulated after facial nerve axotomy in adult mice.

    Science.gov (United States)

    Gómez, Olga; Ballester-Lurbe, Begoña; Mesonero, José E; Terrado, José

    2011-10-01

    Peripheral nerve axotomy in adult mice elicits a complex response that includes increased glucose uptake in regenerating nerve cells. This work analyses the expression of the neuronal glucose transporters GLUT3, GLUT4 and GLUT8 in the facial nucleus of adult mice during the first days after facial nerve axotomy. Our results show that whereas GLUT3 levels do not vary, GLUT4 and GLUT8 immunoreactivity increases in the cell body of the injured motoneurons after the lesion. A sharp increase in GLUT4 immunoreactivity was detected 3 days after the nerve injury and levels remained high on Day 8, but to a lesser extent. GLUT8 also increased the levels but later than GLUT4, as they only rose on Day 8 post-lesion. These results indicate that glucose transport is activated in regenerating motoneurons and that GLUT4 plays a main role in this function. These results also suggest that metabolic defects involving impairment of glucose transporters may be principal components of the neurotoxic mechanisms leading to motoneuron death. © 2011 The Authors. Journal of Anatomy © 2011 Anatomical Society of Great Britain and Ireland.

  5. Correlation between the Plasma Insulin and Glucose Concentration in Normal Korean Adults

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jang Kyu; Sung, Ho Kyung; Kim, Jin Eui [Radiological Research Institute, Seoul (Korea, Republic of)

    1971-09-15

    The correlation between the plasma insulin, and glucose concentration was studied in healthy Korean adults consisting of 20 males and 22 females of 16 to 38 years of age. The blood samples of above subjects were obtained through cubital vein at arbitrary times during their usual working hours. Plasma insulin was assayed by means of double antibody system of radioimmunoassay technics, and blood glucose was determined by means of Van Slyke-Folch method. Results were as follows : 1. There were no differences in the blood sugar levels in relation to the plasma insulin concentration either by sex or age. 2. In the case, when the plasma insulin concentration was within 50 mmuU/ml, the correlation between the insulin, and glucose concentration existed, the ratio of which was expressed as; Plasma glucose concentration (mg/dl)=91.9 + 0.08 X Insulin concentration r=0.62. 3. Insulinogenic index was 12.4%, which was somewhat higher than other reports. 4. It is suggested that the correlation between plasma insulin and glucose concentration could be determined at arbitrary times instead of fasting times.

  6. Changes in blood glucose and insulin responses to intravenous glucose tolerance tests and blood biochemical values in adult female Japanese black bears (Ursus thibetanus japonicus).

    Science.gov (United States)

    Kamine, Akari; Shimozuru, Michito; Shibata, Haruki; Tsubota, Toshio

    2012-02-01

    The metabolic mechanisms to circannual changes in body mass of bears have yet to be elucidated. We hypothesized that the Japanese black bear (Ursus thibetanus japonicus) has a metabolic mechanism that efficiently converts carbohydrates into body fat by altering insulin sensitivity during the hyperphagic stage before hibernation. To test this hypothesis, we investigated the changes in blood biochemical values and glucose and insulin responses to intravenous glucose tolerance tests (IVGTT) during the active season (August, early and late November). Four, adult, female bears (5-17 years old) were anesthetized with 6 mg/kg TZ (tiletamine HCl and zolazepam HCl) in combination with 0.1 mg/kg acepromazine maleate. The bears were injected intravenously with glucose (0.5 g/kg of body mass), and blood samples were obtained before, at, and intermittently after glucose injection. The basal triglycerides concentration decreased significantly with increase in body mass from August to November. Basal levels of plasma glucose and serum insulin concentrations were not significantly different among groups. The results of IVGTT demonstrated the increased peripheral insulin sensitivity and glucose tolerance in early November. In contrast, peripheral insulin resistance was indicated by the exaggerated insulin response in late November. Our findings suggest that bears shift their glucose and lipid metabolism from the stage of normal activity to the hyperphagic stage in which they show lipogenic-predominant metabolism and accelerate glucose uptake by increasing the peripheral insulin sensitivity.

  7. Circulating Spexin Levels Negatively Correlate With Age, BMI, Fasting Glucose, and Triglycerides in Healthy Adult Women.

    Science.gov (United States)

    Lin, Cheng-Yuan; Huang, Tao; Zhao, Ling; Zhong, Linda L D; Lam, Wai Ching; Fan, Bao-Min; Bian, Zhao-Xiang

    2018-05-01

    Spexin is a newly identified neuropeptide that is involved in satiety control, glucose, and lipids metabolism. It has also been related to human diseases, such as obesity and type 2 diabetes. However, whether spexin changes with age or not is still unclear. The aim of this study is to investigate the relationship between circulating spexin levels and age and to study their interaction effects on body mass index (BMI), fasting glucose, and -lipids. This is a cross-sectional study, including 68 healthy adult women whose ages are in a wide range (minimum: 23; median: 38.5; maximum: 64). The serum spexin levels were measured by an enzyme-linked immunosorbent assay. Fasting glucose, total cholesterol, triglycerides (TG), alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea, and creatinine were measured by routine biochemical test. Shapiro-Wilk's test, Spearman and Pearson correlation analyses, χ 2 test, and two-way analysis of variance were used to interpret the data. Serum spexin levels are significantly correlated with age (Spearman r = -0.277, P = 0.022), BMI (Spearman r = -0.445, P glucose (Spearman r = -0.302, P = 0.014), and TG (Spearman r = -0.324, P = 0.008). Spexin levels independently predict the risk of high BMI and high fasting glucose. No interaction effects of spexin and age on BMI and fasting glucose were found. Circulating spexin levels decrease with age, suggesting a possible role of this peptide in aging-related functions and disorders. Further investigations are needed to expand the clinical significance of this finding.

  8. Effects of Higher Dietary Protein and Fiber Intakes at Breakfast on Postprandial Glucose, Insulin, and 24-h Interstitial Glucose in Overweight Adults.

    Science.gov (United States)

    Amankwaah, Akua F; Sayer, R Drew; Wright, Amy J; Chen, Ningning; McCrory, Megan A; Campbell, Wayne W

    2017-04-02

    Dietary protein and fiber independently influence insulin-mediated glucose control. However, potential additive effects are not well-known. Men and women ( n = 20; age: 26 ± 5 years; body mass index: 26.1 ± 0.2 kg/m²; mean ± standard deviation) consumed normal protein and fiber (NPNF; NP = 12.5 g, NF = 2 g), normal protein and high fiber (NPHF; NP = 12.5 g, HF = 8 g), high protein and normal fiber (HPNF; HP = 25 g, NF = 2 g), or high protein and fiber (HPHF; HP = 25 g, HF = 8 g) breakfast treatments during four 2-week interventions in a randomized crossover fashion. On the last day of each intervention, meal tolerance tests were completed to assess postprandial (every 60 min for 240 min) serum glucose and insulin concentrations. Continuous glucose monitoring was used to measure 24-h interstitial glucose during five days of the second week of each intervention. Repeated-measures ANOVA was applied for data analyses. The HPHF treatment did not affect postprandial glucose and insulin responses or 24-h glucose total area under the curve (AUC). Higher fiber intake reduced 240-min insulin AUC. Doubling the amount of protein from 12.5 g to 25 g/meal and quadrupling fiber from 2 to 8 g/meal at breakfast was not an effective strategy for modulating insulin-mediated glucose responses in these young, overweight adults.

  9. Are barriers to physical activity similar for adults with and without abnormal glucose metabolism?

    Science.gov (United States)

    Hume, Clare; Dunstan, David; Salmon, Jo; Healy, Genevieve; Andrianopoulos, Nick; Owen, Neville

    2010-01-01

    The purpose of this study was to examine perceived barriers to physical activity among adults with and without abnormal glucose metabolism (AGM), and whether barriers varied according to physical activity status. The 1999 to 2000 Australian Diabetes, Obesity, and Lifestyle Study (AusDiab) was a population-based cross-sectional study among adults aged > or =25 years. AGM was identified through an oral glucose tolerance test. The previous week's physical activity and individual, social, and environmental barriers to physical activity were self-reported. Logistic regression analyses examined differences in barriers to physical activity between those with and without AGM, and for those with and without AGM who did and did not meet the minimum recommendation of 150 minutes/week of moderate-to-vigorous intensity physical activity. Of the 7088 participants (47.5 +/- 12.7 years; 46% male), 18.5% had AGM. Approximately 47.5% of those with AGM met the physical activity recommendation, compared to 54.7% of those without AGM (P barriers to physical activity included lack of time, other priorities, and being tired. Following adjustment for sociodemographic and behavioral factors, there were few differences in barriers to physical activity between those with and without AGM, even after stratifying according to physical activity. Adults with AGM report similar barriers to physical activity, as do those without AGM. Programs for those with AGM can therefore focus on the known generic adult-reported barriers to physical activity.

  10. Effects of hypoglycaemia on neuronal metabolism in the adult brain: role of alternative substrates to glucose.

    Science.gov (United States)

    Amaral, Ana I

    2013-07-01

    Hypoglycaemia is characterized by decreased blood glucose levels and is associated with different pathologies (e.g. diabetes, inborn errors of metabolism). Depending on its severity, it might affect cognitive functions, including impaired judgment and decreased memory capacity, which have been linked to alterations of brain energy metabolism. Glucose is the major cerebral energy substrate in the adult brain and supports the complex metabolic interactions between neurons and astrocytes, which are essential for synaptic activity. Therefore, hypoglycaemia disturbs cerebral metabolism and, consequently, neuronal function. Despite the high vulnerability of neurons to hypoglycaemia, important neurochemical changes enabling these cells to prolong their resistance to hypoglycaemia have been described. This review aims at providing an overview over the main metabolic effects of hypoglycaemia on neurons, covering in vitro and in vivo findings. Recent studies provided evidence that non-glucose substrates including pyruvate, glycogen, ketone bodies, glutamate, glutamine, and aspartate, are metabolized by neurons in the absence of glucose and contribute to prolong neuronal function and delay ATP depletion during hypoglycaemia. One of the pathways likely implicated in the process is the pyruvate recycling pathway, which allows for the full oxidation of glutamate and glutamine. The operation of this pathway in neurons, particularly after hypoglycaemia, has been re-confirmed recently using metabolic modelling tools (i.e. Metabolic Flux Analysis), which allow for a detailed investigation of cellular metabolism in cultured cells. Overall, the knowledge summarized herein might be used for the development of potential therapies targeting neuronal protection in patients vulnerable to hypoglycaemic episodes.

  11. Radiation absorbed dose estimates for [1-carbon-11]-glucose in adults: The effects of hyperinsulinemia

    International Nuclear Information System (INIS)

    Powers, W.J.

    1996-01-01

    As preparation for studies of blood-brain glucose transport in diabetes mellitus, radiation absorbed dose estimates from intravenous administration of [1- 11 C]-glucose for 24 internal organs, lens, blood and total body were calculated for three physiologic conditions: euinsulinemic euglycemia, hyperinsulinemic euglycemia and hyperinsulinemic hyperglycemia. Cumulated activities in blood, insulin-independent and insulin-dependent compartments were calculated from blood time-activity curves in normal human volunteers and macaques. Apportionment of cumulated activity to individual organs in insulin-dependent and insulin-independent compartments was based on previously published data. Absorbed doses were calculated with the computer program MIRDOSE 3 for the 70-kg adult phantom. S for blood was calculated separately. The heart wall, lungs and spleen were the organs receiving the highest dose. The effect of hyperinsulinemia was demonstrated by the increase in adsorbed dose to the muscle, heart and blood with a decrease to other internal organs. This effect was more pronounced during hyperinsulinemic hyperglycemia. Hyperinsulinemia produced a decrease in effective dose due to the decrease in cumulated activity in organs with specified weighting factors greater than 0.05. The effective dose per study for [1- 11 C]-glucose is comparable to that reported for 2-deoxy-[2- 18 F]-glucose. 43 refs., 1 fig., 4 tabs

  12. Decreased regional cerebral glucose metabolism in the prefrontal regions in adults' with internet game addiction

    International Nuclear Information System (INIS)

    Park, Hyun Soo; Bang, Soong Ae; Yoon, Eun Jin; Cho, Sang Soo; Kim, Sang Hee; Kim, Yu Kyeong; Kim, Sang Eun

    2007-01-01

    Internet Game Addiction (IGA) is known to be associated with poor decision-making and diminished impulse control; however, the underlying neural substrates of IGA have not been identified. To investigate the neural substrates of IGA, we compared regional cerebral glucose metabolism between adults with and without IGA, primarily in the prefrontal brain regions, which have been implicated in inhibitory control. We studied 10 right-handed participants (5 controls: male, 23.8±0.75 y, 5 IGAs: male, 22.6±2.42 y) with FDG PET. A standardized questionnaire was used to assess the severity of IGA. Before scanning, all subjects carried out a computerized version of the Iowa Gambling Task (IGT) and the Balloon Analogue Risk Task (BART), as measures of behavioral inhibitory control. Statistical Parametric Mapping 2 (SPM2) was used to analyze differences in regional brain glucose metabolism between adults with and without IGA. Consistent with our predictions, compared to controls, significant reductions in FDG uptake in individuals with IGA were found in the bilateral orbitofrontal gyrus (BA 11, 47), bilateral inferior frontal gyrus (BA 44, 48), cingulate cortex (BA 24), and bilateral supplementary motor area (SMA) (BA 6); whereas increases were found in the bilateral hippocampus. Correlation analyses within the IGA group further showed that the level of glucose metabolism in the right orbitofrontal gyrus was marginally positively correlated with task scores in BART. Our results showed that IGA is associated with reduced glucose metabolism in the prefrontal regions involved in inhibitory control. This finding highlights dysfunctional inhibitory brain systems in individuals with IGA and offers implications for the development for therapeutic paradigms for IGA

  13. The expression of dominant negative TCF7L2 in pancreatic beta cells during the embryonic stage causes impaired glucose homeostasis

    Directory of Open Access Journals (Sweden)

    Weijuan Shao

    2015-04-01

    Conclusions: Our observations support a cell autonomous role for TCF7L2 in pancreatic β-cells suggested by most, though not all, investigations. βTCFDN is a novel model for further exploring the role of TCF7L2 in β-cell genesis and metabolic homeostasis.

  14. Neuronal regulation of homeostasis by nutrient sensing.

    Science.gov (United States)

    Lam, Tony K T

    2010-04-01

    In type 2 diabetes and obesity, the homeostatic control of glucose and energy balance is impaired, leading to hyperglycemia and hyperphagia. Recent studies indicate that nutrient-sensing mechanisms in the body activate negative-feedback systems to regulate energy and glucose homeostasis through a neuronal network. Direct metabolic signaling within the intestine activates gut-brain and gut-brain-liver axes to regulate energy and glucose homeostasis, respectively. In parallel, direct metabolism of nutrients within the hypothalamus regulates food intake and blood glucose levels. These findings highlight the importance of the central nervous system in mediating the ability of nutrient sensing to maintain homeostasis. Futhermore, they provide a physiological and neuronal framework by which enhancing or restoring nutrient sensing in the intestine and the brain could normalize energy and glucose homeostasis in diabetes and obesity.

  15. Evaluation of the Genetic and Nutritional Control of Obesity and Type 2 Diabetes in a Novel Mouse Model on Chromosome 7: An Insight into Insulin Signaling and Glucose Homeostasis

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, S.; Dhar, M.

    2003-01-01

    Obesity is the main cause of type 2 diabetes, accounting for 90-95% of all diabetes cases in the US. Human obesity is a complex trait and can be studied using appropriate mouse models. A novel polygenic mouse model for studying the genetic and environmental contributions to and the physiological ramifications of obesity and related phenotypes is found in specific lines of mice bred and maintained at Oak Ridge National Laboratory. Heterozygous mice with a maternally inherited copy of two radiation-induced deletions in the p region of mouse chromosome 7, p23DFioD and p30PUb, have significantly greater body fat and show hyperinsulinemia compared to the wild-type. A single gene, Atp10c, maps to this critical region and codes for a putative aminophospholipid translocase. Biochemical and molecular studies were initiated to gain insight into obesity and glucose homeostasis in these animals and to study the biological role of Atp10c in creating these phenotypes. Glucose and insulin tolerance tests were standardized for the heterozygous p23DFioD and control mice on a custom-made diet containing 20% protein, 70% carbohydrate, and 10% fat (kcal). Atp10c expression profiles were also generated using Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR). Heterozygous p23DFioD animals showed insulin resistance after receiving a dose of either 0.375 or 0.75 U/kg Illetin R insulin. RT-PCR data also shows differences in Atp10c expression in the mutants versus control mice. Using these standardized biochemical assays, future studies will further the understanding of genetic and nutritional controls of glucose homeostasis and obesity in animal models and subsequently in human populations.

  16. Comparison of the effect of multiple short-duration with single long-duration exercise sessions on glucose homeostasis in type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Eriksen, L; Dahl-Petersen, I; Haugaard, Steen B

    2007-01-01

    AIMS/HYPOTHESIS: We evaluated and compared the effects on glycaemic control of two different exercise protocols in elderly men with type 2 diabetes mellitus. METHODS: Eighteen patients with type 2 diabetes mellitus carried out home-based bicycle training for 5 weeks. Patients were randomly assigned...... to one of two training programmes at 60% of maximal oxygen uptake: three 10 min sessions per day (3 x 10) or one 30 min session per day (1 x 30). Plasma insulin, C-peptide and glucose concentrations were measured during a 3 h oral glucose tolerance test (OGTT). Insulin sensitivity index (ISI......(composite)), pre-hepatic insulin secretion rates (ISR) and change in insulin secretion per unit change in glucose concentrations (B(total)) were calculated. RESULTS: Cardiorespiratory fitness increased in response to training in both groups. In group 3 x 10 (n = 9) fasting plasma glucose (p = 0.01), 120 min...

  17. Preservation of blood glucose homeostasis in slow-senescing somatotrophism-deficient mice subjected to intermittent fasting begun at middle or old age.

    Science.gov (United States)

    Arum, Oge; Saleh, Jamal K; Boparai, Ravneet K; Kopchick, John J; Khardori, Romesh K; Bartke, Andrzej

    2014-06-01

    Poor blood glucose homeostatic regulation is common, consequential, and costly for older and elderly populations, resulting in pleiotrophically adverse clinical outcomes. Somatotrophic signaling deficiency and dietary restriction have each been shown to delay the rate of senescence, resulting in salubrious phenotypes such as increased survivorship. Using two growth hormone (GH) signaling-related, slow-aging mouse mutants we tested, via longitudinal analyses, whether genetic perturbations that increase survivorship also improve blood glucose homeostatic regulation in senescing mammals. Furthermore, we institute a dietary restriction paradigm that also decelerates aging, an intermittent fasting (IF) feeding schedule, as either a short-term or a sustained intervention beginning at either middle or old age, and assess its effects on blood glucose control. We find that either of the two genetic alterations in GH signaling ameliorates fasting hyperglycemia; additionally, both longevity-inducing somatotrophic mutations improve insulin sensitivity into old age. Strikingly, we observe major and broad improvements in blood glucose homeostatic control by IF: IF improves ad libitum-fed hyperglycemia, glucose tolerance, and insulin sensitivity, and reduces hepatic gluconeogenesis, in aging mutant and normal mice. These results on correction of aging-resultant blood glucose dysregulation have potentially important clinical and public health implications for our ever-graying global population, and are consistent with the Longevity Dividend concept.

  18. Effects of resveratrol on memory performance, hippocampal functional connectivity, and glucose metabolism in healthy older adults.

    Science.gov (United States)

    Witte, A Veronica; Kerti, Lucia; Margulies, Daniel S; Flöel, Agnes

    2014-06-04

    Dietary habits such as caloric restriction or nutrients that mimic these effects may exert beneficial effects on brain aging. The plant-derived polyphenol resveratrol has been shown to increase memory performance in primates; however, interventional studies in older humans are lacking. Here, we tested whether supplementation of resveratrol would enhance memory performance in older adults and addressed potential mechanisms underlying this effect. Twenty-three healthy overweight older individuals that successfully completed 26 weeks of resveratrol intake (200 mg/d) were pairwise matched to 23 participants that received placebo (total n = 46, 18 females, 50-75 years). Before and after the intervention/control period, subjects underwent memory tasks and neuroimaging to assess volume, microstructure, and functional connectivity (FC) of the hippocampus, a key region implicated in memory functions. In addition, anthropometry, glucose and lipid metabolism, inflammation, neurotrophic factors, and vascular parameters were assayed. We observed a significant effect of resveratrol on retention of words over 30 min compared with placebo (p = 0.038). In addition, resveratrol led to significant increases in hippocampal FC, decreases in glycated hemoglobin (HbA1c) and body fat, and increases in leptin compared with placebo (all p memory performance in association with improved glucose metabolism and increased hippocampal FC in older adults. Our findings offer the basis for novel strategies to maintain brain health during aging. Copyright © 2014 the authors 0270-6474/14/347862-09$15.00/0.

  19. Self-monitoring of blood glucose experiences of adults with type 2 diabetes.

    Science.gov (United States)

    Dlugasch, Lucie B; Ugarriza, Doris N

    2014-06-01

    The purpose of this study was to analyze the experiences of self-monitoring of blood glucose (SMBG) usage of adults with type 2 diabetes mellitus (T2DM) who are not using insulin. Nineteen adults were asked to describe their experiences with self-monitoring. Data were analyzed using the grounded theory method. The theory of "SMBG as a Cue in T2DM Self-Care" emerged from the data and is composed of four categories: (a) Engaging, (b) Checking, (c) Responding, and (d) Establishing a Pattern. Engaging marks the beginning. Frequent monitoring characterizes this stage. Checking involves evaluating and validating the blood glucose level. The most common item evaluated or validated was the effect of foods. Responding involves taking action or experiencing emotion. Actions taken centered on dietary changes. Emotions felt were dependent on the level and ranged from blame to happiness. Participants established a pattern and used SMBG regularly or sporadically. Frequency was based on obtaining "normal" patterns, the absence of symptoms, provider disinterest, and fingertip pain. Participants described many benefits and struggles when incorporating SMBG into their self-care. Information from this study could be used to develop effective guidelines for the use of SMBG in T2DM. ©2013 The Author(s) ©2013 American Association of Nurse Practitioners.

  20. Three-component homeostasis control

    Science.gov (United States)

    Xu, Jin; Hong, Hyunsuk; Jo, Junghyo

    2014-03-01

    Two reciprocal components seem to be sufficient to maintain a control variable constant. However, pancreatic islets adapt three components to control glucose homeostasis. They are α (secreting glucagon), β (insulin), and δ (somatostatin) cells. Glucagon and insulin are the reciprocal hormones for increasing and decreasing blood glucose levels, while the role of somatostatin is unknown. However, it has been known how each hormone affects other cell types. Based on the pulsatile hormone secretion and the cellular interactions, this system can be described as coupled oscillators. In particular, we used the Landau-Stuart model to consider both amplitudes and phases of hormone oscillations. We found that the presence of the third component, δ cell, was effective to resist under glucose perturbations, and to quickly return to the normal glucose level once perturbed. Our analysis suggested that three components are necessary for advanced homeostasis control.

  1. Associations among the plasma amino acid profile, obesity, and glucose metabolism in Japanese adults with normal glucose tolerance

    OpenAIRE

    Takashina, Chisa; Tsujino, Ichizo; Watanabe, Taku; Sakaue, Shinji; Ikeda, Daisuke; Yamada, Asuka; Sato, Takahiro; Ohira, Hiroshi; Otsuka, Yoshinori; Oyama-Manabe, Noriko; Ito, Yoichi M.; Nishimura, Masaharu

    2016-01-01

    Background Amino acids (AAs) are emerging as a new class of effective molecules in the etiology of obesity and diabetes mellitus. However, most investigations have focused on subjects with obesity and/or impaired glucose regulation; the possible involvement of AAs in the initial phase of glucose dysregulation remains poorly understood. Furthermore, little attention has been given to possible associations between the pattern/degree of fat deposition and the plasma AA profile. Our objective was...

  2. A randomised study on the effects of fish protein supplement on glucose tolerance, lipids and body composition in overweight adults.

    Science.gov (United States)

    Vikøren, Linn A; Nygård, Ottar K; Lied, Einar; Rostrup, Espen; Gudbrandsen, Oddrun A

    2013-02-28

    The popularity of high-protein diets for weight reduction is immense. However, the potential benefits from altering the source of dietary protein rather than the amount is scarcely investigated. In the present study, we examined the effects of fish protein supplement on glucose and lipid metabolism in overweight adults. A total of thirty-four overweight adults were randomised to 8 weeks' supplementation with fish protein or placebo tablets (controls). The intake of fish protein supplement was 3 g/d for the first 4 weeks and 6 g/d for the last 4 weeks. In this study, 8 weeks of fish protein supplementation resulted in lower values of fasting glucose (Pfish protein supplementation compared to controls. Glucose-AUC was decreased after 8 weeks with fish protein supplement compared to baseline (Pfish protein may have beneficial effects on blood levels of glucose and LDL-cholesterol as well as glucose tolerance and body composition in overweight adults. The long-term effects of fish protein supplementation is of interest in the context of using more fish as a protein source in the diet, and the effects of inclusion of fish in the diet of individuals with low glucose tolerance should be evaluated.

  3. Fasting plasma glucose in young adults free of diabetes is associated with cognitive function in midlife.

    Science.gov (United States)

    Cohen-Manheim, Irit; Sinnreich, Ronit; Doniger, Glen M; Simon, Ely S; Pinchas-Mizrachi, Ronit; Kark, Jeremy D

    2018-06-01

    Evidence for an association of fasting plasma glucose (FPG) with cognitive function in adults free of diabetes is scarce and based on middle-aged and older adults. We examined the association of FPG, measured at age 30, and of change in FPG from age 30 to 43, with cognitive function at age 50. 505 nondiabetic participants of the population-based Jerusalem Lipid Research Clinic (LRC) cohort study had baseline FPG, 2-h post-oral challenge plasma glucose (OGTT) and insulin determined at ages 28-32, and FPG and OGTT again at ages 41-46. Subsequently at ages 48-52, global cognitive function and its five specific component domains were assessed with a NeuroTrax computerized test battery, using multiple linear regression and multivariable logistic models. Hyperglycemia (FPG ≥ 5.6 mmol/l vs. <5.6 mmol/l) at baseline was associated with poorer global cognitive function in midlife (predominantly in the visual spatial and attention domains), independent of socio-demographic characteristics, life style variables, body mass index (BMI), and inflammatory and biochemical variables (standardized Beta = -0.121, P = 0.002, plinear trend(FPG continuous) =0.016). Similarly, increased odds for low-ranked (lowest fifth) global cognition was evident (ORper mmol/l FPG=2.31, 95% CI = 1.30-4.13, P = 0.005). Baseline OGTT, insulin resistance (HOMA-IR) and change in FPG and OGTT over 13 years were not associated with cognition. A higher FPG in young adults was associated with lower cognitive performance in midlife. Although we cannot dismiss the possibility of reverse causation, hyperglycemia at a young age may be a modifiable risk factor for low-ranked cognitive function in midlife.

  4. Improving Detection of Prediabetes in Children and Adults: Using Combinations of Blood Glucose Tests

    Directory of Open Access Journals (Sweden)

    Ike Solomon Okosun

    2015-11-01

    Full Text Available Aim: To determine combinations of blood glucose tests: oral glucose tolerance (OGT, fasting plasma glucose (FBG and hemoglobin A1C (HbA1C that are associated with highest diagnostic rates of prediabetes in non-diabetic American children and adults.Methods: The 2007-2008 U.S. National Health and Nutrition Examination Surveys data were used for this study. Overall and specific prevalence of prediabetes (defined using OGT+FPG, OGT+HbA1C, HbA1C+FPG and OGT+FPG+HbA1C tests were determined across age, race/ethnicity, sex and BMI categories.Results: FPG+HbA1C test was associated with significantly higher diagnostic rates of prediabetes across age, race/ethnicity and BMI. Estimates of overall prevalence of prediabetes using OGT+FPG, OGT+HbA1C, HbA1C+FPG and OGT+FPG+HbA1C tests were 20.3%, 24.2%, 33% and 34.3%, respectively. Compared to OGT+FPG, the use of HbA1C+FPG test in screening was associated with 44.8%, 135%, 38.6% and 35.9% increased prevalence of prediabetes in non-Hispanic White, non-Hispanic Black, Mexican-American and other racial/ethnic men, respectively. The corresponding values in women were 67.8%, 140%, 37.2% and 42.6%, respectively. Combined use of all blood glucose tests did not improve the overall and gender-specific prediabetes prevalence beyond what was observed using HbA1C+FPG test.Conclusions: HbA1C criteria were associated with higher diagnosis rates of prediabetes than FPG and OGT tests in non-diabetic American children and adults. Using a combination of HbA1C and FPG test in screening for prediabetes reduces intrinsic systematic bias in using just HbA1C testing and offers the benefits of each test. A well-defined HbA1C that takes into consideration race/ethnicity, gender, age and body mass index may improve detection of prediabetes in population and clinical settings.

  5. Effects of Low-Molecular-Weight Fucoidan and High Stability Fucoxanthin on Glucose Homeostasis, Lipid Metabolism, and Liver Function in a Mouse Model of Type II Diabetes

    Directory of Open Access Journals (Sweden)

    Hong-Ting Victor Lin

    2017-04-01

    Full Text Available The combined effects of low-molecular-weight fucoidan (LMF and fucoxanthin (Fx in terms of antihyperglycemic, antihyperlipidemic, and hepatoprotective activities were investigated in a mouse model of type II diabetes. The intake of LMF, Fx, and LMF + Fx lowered the blood sugar and fasting blood sugar levels, and increased serum adiponectin levels. The significant decrease in urinary sugar was only observed in LMF + Fx supplementation. LMF and Fx had ameliorating effects on the hepatic tissue of db/db mice by increasing hepatic glycogen and antioxidative enzymes, and LMF was more effective than Fx at improving hepatic glucose metabolism. As for glucose and lipid metabolism in the adipose tissue, the expression of insulin receptor substrate (IRS-1, glucose transporter (GLUT, peroxisome proliferator-activated receptor gamma (PPARγ, and uncoupling protein (UCP-1 mRNAs in the adipose tissue of diabetic mice was significantly upregulated by Fx and LMF + Fx, and levels of inflammatory adipocytokines, such as adiponectin, tumor necrosis factor-α (TNF-α, and interleukin-6 (IL-6, were significantly modulated only by LMF + Fx supplementation. The efficacy of LMF + Fx supplementation on the decrease in urinary sugar and on glucose and lipid metabolism in the white adipose tissue of db/db mice was better than that of Fx or LMF alone, indicating the occurrence of a synergistic effect of LMF and Fx.

  6. Glucose allostasis

    DEFF Research Database (Denmark)

    Stumvoll, Michael; Tataranni, P Antonio; Stefan, Norbert

    2003-01-01

    individuals with normal glucose tolerance, normoglycemia can always be maintained by compensatorily increasing AIR in response to decreasing M (and vice versa). This has been mathematically described by the hyperbolic relationship between AIR and M and referred to as glucose homeostasis, with glucose......In many organisms, normoglycemia is achieved by a tight coupling of nutrient-stimulated insulin secretion in the pancreatic beta-cell (acute insulin response [AIR]) and the metabolic action of insulin to stimulate glucose disposal (insulin action [M]). It is widely accepted that in healthy...... concentration assumed to remain constant along the hyperbola. Conceivably, glucose is one of the signals stimulating AIR in response to decreasing M. Hypothetically, as with any normally functioning feed-forward system, AIR should not fully compensate for worsening M, since this would remove the stimulus...

  7. Effects of ozone on adult and aged lung oxygen consumption, glucose metabolism and G6PDH activity

    International Nuclear Information System (INIS)

    Raska-Emery, P.; Balis, J.U.; Montgomery, M.R.

    1991-01-01

    Fischer-344 male adult (4-6 mo) and aged (24-26 mo) rats were exposed to 0-3.0 ppm O 3 for 8h, sacrificed immediately, and O 2 consumption, 1 C 14 -glucose metabolism and G6PDH activity were determined. For O 2 consumption, the exp to 0.5 ppm O 3 produced a stimulation in both age groups. Decrements in O 2 consumption were only evident in aged rats after 1.5 and 3.0 ppm. Glucose metabolism showed a marked difference rats were 40% adult rats. Control values in aged rats were 40% of adults. Exp to 0.5 ppm was stimulatory in adults and aged, while 1.5 and 3.0 pp, decreased glucose metabolism in both groups. No age-related difference in G6PDH activity between control and exposed was seen. However, in both age groups, 0.5 ppm O 3 resulted in a significant increase in activity (33-41%)l 1.5 and 3.0 ppm were without effect. The combined results show a biphasic response of adult and aged lung to severe, acute O 3 exp. One-half ppm O 3 for 8h is stimulatory for all three parameters examined in both age groups. Three ppm O 3 inhibits O 2 consumption and glucose metabolism in both age groups but is ineffective on G6PDH activity

  8. Diet enriched with fresh coconut decreases blood glucose levels and body weight in normal adults.

    Science.gov (United States)

    Vijayakumar, Venugopal; Shankar, Nagashree R; Mavathur, Ramesh; Mooventhan, A; Anju, Sood; Manjunath, N K

    2018-02-20

    Background There exist controversies about the health effects of coconut. Fresh coconut consumption on human health has not been studied substantially. Fresh coconut consumption is a regular part of the diet for many people in tropical countries like India, and thus there is an increasing need to understand the effects of fresh coconut on various aspects of health. Aim To compare the effects of increased saturated fatty acid (SFA) and fiber intake, provided by fresh coconut, versus monounsaturated fatty acid (MUFA) and fiber intake, provided by a combination of groundnut oil and groundnuts, on anthropometry, serum insulin, glucose levels and blood pressure in healthy adults. Materials Eighty healthy volunteers, randomized into two groups, were provided with a standardized diet along with either 100 g fresh coconut or an equivalent amount of groundnuts and groundnut oil for a period of 90 days. Assessments such as anthropometric measurements, blood pressure, blood sugar and insulin levels were performed before and after the supplementation period. Results Results of this study showed a significant reduction in fasting blood sugar (FBS) in both the groups. However, a significant reduction in body weight was observed in the coconut group, while a significant increase in diastolic pressure was observed in the groundnut group. Conclusions Results of this study suggest that fresh coconut-added diet helps reduce blood glucose levels and body weight in normal healthy individuals.

  9. Regional cerebral glucose metabolism is normal in young adults with Down syndrome

    International Nuclear Information System (INIS)

    Schapiro, M.B.; Grady, C.L.; Kumar, A.; Herscovitch, P.; Haxby, J.V.; Moore, A.M.; White, B.; Friedland, R.P.; Rapoport, S.I.

    1990-01-01

    Regional CMRglc (rCMRglc) values were measured with [ 18 F]2-fluoro-2-deoxy-D-glucose ( 18 FDG) and positron emission tomography (PET), using a Scanditronix PC-1024-7B scanner, in 14 healthy, noninstitutionalized subjects with trisomy 21 (Down syndrome; DS) (mean age 30.0 years, range 25-38 years) and in 13 sex-matched, healthy volunteers (mean age 29.5 years, range 22-38 years). In the DS group, mean mental age on the Peabody Picture Vocabulary Test was 7.8 years and dementia was not present. Resting rCMRglc was determined with eyes covered and ears occluded in a quiet, darkened room. Global gray CMRglc equaled 8.76 +/- 0.76 mg/100 g/min (mean +/- SD) in the DS group as compared with 8.74 +/- 1.19 mg/100 g/min in the control group (p greater than 0.05). Gray matter regional measurements also did not differ between groups. The ratio of rCMRglc to global CMRglc, calculated to reduce the variance associated with absolute rCMRglc, and right/left ratios did not show any consistent differences. These results show that healthy young DS adults do not have alterations in regional or global brain glucose metabolism, as measured with 18FDG and PET, prior to an age at which the neuropathological changes in Alzheimer disease are reported to occur

  10. Metabolomics reveals that vine tea (Ampelopsis grossedentata prevents high-fat-diet-induced metabolism disorder by improving glucose homeostasis in rats.

    Directory of Open Access Journals (Sweden)

    Wenting Wan

    Full Text Available Vine tea (VT, derived from Ampelopsis grossedentata (Hand.-Mazz. W.T. Wang, is an alternative tea that has been consumed widely in south China for hundreds of years. It has been shown that drinking VT on a daily basis improves hyperlipidemia and hyperglycemia. However, little is known about the preventive functions of VT for metabolic dysregulation and the potential pathological mechanisms involved. This paper elucidates the preventive effects of VT on the dysregulation of lipid and glucose metabolism using rats maintained on a high-fat-diet (HFD in an attempt to explain the potential mechanisms involved.Sprague Dawley (SD rats were divided into five groups: a group given normal rat chow and water (control group; a group given an HFD and water (HFD group; a group given an HFD and Pioglitazone (PIO group, 5 mg /kg; and groups given an HFD and one of two doses of VT: 500 mg/L or 2000 mg/L. After 8 weeks, changes in food intake, tea consumption, body weight, serum and hepatic biochemical parameters were determined. Moreover, liver samples were isolated for pathology histology and liquid chromatography-mass spectrometry (LC-MS-based metabolomic research.VT reduced the serum levels of glucose and total cholesterol, decreased glucose area under the curve in the insulin tolerance test and visibly impaired hepatic lipid accumulation. Metabolomics showed that VT treatment modulated the contents of metabolic intermediates linked to glucose metabolism (including gluconeogenesis and glycolysis, the TCA cycle, purine metabolism and amino acid metabolism.The current results demonstrate that VT may prevent metabolic impairments induced by the consumption of an HFD. These effects may be caused by improved energy-related metabolism (including gluconeogenesis, glycolysis and TCA cycle, purine metabolism and amino acid metabolism, and reduced lipid levels in the HFD-fed rats.

  11. Green tea and vitamin E enhance exercise-induced benefits in body composition, glucose homeostasis, and antioxidant status in elderly men and women.

    Science.gov (United States)

    Narotzki, Baruch; Reznick, Abraham Z; Navot-Mintzer, Dalya; Dagan, Bracha; Levy, Yishai

    2013-01-01

    To investigate the effects of green tea plus vitamin E in addition to exercise on body composition and metabolic and antioxidant parameters in healthy elderly individuals. Interventional randomized controlled prospective trial. For 12 weeks, 22 elderly men and women (age: 71.1 ± 1.2 years; body mass index: 28.3 ± 0.5 kg/m(2) [mean ± SE]) undertook 30 minutes of moderately intense walking 6 d/wk. They were randomly assigned to ingest either green tea plus vitamin E (GTVE; 3 cups and 400 IU, respectively; n = 11) or placebo (n = 11). Data on anthropometrics, fasting insulin and glucose levels, physical fitness, dietary intake, safety parameters, and biomarkers of oxidation status were recorded and analyzed at the start and end of the study. Though dietary intake was unchanged, improved exercise capacity was followed by a significant reduction in body weight and fasting insulin levels in all participants. Additional consumption of GTVE resulted in a twofold increase in serum vitamin E (from 20.4 to 40.6 μmol/L, p fasting glucose levels (from 5.30 to 4.98 mmol/L, p benefits in body composition and glucose tolerance and may also lower oxidative burden.

  12. Fasting Triglycerides and Glucose Index as a Diagnostic Test for Insulin Resistance in Young Adults.

    Science.gov (United States)

    Guerrero-Romero, Fernando; Villalobos-Molina, Rafael; Jiménez-Flores, J Rafael; Simental-Mendia, Luis E; Méndez-Cruz, René; Murguía-Romero, Miguel; Rodríguez-Morán, Martha

    2016-07-01

    Although the Glucose and Triglyceride levels (TyG) index is useful for identification of insulin resistance (IR) in different ethnic groups, it has not been evaluated in young adults. We undertook this study to evaluate the TyG index as a diagnostic test for IR in young adults. A total of 5,538 healthy young adults, 3,795 (68.5%) non-pregnant women and 1,743 (31.5%) men, with an average age of 19.2 ± 1.4 years, were enrolled in a population-based cross-sectional study. To estimate diagnostic characteristics of the TyG index, a randomized subsample of the target population (n = 75) was under euglycemic-hyperinsulinemic clamp test. Using the cutoff values obtained in the clamp study, the diagnostic concordance between TyG index and HOMA-IR was evaluated in the overall population. The TyG index was calculated as the Ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)]/2. Normal weight, overweight, and obesity were identified in 3,632 (65.6%), 1,355 (24.5%), and 551 (9.9%) participants. A total of 346 (9.1%) men and 278 (15.9%) women exhibited IR. The best cutoff value of TyG index for diagnosis of IR was 4.55 (sensitivity 0.687, negative predictive value (NPV) 0.844, and negative likelihood ratio (NLR) 0.47) for women and 4.68 (sensitivity 0.673, NPV 0.900, and NLR 0.45) for men. In normal-weight individuals the diagnostic concordance between TyG index and HOMA-IR was 0.934 and 0.915, in the overweight subjects was 0.908 and 0.895 and, in the obese participants 0.916 and 0.950, for men and women, respectively. TyG index may be useful for screening IR in young adults. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

  13. Clinical use of continuous glucose monitoring in adults with type 1 diabetes

    OpenAIRE

    Slattery, David; Choudhary, Pratik

    2017-01-01

    With the emphasis on intensive management of type 1 diabetes, data from studies support frequent monitoring of glucose levels to improve glycemic control and reduce glucose variability, which can be related to an increase in macro and microvascular complications. However, few perform capillary blood glucose that frequently. There are currently two available alternatives that this review will discuss, continuous glucose monitoring (CGM) and flash glucose monitoring. CGM has become an important...

  14. Diurnal Variations in Serum Glucose, Insulin and C-Peptide of Normal Korean Adults

    International Nuclear Information System (INIS)

    Choi, Du Hyok; Chung, June Key; Lee, Hong Kyu; Koh, Chang Soon; Hong, Kee Suk

    1983-01-01

    It is already well known that many factors are involved in maintaining normal blood glucose level. The amount and components of meal are also thought to be some of the factors which affect the blood glucose and insulin levels. It is reported that as for Koreans sugar takes up over 75% out of 2,098 kcal, the average daily calorie intake per adult. It implies that Koreans take a high-sugar diet compared with Westerners who take 40-50% of sugar out of their total average daily calorie. For the purpose of studying diurnal variations in serum glucose, insulin and C-peptide of normal Koreans adults based on ordinary Korean diet, we selected 13 normal Korean male adults and divided them into two groups, Group I (7 persons) and Group II (6 persons). We put Group I on 3,100 kcal and 75% sugar diet, and Group II on 2,100 kcal and 69% sugar diet per day for over 4 days. Serum glucose, insulin and C-peptide were checked every 30 minutes or every hour throughout 2 hour. Results are as follows: 1. As for serum glucose level, in the preprandial fasting state in the morning, mean±S.D. of Group I was 91.1±3.2 mg%, while that of Group II is 82.5±4.4 mg%. Both groups showed peaks of increased glucose level t postprandial 1 hour after each meal. The peak returned to the level shown during the fasting state at postprandial 1 hour after breakfast while the relatively high glucose levels were maintained respectively even for 2 or 3 hours after lunch and dinner. 2. As for serum insults level, Group I showed mean±S.D. of 14.7±3.0 μU/ml while Group II shows that of 7.0±2.6 μU/ml in the fasting state. Group I particularly showed the largest peak from preprandial a half or one and half an hour to postprandial one hour of lunch, and made relatively small peaks (47.7±10.8 μU/ml) at postprandial 1 hour after breakfast and dinner. No such large peak was marked in Group II, though it showed relatively similar patterns of peak after each meal. 3. As for C-peptide, in the fasting state

  15. Diurnal Variations in Serum Glucose, Insulin and C-Peptide of Normal Korean Adults

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Du Hyok; Chung, June Key; Lee, Hong Kyu; Koh, Chang Soon [Seoul National University College of Medicine, Seoul (Korea, Republic of); Hong, Kee Suk [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1983-03-15

    It is already well known that many factors are involved in maintaining normal blood glucose level. The amount and components of meal are also thought to be some of the factors which affect the blood glucose and insulin levels. It is reported that as for Koreans sugar takes up over 75% out of 2,098 kcal, the average daily calorie intake per adult. It implies that Koreans take a high-sugar diet compared with Westerners who take 40-50% of sugar out of their total average daily calorie. For the purpose of studying diurnal variations in serum glucose, insulin and C-peptide of normal Koreans adults based on ordinary Korean diet, we selected 13 normal Korean male adults and divided them into two groups, Group I (7 persons) and Group II (6 persons). We put Group I on 3,100 kcal and 75% sugar diet, and Group II on 2,100 kcal and 69% sugar diet per day for over 4 days. Serum glucose, insulin and C-peptide were checked every 30 minutes or every hour throughout 2 hour. Results are as follows: 1. As for serum glucose level, in the preprandial fasting state in the morning, mean+-S.D. of Group I was 91.1+-3.2 mg%, while that of Group II is 82.5+-4.4 mg%. Both groups showed peaks of increased glucose level t postprandial 1 hour after each meal. The peak returned to the level shown during the fasting state at postprandial 1 hour after breakfast while the relatively high glucose levels were maintained respectively even for 2 or 3 hours after lunch and dinner. 2. As for serum insults level, Group I showed mean+-S.D. of 14.7+-3.0 muU/ml while Group II shows that of 7.0+-2.6 muU/ml in the fasting state. Group I particularly showed the largest peak from preprandial a half or one and half an hour to postprandial one hour of lunch, and made relatively small peaks (47.7+-10.8 muU/ml) at postprandial 1 hour after breakfast and dinner. No such large peak was marked in Group II, though it showed relatively similar patterns of peak after each meal. 3. As for C-peptide, in the fasting state

  16. Examination of the effects of arsenic on glucose homeostasis in cell culture and animal studies: Development of a mouse model for arsenic-induced diabetes

    International Nuclear Information System (INIS)

    Paul, David S.; Hernandez-Zavala, Araceli; Walton, Felecia S.; Adair, Blakely M.; Dedina, Jiri; Matousek, Tomas; Styblo, Miroslav

    2007-01-01

    Previous epidemiologic studies found increased prevalences of type 2 diabetes mellitus in populations exposed to high levels of inorganic arsenic (iAs) in drinking water. Although results of epidemiologic studies in low-exposure areas or occupational settings have been inconclusive, laboratory research has shown that exposures to iAs can produce effects that are consistent with type 2 diabetes. The current paper reviews the results of laboratory studies that examined the effects of iAs on glucose metabolism and describes new experiments in which the diabetogenic effects of iAs exposure were reproduced in a mouse model. Here, weanling male C57BL/6 mice drank deionized water with or without the addition of arsenite (25 or 50 ppm As) for 8 weeks. Intraperitoneal glucose tolerance tests revealed impaired glucose tolerance in mice exposed to 50 ppm As, but not to 25 ppm As. Exposure to 25 and 50 ppm As in drinking-water resulted in proportional increases in the concentration of iAs and its metabolites in the liver and in organs targeted by type 2 diabetes, including pancreas, skeletal muscle and adipose tissue. Dimethylarsenic was the predominant form of As in the tissues of mice in both 25 and 50 ppm groups. Notably, the average concentration of total speciated arsenic in livers from mice in the 50 ppm group was comparable to the highest concentration of total arsenic reported in the livers of Bangladeshi residents who had consumed water with an order of magnitude lower level of iAs. These data suggest that mice are less susceptible than humans to the diabetogenic effects of chronic exposure to iAs due to a more efficient clearance of iAs or its metabolites from target tissues

  17. Critical Role of the Src Homology 2 (SH2) Domain of Neuronal SH2B1 in the Regulation of Body Weight and Glucose Homeostasis in Mice

    OpenAIRE

    Morris, David L.; Cho, Kae Won; Rui, Liangyou

    2010-01-01

    SH2B1 is an SH2 domain-containing adaptor protein that plays a key role in the regulation of energy and glucose metabolism in both rodents and humans. Genetic deletion of SH2B1 in mice results in obesity and type 2 diabetes. Single-nucleotide polymorphisms in the SH2B1 loci and chromosomal deletions of the SH2B1 loci associate with obesity and insulin resistance in humans. In cultured cells, SH2B1 promotes leptin and insulin signaling by binding via its SH2 domain to phosphorylated tyrosines ...

  18. Brain glucose metabolism in adults with ataxia-telangiectasia and their asymptomatic relatives.

    Science.gov (United States)

    Volkow, Nora D; Tomasi, Dardo; Wang, Gene-Jack; Studentsova, Yana; Margus, Brad; Crawford, Thomas O

    2014-06-01

    Ataxia-telangiectasia is a recessive genetic disorder (ATM is the mutated gene) of childhood with severe motor impairments and whereas homozygotes manifest the disorder, heterozygotes are asymptomatic. Structural brain imaging and post-mortem studies in individuals with ataxia-telangiectasia have reported cerebellar atrophy; but abnormalities of motor control characteristic of extrapyramidal dysfunction suggest impairment of broader motor networks. Here, we investigated possible dysfunction in other brain areas in individuals with ataxia-telangiectasia and tested for brain changes in asymptomatic relatives to assess if heterozygocity affects brain function. We used positron emission tomography and (18)F-fluorodeoxyglucose to measure brain glucose metabolism (quantified as µmol/100 g/min), which serves as a marker of brain function, in 10 adults with ataxia-telangiectasia, 19 non-affected adult relatives (12 siblings, seven parents) and 29 age-matched healthy controls. Statistical parametric mapping and region of interest analyses were used to compare individuals with ataxia-telangiectasia, asymptomatic relatives, and unrelated controls. We found that participants with ataxia-telangiectasia had lower metabolism in cerebellar hemispheres (14%, P brain stimulation. Our finding of decreased metabolism in vermis and hippocampus of asymptomatic relatives suggests that heterozygocity influences the function of these brain regions. Published by Oxford University Press on behalf of the Guarantors of Brain 2014. This work is written by US Government employees and is in the public domain in the US.

  19. The Prevalence and Associated Factors of Periodontitis According to Fasting Plasma Glucose in the Korean Adults

    Science.gov (United States)

    Hong, Jae Won; Noh, Jung Hyun; Kim, Dong-Jun

    2016-01-01

    Abstract Although the relationship between diabetes and periodontitis is well established, the association between periodontitis and prediabetes has been investigated less extensively. Furthermore, there has been little research on the prevalence of periodontitis among individuals with prediabetes and diabetes as well as in the overall population using nationally representative data. Among 12,406 adults (≥19 years’ old) who participated in the 2012–2013 Korea National Health and Nutrition Examination Survey, a total of 9977 subjects completed oral and laboratory examinations and were included in this analysis. Periodontitis was defined as a community periodontal index score of ≥3 according to the World Health Organization criteria. The fasting plasma glucose level was categorized into the following 5 groups: normal fasting glucose (NFG) 1 (periodontitis among the Korean adult population was 24.8% (23.3–26.4%) (weight n = 8,455,952/34,086,014). The unadjusted weighted prevalences of periodontitis were 16.7%, 22.8%, 29.6%, 40.7%, and 46.7% in the NFG 1, NFG 2, IFG 1, IFG 2, and diabetes groups, respectively (P periodontitis increased to 29.7% in the IFG 2 group (P = 0.045) and 32.5% in the diabetes group (P periodontitis with the above-mentioned variables as covariates were 1.42 (95% confidence interval [CI] 1.14–1.77, P = 0.002) in the diabetes group and 1.33 (95% CI 1.01–1.75, P = 0.044) in the IFG 2 group, respectively, compared with the NFG1 group. In conclusion, a higher range of IFG levels as well as diabetes, were positively associated with chronic periodontitis in a representative sample of Korean adults. This study suggests that individuals with a higher range of IFG levels before diabetes are at risk of periodontitis, and may benefit from dental screening. PMID:27057854

  20. Association of Insulin Resistance With Cerebral Glucose Uptake in Late Middle-Aged Adults at Risk for Alzheimer Disease.

    Science.gov (United States)

    Willette, Auriel A; Bendlin, Barbara B; Starks, Erika J; Birdsill, Alex C; Johnson, Sterling C; Christian, Bradley T; Okonkwo, Ozioma C; La Rue, Asenath; Hermann, Bruce P; Koscik, Rebecca L; Jonaitis, Erin M; Sager, Mark A; Asthana, Sanjay

    2015-09-01

    Converging evidence suggests that Alzheimer disease (AD) involves insulin signaling impairment. Patients with AD and individuals at risk for AD show reduced glucose metabolism, as indexed by fludeoxyglucose F 18-labeled positron emission tomography (FDG-PET). To determine whether insulin resistance predicts AD-like global and regional glucose metabolism deficits in late middle-aged participants at risk for AD and to examine whether insulin resistance-predicted variation in regional glucose metabolism is associated with worse cognitive performance. This population-based, cross-sectional study included 150 cognitively normal, late middle-aged (mean [SD] age, 60.7 [5.8] years) adults from the Wisconsin Registry for Alzheimer's Prevention (WRAP) study, a general community sample enriched for AD parental history. Participants underwent cognitive testing, fasting blood draw, and FDG-PET at baseline. We used the homeostatic model assessment of peripheral insulin resistance (HOMA-IR). Regression analysis tested the statistical effect of HOMA-IR on global glucose metabolism. We used a voxelwise analysis to determine whether HOMA-IR predicted regional glucose metabolism. Finally, predicted variation in regional glucose metabolism was regressed against cognitive factors. Covariates included age, sex, body mass index, apolipoprotein E ε4 genotype, AD parental history status, and a reference region used to normalize regional uptake. Regional glucose uptake determined using FDG-PET and neuropsychological factors. Higher HOMA-IR was associated with lower global glucose metabolism (β = -0.29; P factor scores. Our results show that insulin resistance, a prevalent and increasingly common condition in developed countries, is associated with significantly lower regional cerebral glucose metabolism, which in turn may predict worse memory performance. Midlife may be a critical period for initiating treatments to lower peripheral insulin resistance to maintain neural metabolism

  1. Combination of the sodium-glucose cotransporter-2 inhibitor empagliflozin with orlistat or sibutramine further improves the body-weight reduction and glucose homeostasis of obese rats fed a cafeteria diet

    Directory of Open Access Journals (Sweden)

    Vickers SP

    2014-07-01

    Full Text Available Steven P Vickers,1 Sharon C Cheetham,1 Katie R Headland,1 Keith Dickinson,1 Rolf Grempler,2 Eric Mayoux,2 Michael Mark,2 Thomas Klein2 1RenaSci, BioCity Nottingham, Nottingham, UK; 2Boehringer Ingelheim Pharma, Biberach an der Riss, Germany Abstract: The present study assessed the potential of the sodium glucose-linked transporter (SGLT-2 inhibitor empagliflozin to decrease body weight when administered alone or in combination with the clinically effective weight-loss agents orlistat and sibutramine in obese rats fed a cafeteria diet. Female Wistar rats were exposed to a cafeteria diet to induce obesity. Empagliflozin was dosed once daily (10, 30, and 60 mg/kg for 28 days. Combination studies were subsequently performed using a submaximal empagliflozin dose (10 mg/kg with either sibutramine or orlistat. Body weight, food, and water intake were recorded daily. The effect of drug treatment on glucose tolerance, relevant plasma parameters, and carcass composition was determined. Empagliflozin dose-dependently reduced body weight, plasma leptin, and body fat though increased urinary glucose excretion. The combination of empagliflozin and orlistat significantly reduced body weight compared to animals treated with either drug alone, and significantly improved glucose tolerance, plasma insulin, and leptin compared to vehicle-treated controls. The effect of sibutramine to improve glycemic control in an oral glucose-tolerance test was also significantly increased, with empagliflozin and combination treatment leading to a reduction in carcass fat greater than that observed with either drug alone. These data demonstrate that empagliflozin reduces body weight in cafeteria-fed obese rats. In combination studies, empagliflozin further improved the body-weight or body-fat loss of animals in comparison to orlistat or sibutramine alone. Such studies may indicate improved strategies for the treatment of obese patients with prediabetes or type 2 diabetes. Keywords

  2. Combination of the sodium-glucose cotransporter-2 inhibitor empagliflozin with orlistat or sibutramine further improves the body-weight reduction and glucose homeostasis of obese rats fed a cafeteria diet.

    Science.gov (United States)

    Vickers, Steven P; Cheetham, Sharon C; Headland, Katie R; Dickinson, Keith; Grempler, Rolf; Mayoux, Eric; Mark, Michael; Klein, Thomas

    2014-01-01

    The present study assessed the potential of the sodium glucose-linked transporter (SGLT)-2 inhibitor empagliflozin to decrease body weight when administered alone or in combination with the clinically effective weight-loss agents orlistat and sibutramine in obese rats fed a cafeteria diet. Female Wistar rats were exposed to a cafeteria diet to induce obesity. Empagliflozin was dosed once daily (10, 30, and 60 mg/kg) for 28 days. Combination studies were subsequently performed using a submaximal empagliflozin dose (10 mg/kg) with either sibutramine or orlistat. Body weight, food, and water intake were recorded daily. The effect of drug treatment on glucose tolerance, relevant plasma parameters, and carcass composition was determined. Empagliflozin dose-dependently reduced body weight, plasma leptin, and body fat though increased urinary glucose excretion. The combination of empagliflozin and orlistat significantly reduced body weight compared to animals treated with either drug alone, and significantly improved glucose tolerance, plasma insulin, and leptin compared to vehicle-treated controls. The effect of sibutramine to improve glycemic control in an oral glucose-tolerance test was also significantly increased, with empagliflozin and combination treatment leading to a reduction in carcass fat greater than that observed with either drug alone. These data demonstrate that empagliflozin reduces body weight in cafeteria-fed obese rats. In combination studies, empagliflozin further improved the body-weight or body-fat loss of animals in comparison to orlistat or sibutramine alone. Such studies may indicate improved strategies for the treatment of obese patients with prediabetes or type 2 diabetes.

  3. The Great Recession worsened blood pressure and blood glucose levels in American adults.

    Science.gov (United States)

    Seeman, Teresa; Thomas, Duncan; Merkin, Sharon Stein; Moore, Kari; Watson, Karol; Karlamangla, Arun

    2018-03-27

    Longitudinal, individual-specific data from the Multi-Ethnic Study of Atherosclerosis (MESA) provide support for the hypothesis that the 2008 to 2010 Great Recession (GR) negatively impacted the health of US adults. Results further advance understanding of the relationship by ( i ) illuminating hypothesized greater negative impacts in population subgroups exposed to more severe impacts of the GR and ( ii ) explicitly controlling for confounding by individual differences in age-related changes in health over time. Analyses overcome limitations of prior work by ( i ) employing individual-level data that avoid concerns about ecological fallacy associated with prior reliance on group-level data, ( ii ) using four waves of data before the GR to estimate and control for underlying individual-level age-related trends, ( iii ) focusing on objective, temporally appropriate health outcomes rather than mortality, and ( iv ) leveraging a diverse cohort to investigate subgroup differences in the GR's impact. Innovative individual fixed-effects modeling controlling for individual-level age-related trajectories yielded substantively important insights: ( i ) significant elevations post-GR for blood pressure and fasting glucose, especially among those on medication pre-GR, and ( ii ) reductions in prevalence and intensity of medication use post-GR. Important differences in the effects of the GR are seen across subgroups, with larger effects among younger adults (who are likely still in the labor force) and older homeowners (whose declining home wealth likely reduced financial security, with less scope for recouping losses during their lifetime); least affected were older adults without a college degree (whose greater reliance on Medicare and Social Security likely provided more protection from the recession).

  4. Leisure Time Physical Activity and Its Determinants among Adults in Tehran: Tehran Lipid and Glucose Study.

    Science.gov (United States)

    Momenan, Amir Abbas; Delshad, Maryam; Mirmiran, Parvin; Ghanbarian, Arash; Azizi, Fereidoun

    2011-10-01

    The aim of this study was to assess leisure time physical activity and its determinants among adults in Tehran. This cross-sectional study comprised adults (n = 7285), aged 20 years and older. The subjects were participants of the Tehran Lipid and Glucose Study between 2002 and 2004. Information on the number of days spent on different activities during a week and the time devoted to each activity on a typical day was recorded. In addition, each activity, weighted by its relative intensity, was referred to as a metabolic equivalent. The prevalence of inactivity was 69.8% (95% CI: 68.7-70.8) in the whole population and 30.2% (95% CI: 27.2-33.1%) of men and 30.3% (95% CI: 27.7-32.8%) of women were considered as active. Leisure time physical activity less than 30 min/week was scored in 1590 (50.6%) men and 1803 (43.5%) women. The most frequent leisure time physical activity performed by men (96.1%) and women (95.2%) was walking. A negative association was observed in men between leisure time physical activity and increased work hours, older age, more cigarette smoking and higher body mass index (69.8% were overweight and 75.3% were obese; P women. The prevalence of physical inactivity among adults in Tehran was high. Leisure time physical inactivity was more likely to be associated with older age, more cigarette smoking, more working hours, and higher body mass index. Public health efforts are needed to improve people's participation in physical activities in Iran.

  5. Impaired Fasting Glucose in Omani Adults with no Family History of Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Sawsan Al-Sinani

    2014-05-01

    Full Text Available Objectives: The aim of this study was to estimate the prevalence of impaired fasting glucose (IFG among Omani adults with no family history (FH of diabetes and to investigate the factors behind the risk of developing type 2 diabetes (T2D, while excluding a FH of diabetes. Methods: A total of 1,182 Omani adults, aged ≥40 years, visited the Family Medicine & Community Health Clinic at Sultan Qaboos University Hospital, Oman, on days other than the Diabetes Clinic days, from July 2010 to July 2011. The subjects were interviewed and asked if they had T2D or a FH of T2D. Results: Only 191 (16% reported no personal history of T2D or FH of the disease. Of these, anthropometric and biochemical data was complete in 159 subjects. Of these a total of 42 (26% had IFG according to the American Diabetes Association criteria. Body mass index, fasting insulin, haemoglobin A1C and blood pressure (BP, were significantly higher among individuals with IFG (P <0.01, P <0.05, P <0.01 and P <0.01, respectively. In addition, fasting insulin, BP and serum lipid profile were correlated with obesity indices (P <0.05. Obesity indices were strongly associated with the risk of IFG among Omanis, with waist circumference being the strongest predictor. Conclusion: Despite claiming no FH of diabetes, a large number of Omani adults in this study had a high risk of developing diabetes. This is possibly due to environmental factors and endogamy. The high prevalence of obesity combined with genetically susceptible individuals is a warning that diabetes could be a future epidemic in Oman.

  6. The Relationship between Physical Activity and Plasma Glucose Level amongst Ellisras Rural Young Adult Males and Females: Ellisras Longitudinal Study

    Directory of Open Access Journals (Sweden)

    Moloko Matshipi

    2017-02-01

    Full Text Available Unhealthy lifestyle characteristics such as low physical activity (PA and high plasma glucose levels (PGLs may lead to the development of type 2 diabetes mellitus in adulthood. The aim of this study was to investigate (i the level of physical activity; (ii the prevalence of pre-diabetes and (iii the relationship between PA and plasma glucose level in a rural Ellisras adult population aged 18 to 28 years. A total of 713 young adults (349 males and 364 females who took part in the Ellisras Longitudinal Study participated in the study. Fasting plasma glucose levels were analysed using Accutrend glucose meters. Physical activity data was collected using a validated questionnaire. Linear regression was used to assess the relationship between PA and pre-diabetes. The prevalence of pre-diabetes was between 45.7% and 50.2% and that of physical inactivity was 67.3% and 71.0% for males and females, respectively. There was no significant (p > 0.05 relationship between PA and pre-diabetes (beta = 1.016; 95% Confidence Interval from 0.352 to 2.777. The health benefits of PA increased with the increasing frequency, duration and intensity of exercise. The prevalence of pre-diabetes was found to be very high in this population. Our results suggest that greater physical activity is associated with low plasma glucose levels.

  7. Critical role of the Src homology 2 (SH2) domain of neuronal SH2B1 in the regulation of body weight and glucose homeostasis in mice.

    Science.gov (United States)

    Morris, David L; Cho, Kae Won; Rui, Liangyou

    2010-08-01

    SH2B1 is an SH2 domain-containing adaptor protein that plays a key role in the regulation of energy and glucose metabolism in both rodents and humans. Genetic deletion of SH2B1 in mice results in obesity and type 2 diabetes. Single-nucleotide polymorphisms in the SH2B1 loci and chromosomal deletions of the SH2B1 loci associate with obesity and insulin resistance in humans. In cultured cells, SH2B1 promotes leptin and insulin signaling by binding via its SH2 domain to phosphorylated tyrosines in Janus kinase 2 and the insulin receptor, respectively. Here we generated three lines of mice to analyze the role of the SH2 domain of SH2B1 in the central nervous system. Transgenic mice expressing wild-type, SH2 domain-defective (R555E), or SH2 domain-alone (DeltaN503) forms of SH2B1 specifically in neurons were crossed with SH2B1 knockout mice to generate KO/SH2B1, KO/R555E, or KO/DeltaN503 compound mutant mice. R555E had a replacement of Arg(555) with Glu within the SH2 domain. DeltaN503 contained an intact SH2 domain but lacked amino acids 1-503. Neuron-specific expression of recombinant SH2B1, but not R555E or DeltaN503, corrected hyperphagia, obesity, glucose intolerance, and insulin resistance in SH2B1 null mice. Neuron-specific expression of R555E in wild-type mice promoted obesity and insulin resistance. These results indicate that in addition to the SH2 domain, N-terminal regions of neuronal SH2B1 are also required for the maintenance of normal body weight and glucose metabolism. Additionally, mutations in the SH2 domain of SH2B1 may increase the susceptibility to obesity and type 2 diabetes in a dominant-negative manner.

  8. Effect of Fasting Blood Glucose Level on Heart Rate Variability of Healthy Young Adults.

    Directory of Open Access Journals (Sweden)

    Mohamed Faisal Lutfi

    Full Text Available Previous studies reported increased risk of cardiac events in subjects with fasting blood glucose (FBG levels lower than the diagnostic threshold of diabetes mellitus. However, whether increased cardiac events in those with upper normal FBG is secondary to the shift of their cardiac sympathovagal balance towards sympathetic predominance is unknown.To assess the association between FBG levels and cardiac autonomic modulation (CAM in euglycaemic healthy subjects based on heart rate variability (HRV derived indices.The study enrolled 42 healthy young adults. Following sociodemographic and clinical assessment, blood samples were collected to measure FBG levels. Five minutes ECG recordings were performed to all participants to obtain frequency domain HRV measurements, namely the natural logarithm (Ln of total power (LnTP, very low frequency (LnVLF, low frequency (LnLF and high frequency (LnHF, low frequency/ high frequency ratio (LnLF/HF, normalized low frequency (LF Norm and high frequency (HF Norm.FBG levels correlated positively with LnHF (r = 0.33, P = 0.031 and HF Norm (r = 0.35, P = 0.025 and negatively with LF Norm (r = -0.35, P = 0.025 and LnLF/HF (r = -0.33, P = 0.035. LnHF and HF Norm were significantly decreased in subjects with the lower (4.00 (1.34 ms2/Hz and 33.12 (11.94 n.u compared to those with the upper FBG quartile (5.64 (1.63 ms2/Hz and 49.43 (17.73 n.u, P = 0.013 and 0.032 respectively. LF Norm and LnLF/HF were significantly increased in subjects with the lower (66.88 (11.94 n.u and 0.73 (0.53 compared to those with the higher FBG quartile (50.58 (17.83 n.u and 0.03 (0.79, P = 0.032 and 0.038 respectively.The present study is the first to demonstrate that rise of blood glucose concentration, within physiological range, is associated with higher parasympathetic, but lower sympathetic CAM. Further researches are needed to set out the glycemic threshold beyond which further increase in glucose level readjusts sympathovagal balance

  9. Effects of adrenergic agents on intracellular ca(2+) homeostasis and metabolism of glucose in astrocytes with an emphasis on pyruvate carboxylation, oxidative decarboxylation and recycling

    DEFF Research Database (Denmark)

    Obel, Linea Lykke Frimodt; Andersen, Karen M H; Bak, Lasse Kristoffer

    2012-01-01

    and oxidative decarboxylation in astrocytic glucose metabolism. Importantly, pyruvate carboxylation was best visualized at 10 min of incubation. The abundance and pattern of labeling in lactate and alanine indicated not only an extensive activity of malic enzyme (initial step for pyruvate recycling) but also...... a high degree of compartmentalization of the pyruvate pool. Stimulating with 1 µM NE had no effect on labeling patterns and glycogen metabolism, whereas 100 µM NE increased glutamate labeling and decreased labeling in alanine, the latter supposedly due to dilution from degradation of non-labeled glycogen....... It is suggested that further experiments uncovering the correlation between adrenergic and glutamatergic pathways should be performed in order to gain further insight into the role of astrocytes in brain function and dysfunction, the latter including excitotoxicity....

  10. Effect of chromium chloride supplementation on glucose tolerance and serum lipids including high-density lipoprotein of adult men.

    Science.gov (United States)

    Riales, R; Albrink, M J

    1981-12-01

    Chromium deficiency may cause insulin resistance, hyperinsulinemia, impaired glucose tolerance, and hyperlipidemia, recovered by chromium supplementation. The effect of chromium supplementation on serum lipids and glucose tolerance was tested in a double-blind 12-wk study of 23 healthy adult men aged 31 to 60 yr. Either 200 micrograms trivalent chromium in 5 ml water (Cr) or 5 ml plain water (W) was ingested daily 5 days each week. Half the subjects volunteered for glucose tolerance tests with insulin levels. At 12 wk high-density lipoprotein cholesterol increased in the Cr group from 35 to 39 mg/dl (p less than 0.05) but did not change in the water group (34 mg/dl). The largest increase in high-density lipoprotein cholesterol and decreases in insulin and glucose were found in those subjects having normal glucose levels together with elevated insulin levels at base-line. The data are thus consistent with the hypothesis that Cr supplementation raises high-density lipoprotein cholesterol and improves insulin sensitivity in those with evidence of insulin resistance but normal glucose tolerance.

  11. Effects of Ramadan Fasting on Glucose Homeostasis, Lipid Profiles, Inflammation and Oxidative Stress in Women with Polycystic Ovary Syndrome in Kashan, Iran.

    Science.gov (United States)

    Asemi, Zatollah; Samimi, Mansooreh; Taghizadeh, Mohsen; Esmaillzadeh, Ahmad

    2015-12-01

    To our knowledge, no reports are available indicating the effects of Ramadan fasting on metabolic parameters, inflammatory factors and oxidative stress in polycystic ovary syndrome (PCOS). The current study was designed to evaluate the effects of Ramadan fasting on metabolic status among women with PCOS. This cross-sectional study was conducted on twenty seven PCOS patients who had fasted for a mean period of 16.5 hours a day during the 29 days of the month of Ramadan in Kashan, Iran. Fasting blood samples were collected at the beginning of the study and after 29 days of the study to quantify related variables. To identify within-group differences (before and after Ramadan), paired-samples t-tests were used. Plasma nitric oxide (NO) levels in PCOS women after Ramadan fasting were significantly higher compared to the baseline values (70.63 ± 15.78 vs. 59.94 ± 13.87 μmol/L, P = 0.003). Post-Ramadan levels of plasma glutathione (GSH) increased significantly in comparison with pre-Ramadan (974.95 ± 414.20 vs. 746.96 ± 205.93 μmol/L, P = 0.011). In addition, a trend toward a significant effect of Ramadan fasting on reducing serum high sensitivity C-reactive protein (hs-CRP) concentrations (2001.07 ± 1686.08 vs. 2962.72 ± 2845.21 ng/mL, P = 0.072) was seen. We did not observe any significant effect of Ramadan fasting on glucose hemostasis parameters, lipid profiles or total antioxidant capacity (TAC). In conclusion, Ramadan fasting in women with PCOS for 4 weeks had beneficial effects on NO and GSH levels, but did not affect glucose hemostasis parameters, lipid profiles or TAC.

  12. Heterozygous Hfe gene deletion leads to impaired glucose homeostasis, but not liver injury in mice fed a high-calorie diet.

    Science.gov (United States)

    Britton, Laurence; Jaskowski, Lesley; Bridle, Kim; Santrampurwala, Nishreen; Reiling, Janske; Musgrave, Nick; Subramaniam, V Nathan; Crawford, Darrell

    2016-06-01

    Heterozygous mutations of the Hfe gene have been proposed as cofactors in the development and progression of nonalcoholic fatty liver disease (NAFLD). Homozygous Hfe deletion previously has been shown to lead to dysregulated hepatic lipid metabolism and accentuated liver injury in a dietary mouse model of NAFLD We sought to establish whether heterozygous deletion of Hfe is sufficient to promote liver injury when mice are exposed to a high-calorie diet (HCD). Eight-week-old wild-type and Hfe(+/-) mice received 8 weeks of a control diet or HCD Liver histology and pathways of lipid and iron metabolism were analyzed. Liver histology demonstrated that mice fed a HCD had increased NAFLD activity score (NAS), steatosis, and hepatocyte ballooning. However, liver injury was unaffected by Hfe genotype. Hepatic iron concentration (HIC) was increased in Hfe(+/-) mice of both dietary groups. HCD resulted in a hepcidin-independent reduction in HIC Hfe(+/-) mice demonstrated raised fasting serum glucose concentrations and HOMA-IR score, despite unaltered serum adiponectin concentrations. Downstream regulators of hepatic de novo lipogenesis (pAKT, SREBP-1, Fas, Scd1) and fatty acid oxidation (AdipoR2, Pparα, Cpt1) were largely unaffected by genotype. In summary, heterozygous Hfe gene deletion is associated with impaired iron and glucose metabolism. However, unlike homozygous Hfe deletion, heterozygous gene deletion did not affect lipid metabolism pathways or liver injury in this model. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  13. Dietary fructose and risk of metabolic syndrome in adults: Tehran Lipid and Glucose study

    Directory of Open Access Journals (Sweden)

    Hosseinpanah Farhad

    2011-07-01

    Full Text Available Abstract Background Studies have shown that the excessive fructose intake may induce adverse metabolic effects. There is no direct evidence from epidemiological studies to clarify the association between usual amounts of fructose intake and the metabolic syndrome. Objective The aim this study was to determine the association of fructose intake and prevalence of metabolic syndrome (MetS and its components in Tehranian adults. Methods This cross-sectional population based study was conducted on 2537 subjects (45% men aged 19-70 y, participants of the Tehran Lipid and Glucose Study (2006-2008. Dietary data were collected using a validated 168 item semi-quantitative food frequency questionnaire. Dietary fructose intake was calculated by sum of natural fructose (NF in fruits and vegetables and added fructose (AF in commercial foods. MetS was defined according to the modified NCEP ATP III for Iranian adults. Results The mean ages of men and women were 40.5 ± 13.6 and 38.6 ± 12.8 years, respectively. Mean total dietary fructose intakes were 46.5 ± 24.5 (NF: 19.6 ± 10.7 and AF: 26.9 ± 13.9 and 37.3 ± 24.2 g/d (NF: 18.6 ± 10.5 and AF: 18.7 ± 13.6 in men and women, respectively. Compared with those in the lowest quartile of fructose intakes, men and women in the highest quartile, respectively, had 33% (95% CI, 1.15-1.47 and 20% (95% CI, 1.09-1.27 higher risk of the metabolic syndrome; 39% (CI, 1.16-1.63 and 20% (CI, 1.07-1.27 higher risk of abdominal obesity; 11% (CI, 1.02-1.17 and 9% (CI, 1.02-1.14 higher risk of hypertension; and 9% (CI, 1-1.15 and 9% (1.04-1.12 higher risk of impaired fasting glucose. Conclusion Higher consumption of dietary fructose may have adverse metabolic effects.

  14. Dietary fructose and risk of metabolic syndrome in adults: Tehran Lipid and Glucose study.

    Science.gov (United States)

    Hosseini-Esfahani, Firoozeh; Bahadoran, Zahra; Mirmiran, Parvin; Hosseinpour-Niazi, Somayeh; Hosseinpanah, Farhad; Azizi, Fereidoun

    2011-07-12

    Studies have shown that the excessive fructose intake may induce adverse metabolic effects. There is no direct evidence from epidemiological studies to clarify the association between usual amounts of fructose intake and the metabolic syndrome. The aim this study was to determine the association of fructose intake and prevalence of metabolic syndrome (MetS) and its components in Tehranian adults. This cross-sectional population based study was conducted on 2537 subjects (45% men) aged 19-70 y, participants of the Tehran Lipid and Glucose Study (2006-2008). Dietary data were collected using a validated 168 item semi-quantitative food frequency questionnaire. Dietary fructose intake was calculated by sum of natural fructose (NF) in fruits and vegetables and added fructose (AF) in commercial foods. MetS was defined according to the modified NCEP ATP III for Iranian adults. The mean ages of men and women were 40.5 ± 13.6 and 38.6 ± 12.8 years, respectively. Mean total dietary fructose intakes were 46.5 ± 24.5 (NF: 19.6 ± 10.7 and AF: 26.9 ± 13.9) and 37.3 ± 24.2 g/d (NF: 18.6 ± 10.5 and AF: 18.7 ± 13.6) in men and women, respectively. Compared with those in the lowest quartile of fructose intakes, men and women in the highest quartile, respectively, had 33% (95% CI, 1.15-1.47) and 20% (95% CI, 1.09-1.27) higher risk of the metabolic syndrome; 39% (CI, 1.16-1.63) and 20% (CI, 1.07-1.27) higher risk of abdominal obesity; 11% (CI, 1.02-1.17) and 9% (CI, 1.02-1.14) higher risk of hypertension; and 9% (CI, 1-1.15) and 9% (1.04-1.12) higher risk of impaired fasting glucose. Higher consumption of dietary fructose may have adverse metabolic effects.

  15. The role of GluN2A and GluN2B NMDA receptor subunits in AgRP and POMC neurons on body weight and glucose homeostasis.

    Science.gov (United States)

    Üner, Aykut; Gonçalves, Gabriel H M; Li, Wenjing; Porceban, Matheus; Caron, Nicole; Schönke, Milena; Delpire, Eric; Sakimura, Kenji; Bjørbæk, Christian

    2015-10-01

    Hypothalamic agouti-related peptide (AgRP) and pro-opiomelanocortin (POMC) expressing neurons play critical roles in control of energy balance. Glutamatergic input via n-methyl-d-aspartate receptors (NMDARs) is pivotal for regulation of neuronal activity and is required in AgRP neurons for normal body weight homeostasis. NMDARs typically consist of the obligatory GluN1 subunit and different GluN2 subunits, the latter exerting crucial differential effects on channel activity and neuronal function. Currently, the role of specific GluN2 subunits in AgRP and POMC neurons on whole body energy and glucose balance is unknown. We used the cre-lox system to genetically delete GluN2A or GluN2B only from AgRP or POMC neurons in mice. Mice were then subjected to metabolic analyses and assessment of AgRP and POMC neuronal function through morphological studies. We show that loss of GluN2B from AgRP neurons reduces body weight, fat mass, and food intake, whereas GluN2B in POMC neurons is not required for normal energy balance control. GluN2A subunits in either AgRP or POMC neurons are not required for regulation of body weight. Deletion of GluN2B reduces the number of AgRP neurons and decreases their dendritic length. In addition, loss of GluN2B in AgRP neurons of the morbidly obese and severely diabetic leptin-deficient Lep (ob/ob) mice does not affect body weight and food intake but, remarkably, leads to full correction of hyperglycemia. Lep (ob/ob) mice lacking GluN2B in AgRP neurons are also more sensitive to leptin's anti-obesity actions. GluN2B-containing NMDA receptors in AgRP neurons play a critical role in central control of body weight homeostasis and blood glucose balance via mechanisms that likely involve regulation of AgRP neuronal survival and structure, and modulation of hypothalamic leptin action.

  16. Pioglitazone is equally effective for diabetes prevention in older versus younger adults with impaired glucose tolerance.

    Science.gov (United States)

    Espinoza, Sara E; Wang, Chen-Pin; Tripathy, Devjit; Clement, Stephen C; Schwenke, Dawn C; Banerji, Mary Ann; Bray, George A; Buchanan, Thomas A; Henry, Robert R; Kitabchi, Abbas E; Mudaliar, Sunder; Stentz, Frankie B; Reaven, Peter D; DeFronzo, Ralph A; Musi, Nicolas

    2016-12-01

    To determine the efficacy of pioglitazone to prevent type 2 diabetes in older compared to younger adults with pre-diabetes. Six hundred two participants with impaired glucose tolerance (IGT) were randomized in double blind fashion to placebo or pioglitazone for diabetes prevention in the ACT NOW study (NEJM 364:1104-1115, 2011). Cox proportional hazard regression was used to compare time to development of diabetes over a mean of 2 years between older (≥61 years) and younger participants. We compared effects of pioglitazone versus placebo on metabolic profiles, inflammatory markers, adipokines, β cell function (disposition index), insulin sensitivity (Matsuda index), and body composition by ANOVA. Diabetes incidence was reduced by 85 % in older and 69 % in younger subjects (p = 0.41). β cell function (disposition index) increased by 35.0 % in the older and 26.7 % in younger subjects (p = 0.83). Insulin sensitivity (Matsuda index) increased by 3.07 (5.2-fold) in older and by 2.54 (3.8-fold) in younger participants (p = 0.58). Pioglitazone more effectively increased adiponectin in older versus younger subjects (22.9 ± 3.2 μg/mL [2.7-fold] vs. 12.7 ± 1.4 μg/mL [2.2-fold], respectively; p = 0.04). Younger subjects tended to have a greater increase in whole body fat mass compared to older subjects (3.6 vs. 3.1 kg; p = 0.061). Younger and older subjects had similar decreases in bone mineral density (0.018 ± 0.0071 vs. 0.0138 ± 0.021 g/cm 2 ). Younger and older pre-diabetic adults taking pioglitazone had similar reductions in conversion to diabetes and older adults had similar or greater improvements in metabolic risk factors, demonstrating that pioglitazone is useful in preventing diabetes in older adults.

  17. Short-term consumption of a plant protein diet does not improve glucose homeostasis of young C57BL/6J mice.

    Science.gov (United States)

    Lamming, Dudley W; Baar, Emma L; Arriola Apelo, Sebastian I; Tosti, Valeria; Fontana, Luigi

    2017-12-07

    Recently, it has become apparent that dietary macronutrient composition has a profound impact on metabolism, health and even lifespan. Work from many laboratories now suggest that dietary protein quality - the precise amino acid composition of the diet, as well as possibly the source of dietary protein - may also be critical in regulating the impact of diet on health. Perhaps in part due to the naturally low methionine content of plants, vegan diets are associated with a decreased risk of diabetes and improved insulin sensitivity, but this association is confounded by the lower overall protein intake of vegans. Here, we test the effect of consuming isocaloric rodent diets with similar amino acid profiles derived from either plant protein or dairy protein. We find that male C57BL/6J mice consuming either diet have similar glycemic control, as assessed by glucose, insulin, and pyruvate tolerance tests, and have similar overall body composition. We conclude that short-term feeding of plant protein has no positive or negative effect on the metabolic health of young male C57BL/6J mice, and suggest that dietary interventions that alter either dietary protein levels or the levels of specific essential amino acids are more likely to improve metabolic health than alterations in dietary protein source.

  18. Distribution of glucose transporters in renal diseases

    OpenAIRE

    Szablewski, Leszek

    2017-01-01

    Kidneys play an important role in glucose homeostasis. Renal gluconeogenesis prevents hypoglycemia by releasing glucose into the blood stream. Glucose homeostasis is also due, in part, to reabsorption and excretion of hexose in the kidney. Lipid bilayer of plasma membrane is impermeable for glucose, which is hydrophilic and soluble in water. Therefore, transport of glucose across the plasma membrane depends on carrier proteins expressed in the plasma membrane. In humans, there are three famil...

  19. Glucose homeostasis, insulin resistance and inflammatory biomarkers in patients with non-alcoholic fatty liver disease: Beneficial effects of supplementation with microalgae Chlorella vulgaris: A double-blind placebo-controlled randomized clinical trial.

    Science.gov (United States)

    Ebrahimi-Mameghani, Mehrangiz; Sadeghi, Zahra; Abbasalizad Farhangi, Mahdieh; Vaghef-Mehrabany, Elnaz; Aliashrafi, Soodabeh

    2017-08-01

    Chlorella vulgaris (C. vulgaris) is reported to improve dyslipidemia and hypertension; however, its effect on inflammatory biomarkers and insulin resistance has not been noticed thus far. Non-alcoholic fatty liver disease (NAFLD) as a hepatic symptom of metabolic syndrome is strongly associated with insulin resistance and inflammation. In the current interventional trial, we aimed to study the effects of C. vulgaris supplementation on glucose homeostasis, insulin resistance and inflammatory biomarkers in patients with NAFLD. Seventy NAFLD patients confirmed by ultra-sonographic findings were randomly assigned into intervention group (four 300 mg tablets of C. vulgaris) or placebo group (four 300 mg tablets of placebos) for 8 weeks. Anthropometric measurements, liver enzymes, fasting serum glucose (FSG), insulin, high sensitive C-reactive protein (hs-CRP) and tumor necrosis factor-alpha (TNF-α) were assessed and homeostatic model assessment (HOMA) score for insulin resistance was estimated before and after the intervention. Anthropometric measurements decreased significantly in both group (p vulgaris - treated group compared to placebo group. Serum concentrations of liver enzymes, FSG and hs-CRP also significantly decreased and serum insulin concentration and HOMA score increased significantly only in C. vulgaris-treated group (P vulgaris supplementation could be considered as an adjunctive therapy to decrease weight and improve glycemic status and reducing hs-CRP as well as improving liver function in patients with NAFLD. 201202233320N7. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  20. Gestational Protein Restriction Impairs Insulin-Regulated Glucose Transport Mechanisms in Gastrocnemius Muscles of Adult Male Offspring

    Science.gov (United States)

    Blesson, Chellakkan S.; Sathishkumar, Kunju; Chinnathambi, Vijayakumar

    2014-01-01

    Type II diabetes originates from various genetic and environmental factors. Recent studies showed that an adverse uterine environment such as that caused by a gestational low-protein (LP) diet can cause insulin resistance in adult offspring. The mechanism of insulin resistance induced by gestational protein restriction is not clearly understood. Our aim was to investigate the role of insulin signaling molecules in gastrocnemius muscles of gestational LP diet–exposed male offspring to understand their role in LP-induced insulin resistance. Pregnant Wistar rats were fed a control (20% protein) or isocaloric LP (6%) diet from gestational day 4 until delivery and a normal diet after weaning. Only male offspring were used in this study. Glucose and insulin responses were assessed after a glucose tolerance test. mRNA and protein levels of molecules involved in insulin signaling were assessed at 4 months in gastrocnemius muscles. Muscles were incubated ex vivo with insulin to evaluate insulin-induced phosphorylation of insulin receptor (IR), Insulin receptor substrate-1, Akt, and AS160. LP diet-fed rats gained less weight than controls during pregnancy. Male pups from LP diet–fed mothers were smaller but exhibited catch-up growth. Plasma glucose and insulin levels were elevated in LP offspring when subjected to a glucose tolerance test; however, fasting levels were comparable. LP offspring showed increased expression of IR and AS160 in gastrocnemius muscles. Ex vivo treatment of muscles with insulin showed increased phosphorylation of IR (Tyr972) in controls, but LP rats showed higher basal phosphorylation. Phosphorylation of Insulin receptor substrate-1 (Tyr608, Tyr895, Ser307, and Ser318) and AS160 (Thr642) were defective in LP offspring. Further, glucose transporter type 4 translocation in LP offspring was also impaired. A gestational LP diet leads to insulin resistance in adult offspring by a mechanism involving inefficient insulin-induced IR, Insulin receptor

  1. Acute and second-meal effects of almond form in impaired glucose tolerant adults: a randomized crossover trial

    Directory of Open Access Journals (Sweden)

    Considine Robert V

    2011-01-01

    Full Text Available Abstract Background Nut consumption may reduce the risk of developing type 2 diabetes. The aim of the current study was to measure the acute and second-meal effects of morning almond consumption and determine the contribution of different nut fractions. Methods Fourteen impaired glucose tolerant (IGT adults participated in a randomized, 5-arm, crossover design study where whole almonds (WA, almond butter (AB, defatted almond flour (AF, almond oil (AO or no almonds (vehicle - V were incorporated into a 75 g available carbohydrate-matched breakfast meal. Postprandial concentrations of blood glucose, insulin, non-esterified free fatty acids (NEFA, glucagon-like peptide-1 (GLP-1 and appetitive sensations were assessed after treatment breakfasts and a standard lunch. Results WA significantly attenuated second-meal and daylong blood glucose incremental area under the curve (AUCI and provided the greatest daylong feeling of fullness. AB and AO decreased blood glucose AUCI in the morning period and daylong blood glucose AUCI was attenuated with AO. WA and AO elicited a greater second-meal insulin response, particularly in the early postprandial phase, and concurrently suppressed the second-meal NEFA response. GLP-1 concentrations did not vary significantly between treatments. Conclusions Inclusion of almonds in the breakfast meal decreased blood glucose concentrations and increased satiety both acutely and after a second-meal in adults with IGT. The lipid component of almonds is likely responsible for the immediate post-ingestive response, although it cannot explain the differential second-meal response to AB versus WA and AO.

  2. Increased Brain Glucose Uptake After 12 Weeks of Aerobic High-Intensity Interval Training in Young and Older Adults.

    Science.gov (United States)

    Robinson, Matthew M; Lowe, Val J; Nair, K Sreekumaran

    2018-01-01

    Aerobic exercise training can increase brain volume and blood flow, but the impact on brain metabolism is less known. We determined whether high-intensity interval training (HIIT) increases brain metabolism by measuring brain glucose uptake in younger and older adults. Brain glucose uptake was measured before and after HIIT or a sedentary (SED) control period within a larger exercise study. Study procedures were performed at the Mayo Clinic in Rochester, MN. Participants were younger (18 to 30 years) or older (65 to 80 years) SED adults who were free of major medical conditions. Group sizes were 15 for HIIT (nine younger and six older) and 12 for SED (six younger and six older). Participants completed 12 weeks of HIIT or SED. HIIT was 3 days per week of 4 × 4 minute intervals at over 90% of peak aerobic capacity (VO2peak) with 2 days per week of treadmill walking at 70% VO2peak. Resting brain glucose uptake was measured using 18F-fluorodeoxyglucose positron emission tomography scans at baseline and at week 12. Scans were performed at 96 hours after exercise. VO2peak was measured by indirect calorimetry. Glucose uptake increased significantly in the parietal-temporal and caudate regions after HIIT compared with SED. The gains with HIIT were not observed in all brain regions. VO2peak was increased for all participants after HIIT and did not change with SED. We demonstrate that brain glucose metabolism increased after 12 weeks of HIIT in adults in regions where it is reduced in Alzheimer's disease. Copyright © 2017 Endocrine Society

  3. Protosappanin B protects PC12 cells against oxygen-glucose deprivation-induced neuronal death by maintaining mitochondrial homeostasis via induction of ubiquitin-dependent p53 protein degradation.

    Science.gov (United States)

    Zeng, Ke-Wu; Liao, Li-Xi; Zhao, Ming-Bo; Song, Fang-Jiao; Yu, Qian; Jiang, Yong; Tu, Peng-Fei

    2015-03-15

    Protosappanin B (PTB) is a bioactive dibenzoxocin derivative isolated from Caesalpinia sappan L. Here, we investigated the neuroprotective effects and the potential mechanisms of PTB on oxygen-glucose deprivation (OGD)-injured PC12 cells. Results showed that PTB significantly increased cell viability, inhibited cell apoptosis and up-regulated the expression of growth-associated protein 43 (a marker of neural outgrowth). Moreover, our study revealed that PTB effectively maintained mitochondrial homeostasis by up-regulation of mitochondrial membrane potential (MMP), inhibition of cytochrome c release from mitochondria and inactivation of mitochondrial caspase-9/3 apoptosis pathway. Further study showed that PTB significantly promoted cytoplasmic component degradation of p53 protein, a key negative regulator for mitochondrial function, resulting in a release of Bcl-2 from p53-Bcl-2 complex and an enhancing translocation of Bcl-2 to mitochondrial outer membrane. Finally, we found the degradation of p53 protein was induced by PTB via activation of a MDM2-dependent ubiquitination process. Taken together, our findings provided a new viewpoint of neuronal protection strategy for anoxia and ischemic injury with natural small molecular dibenzoxocin derivative by activating ubiquitin-dependent p53 protein degradation as well as increasing mitochondrial function. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Long-term impact of earthquake stress on fasting glucose control and diabetes prevalence among Chinese adults of Tangshan

    OpenAIRE

    An, Cuixia; Zhang, Yun; Yu, Lulu; Li, Na; Song, Mei; Wang, Lan; Zhao, Xiaochuan; Gao, Yuanyuan; Wang, Xueyi

    2014-01-01

    Objective: To investigate the long-term influence of stresses from the 1976 Tangshan earthquake on blood glucose control and the incidence of diabetes mellitus in Chinese people of Tangshan. Methods: 1,551 adults ≥ 37 years of age were recruited for this investigation in Tangshan city of China, where one of the deadliest earthquakes occurred in 1796. All subjects finished a questionnaire. 1,030 of them who experienced that earthquake were selected into the exposure group, while 521 were gathe...

  5. Clinical Use of Continuous Glucose Monitoring in Adults with Type 1 Diabetes.

    Science.gov (United States)

    Slattery, David; Choudhary, Pratik

    2017-05-01

    With the emphasis on intensive management of type 1 diabetes, data from studies support frequent monitoring of glucose levels to improve glycemic control and reduce glucose variability, which can be related to an increase in macro and microvascular complications. However, few perform capillary blood glucose that frequently. There are currently two available alternatives that this review will discuss, continuous glucose monitoring (CGM) and flash glucose monitoring. CGM has become an important diagnostic and therapeutic option in optimizing diabetes management. CGM systems are now more accurate, smaller, and easier to use compared to original models. Randomized controlled trials (RCTs) have demonstrated that CGM can improve Hemoglobin A1c (HbA1C) and reduce glucose variability in both continuous subcutaneous insulin infusion and multiple daily injection users. When used in an automated "insulin-suspend" system, reduced frequency of hypoglycemia and shorter time spent in hypoglycemic range have been demonstrated. Despite the potential benefits CGM has to offer in clinical practice, concerns exist on the accuracy of these devices and patient compliance with therapy, which may prevent the true clinical benefit of CGM being achieved, as observed in RCTs. Flash glucose monitoring systems FreeStyle ® Libre™ (Abbott Diabetes Care, Alameda, CA) are as accurate as many CGM systems available and have the added benefit of being factory calibrated. Studies have shown that flash glucose monitoring systems are very well tolerated by patients and effectively reduce glucose variability, increasing time in range.

  6. Bariatric surgery improves the cavernosal neuronal, vasorelaxation, and contraction mechanisms for erectile dysfunction as result of amelioration of glucose homeostasis in a diabetic rat model.

    Directory of Open Access Journals (Sweden)

    Yong Sun Choi

    Full Text Available Bariatric surgery is an effective treatment option for both obesity and obesity-related type 2 diabetes mellitus (T2DM. However, little is known regarding the effects of bariatric surgery on erectile dysfunction among patients with T2DM. Therefore, we investigated whether bariatric surgery would lead to structural and biochemical changes in the corpus cavernosum.Twenty-five male Otsuka Long-Evans Tokushima Fatty rats were assigned to either a control group (sham operation, n = 10 or a bariatric surgery group (gastric bypass surgery, n = 15. Four weeks after the operation, each group of rats was evaluated with an oral glucose tolerance test (OGTT. The penile intracavernous pressure was measured for erectile functional analysis. Histologic evaluation of the tissue was performed with Masson's trichrome staining. Endothelial nitric oxide synthase (eNOS, neuronal nitric oxide synthase (nNOS, Rho kinase, and 8-hydroxy-2-deoxyguanosine (8-OHdG levels in the corpus cavernosum were assayed by using western blot and ELISA.The mean body weight of the bariatric surgery group was lower than the control group (p = 0.002. The postoperative OGTT result was lower in the bariatric surgery group than in the control group (p = 0.014, and this was lower than the preoperative value (p = 0.037. The intracavernous pressure/mean arterial pressure ratio was higher in the bariatric surgery group compared to the control group (p = 0.021, and a higher cavernosum smooth muscle/collagen ratio was observed in the bariatric surgery group compared to the control group (p = 0.025. Likewise, the expression of eNOS and nNOS was higher in bariatric surgery group than in the control group (p = 0.027 and p = 0.008, respectively. Decreased expression of Rho kinase and levels of 8-OHdG were observed in the bariatric surgery group (p = 0.032.In this animal model, bariatric surgery appears to ameliorate T2DM-related metabolic dysfunction leading to

  7. Bariatric surgery improves the cavernosal neuronal, vasorelaxation, and contraction mechanisms for erectile dysfunction as result of amelioration of glucose homeostasis in a diabetic rat model.

    Science.gov (United States)

    Choi, Yong Sun; Lee, Sang Kuon; Bae, Woong Jin; Kim, Su Jin; Cho, Hyuk Jin; Hong, Sung-Hoo; Lee, Ji Youl; Hwang, Tae-Kon; Kim, Sae Woong

    2014-01-01

    Bariatric surgery is an effective treatment option for both obesity and obesity-related type 2 diabetes mellitus (T2DM). However, little is known regarding the effects of bariatric surgery on erectile dysfunction among patients with T2DM. Therefore, we investigated whether bariatric surgery would lead to structural and biochemical changes in the corpus cavernosum. Twenty-five male Otsuka Long-Evans Tokushima Fatty rats were assigned to either a control group (sham operation, n = 10) or a bariatric surgery group (gastric bypass surgery, n = 15). Four weeks after the operation, each group of rats was evaluated with an oral glucose tolerance test (OGTT). The penile intracavernous pressure was measured for erectile functional analysis. Histologic evaluation of the tissue was performed with Masson's trichrome staining. Endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), Rho kinase, and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels in the corpus cavernosum were assayed by using western blot and ELISA. The mean body weight of the bariatric surgery group was lower than the control group (p = 0.002). The postoperative OGTT result was lower in the bariatric surgery group than in the control group (p = 0.014), and this was lower than the preoperative value (p = 0.037). The intracavernous pressure/mean arterial pressure ratio was higher in the bariatric surgery group compared to the control group (p = 0.021), and a higher cavernosum smooth muscle/collagen ratio was observed in the bariatric surgery group compared to the control group (p = 0.025). Likewise, the expression of eNOS and nNOS was higher in bariatric surgery group than in the control group (p = 0.027 and p = 0.008, respectively). Decreased expression of Rho kinase and levels of 8-OHdG were observed in the bariatric surgery group (p = 0.032). In this animal model, bariatric surgery appears to ameliorate T2DM-related metabolic dysfunction leading to

  8. Mathematical Modelling of Glucose-Dependent Insulinotropic Polypeptide and Glucagon-like Peptide-1 following Ingestion of Glucose

    DEFF Research Database (Denmark)

    Røge, Rikke M; Bagger, Jonatan I; Alskär, Oskar

    2017-01-01

    The incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), play an important role in glucose homeostasis by potentiating glucose-induced insulin secretion. Furthermore, GLP-1 has been reported to play a role in glucose homeostasis by inhibiting ...

  9. Identification of Risk Factors Affecting Impaired Fasting Glucose and Diabetes in Adult Patients from Northeast China

    Directory of Open Access Journals (Sweden)

    Yutian Yin

    2015-10-01

    Full Text Available Background: Besides genetic factors, the occurrence of diabetes is influenced by lifestyles and environmental factors as well as trace elements in diet materials. Subjects with impaired fasting glucose (IFG have an increased risk of developing diabetes mellitus (DM. This study aimed to explore risk factors affecting IFG and diabetes in patients from Northeast China. Methods: A population-based, cross-sectional survey of chronic diseases and related risk factors was conducted in Jilin Province of Northeast China. All adult residents, aged 18–79, were invited to participate in this survey using the method of multistage stratified random cluster sampling. One hundred thirty-four patients with IFG or DM and 391 healthy control subjects were recruited. We compared demographic factors, body size measurements, healthy-related behaviors, and hair metallic element contents between IFG/diabetes patients and healthy individuals. Results: IFG/diabetes patients had a greater weight, waist, hip, and body mass index (BMI than control subjects. Significant differences in the content of zinc (Zn, potassium (K, copper (Ca, and sodium (Na as well as Cu/Zn ratios between IFG or DM patients and control subjects (p < 0.05 were also observed. Hair Cu, selenium (Se, and Na contents were positively correlated with blood glucose levels (Cu: rs = 0.135, p = 0.002; Se: rs = 0.110, p = 0.012; Na: rs = 0.091, p = 0.038. Polytomous logistic regression adjusting for age, sex, family history of diabetes and BMI, showed that subjects with high BMI were more likely to develop IFG and DM (IFG: OR = 1.15, OR 95% CI = 1.02–1.29; DM: OR = 1.15, OR 95% CI = 1.01–1.33. Moreover, rarely or never eating fruits was a risk factor for DM (OR = 5.46, OR 95% CI = 1.87–15.98 but not for IFG (OR = 1.70, OR 95% CI = 0.72–4.02. Subjects with abdominal obesity or DM history were more susceptible to DM (abdominal obesity: OR = 2.99, OR 95% CI = 1.07–8.37; DM history: OR = 2.69, OR 95

  10. Waist circumference as a predictor for blood glucose levels in adults

    Directory of Open Access Journals (Sweden)

    Shinta L Hardiman

    2016-02-01

    Full Text Available Anthropometric indexes such as body mass index (BMI, waist circumference (WC, hip ciucumference (HC, and waist–hip ratio (WHR, are all useful anthropometric measurements to provide important information on blood glucose concentrations. The aim of this study was to determine different anthropometric measurements, in particular BMI, waist circumference, hip circumference and waist-to-hip ratio, in their ability to predict the blood glucose levels in men and women 40 to 60. A cross-sectional study was conducted on a sample of 44 men and 127 women aged 40 to 50 who lived in Cipete Selatan subdistrict, South Jakarta. Blood glucose levels was assessed and anthropometric measurements comprising BMI, WC, HC, WHR were collected. Multiple linear regression analysis was used to determine the best predictor for blood glucose levels. The study showed that the prevalence of DM type 2 was 25.7% and the prevalence was higher in men (40.9% compared to women (23.5%. The significant predictive variables in the simple regression analysis were age and waist circumference. Multiple linear regression showed that after adjustment for age, WC was positively associated with blood glucose levels. Standardized a value was 0.172 (p=0.026. WC predict blood glucose levels, beyond that explained by traditional diabetic risk factors and BMI. These findings provide support for the recommendation that WC be a routine measure for identification of diabetes mellitus type 2 in men and women aged 40 to 60 years.

  11. Decreased regional cerebral glucose metabolism in the prefrontal regions in adults' with internet game addiction

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hyun Soo; Bang, Soong Ae; Yoon, Eun Jin; Cho, Sang Soo; Kim, Sang Hee; Kim, Yu Kyeong; Kim, Sang Eun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    Internet Game Addiction (IGA) is known to be associated with poor decision-making and diminished impulse control; however, the underlying neural substrates of IGA have not been identified. To investigate the neural substrates of IGA, we compared regional cerebral glucose metabolism between adults with and without IGA, primarily in the prefrontal brain regions, which have been implicated in inhibitory control. We studied 10 right-handed participants (5 controls: male, 23.8{+-}0.75 y, 5 IGAs: male, 22.6{+-}2.42 y) with FDG PET. A standardized questionnaire was used to assess the severity of IGA. Before scanning, all subjects carried out a computerized version of the Iowa Gambling Task (IGT) and the Balloon Analogue Risk Task (BART), as measures of behavioral inhibitory control. Statistical Parametric Mapping 2 (SPM2) was used to analyze differences in regional brain glucose metabolism between adults with and without IGA. Consistent with our predictions, compared to controls, significant reductions in FDG uptake in individuals with IGA were found in the bilateral orbitofrontal gyrus (BA 11, 47), bilateral inferior frontal gyrus (BA 44, 48), cingulate cortex (BA 24), and bilateral supplementary motor area (SMA) (BA 6); whereas increases were found in the bilateral hippocampus. Correlation analyses within the IGA group further showed that the level of glucose metabolism in the right orbitofrontal gyrus was marginally positively correlated with task scores in BART. Our results showed that IGA is associated with reduced glucose metabolism in the prefrontal regions involved in inhibitory control. This finding highlights dysfunctional inhibitory brain systems in individuals with IGA and offers implications for the development for therapeutic paradigms for IGA.

  12. Fast food consumption in Iranian adults; dietary intake and cardiovascular risk factors: Tehran Lipid and Glucose Study.

    Science.gov (United States)

    Bahadoran, Zahra; Mirmiran, Parvin; Golzarand, Mahdieh; Hosseini-Esfahani, Firoozeh; Azizi, Fereidoun

    2012-06-01

    Although fast food consumption has drastically increased in Iran in recent years; there is a paucity of data in relation to the association between fast food consumption, dietary intake, and cardiovascular risk factors. This study aims to determine fast food consumption status among young and middle-aged Iranian adults, and to assess its impact on dietary intake and cardiovascular disease (CVD) risk factors. This cross-sectional population-based study was conducted on 1944 young and middle-aged adults (840 men and 1104 women), who participated in the Tehran Lipid and Glucose Study (2006-2008). We collected dietary data by using a validated 168 item, semi-quantitative food frequency questionnaire. Total fast food consumption was calculated by summing up weekly consumption of the most commonly consumed fast foods in Iran. Mean consumption of fast food was 161g/week (95% CI: 147-175) for young adults and 108 g/week (95% CI: 101-115) for middle-aged adults. Mean dietary intakes of energy, fat, saturated fat, cholesterol, sodium, meat, and soft drinks increased significantly (P consumption decreased (P fast food in both age groups. In young adults, dietary energy density and protein intake increased significantly (P fast food tertiles (P fast food consumption and body mass index (BMI; β = 0.104; P consumption of fast foods is associated with poor dietary intake and some of the CVD risk factors in Iranian adults.

  13. Cranberry juice consumption lowers markers of cardiometabolic risk, including blood pressure and circulating C-reactive protein, triglyceride, and glucose concentrations in adults.

    Science.gov (United States)

    Novotny, Janet A; Baer, David J; Khoo, Christina; Gebauer, Sarah K; Charron, Craig S

    2015-06-01

    Cardiometabolic risk is the risk of cardiovascular disease (CVD), diabetes, or stroke, which are leading causes of mortality and morbidity worldwide. The objective of this study was to determine the potential of low-calorie cranberry juice (LCCJ) to lower cardiometabolic risk. A double-blind, placebo-controlled, parallel-arm study was conducted with controlled diets. Thirty women and 26 men (mean baseline characteristics: 50 y; weight, 79 kg; body mass index, 28 kg/m(2)) completed an 8-wk intervention with LCCJ or a flavor/color/energy-matched placebo beverage. Twice daily volunteers consumed 240 mL of LCCJ or the placebo beverage, containing 173 or 62 mg of phenolic compounds and 6.5 or 7.5 g of total sugar per 240-mL serving, respectively. Fasting serum triglycerides (TGs) were lower after consuming LCCJ and demonstrated a treatment × baseline interaction such that the participants with higher baseline TG concentrations were more likely to experience a larger treatment effect (1.15 ± 0.04 mmol/L vs. 1.25 ± 0.04 mmol/L, respectively; P = 0.027). Serum C-reactive protein (CRP) was lower for individuals consuming LCCJ than for individuals consuming the placebo beverage [ln transformed values of 0.522 ± 0.115 ln(mg/L) vs. 0.997 ± 0.120 ln(mg/L), P = 0.0054, respectively, and equivalent to 1.69 mg/L vs. 2.71 mg/L back-transformed]. LCCJ lowered diastolic blood pressure (BP) compared with the placebo beverage (69.2 ± 0.8 mm Hg for LCCJ vs. 71.6 ± 0.8 mm Hg for placebo; P = 0.048). Fasting plasma glucose was lower (P = 0.03) in the LCCJ group (5.32 ± 0.03 mmol/L) than in the placebo group (5.42 ± 0.03 mmol/L), and LCCJ had a beneficial effect on homeostasis model assessment of insulin resistance for participants with high baseline values (P = 0.035). LCCJ can improve several risk factors of CVD in adults, including circulating TGs, CRP, and glucose, insulin resistance, and diastolic BP. This trial was registered at clinicaltrials.gov as NCT01295684. © 2015

  14. Relationship of metabolic and endocrine parameters to brain glucose metabolism in older adults: do cognitively-normal older adults have a particular metabolic phenotype?

    Science.gov (United States)

    Nugent, S; Castellano, C A; Bocti, C; Dionne, I; Fulop, T; Cunnane, S C

    2016-02-01

    Our primary objective in this study was to quantify whole brain and regional cerebral metabolic rates of glucose (CMRg) in young and older adults in order to determine age-normalized reference CMRg values for healthy older adults with normal cognition for age. Our secondary objectives were to--(i) report a broader range of metabolic and endocrine parameters including body fat composition that could form the basis for the concept of a 'metabolic phenotype' in cognitively normal, older adults, and (ii) to assess whether medications commonly used to control blood lipids, blood pressure or thyroxine affect CMRg values in older adults. Cognition assessed by a battery of tests was normal for age and education in both groups. Compared to the young group (25 years old; n = 34), the older group (72 years old; n = 41) had ~14% lower CMRg (μmol/100 g/min) specifically in the frontal cortex, and 18% lower CMRg in the caudate. Lower grey matter volume and cortical thickness was widespread in the older group. These differences in CMRg, grey matter volume and cortical thickness were present in the absence of any known evidence for prodromal Alzheimer's disease (AD). Percent total body fat was positively correlated with CMRg in many brain regions but only in the older group. Before and after controlling for body fat, HOMA2-IR was significantly positively correlated to CMRg in several brain regions in the older group. These data show that compared to a healthy younger adult, the metabolic phenotype of a cognitively-normal 72 year old person includes similar plasma glucose, insulin, cholesterol, triglycerides and TSH, higher hemoglobin A1c and percent body fat, lower CMRg in the superior frontal cortex and caudate, but the same CMRg in the hippocampus and white matter. Age-normalization of cognitive test results is standard practice and we would suggest that regional CMRg in cognitively healthy older adults should also be age-normalized.

  15. Effects of exercise amount and intensity on abdominal obesity and glucose tolerance in obese adults: a randomized trial.

    Science.gov (United States)

    Ross, Robert; Hudson, Robert; Stotz, Paula J; Lam, Miu

    2015-03-03

    Exercise reduces obesity and related glucose tolerance, but whether increasing exercise intensity offers additional benefit at fixed exercise amounts is unknown. To determine the separate effects of exercise amount and intensity on abdominal obesity and glucose tolerance. 24-week, single-center, parallel-group trial from 2009 to 2013. (ClinicalTrials.gov: NCT00955071). Kingston, Ontario, Canada. 300 abdominally obese adults. Control (no exercise) (n = 75) or 5 weekly sessions of low-amount, low-intensity exercise (LALI) (180 and 300 kcal/session for women and men, respectively, at 50% of maximum oxygen consumption [V̇o2peak]) (n = 73); high-amount, low-intensity exercise (HALI) (360 and 600 kcal/session, respectively, at 50% of V̇o2peak) (n = 76); or high-amount, high-intensity exercise (HAHI) (360 and 600 kcal/session, respectively, at 75% of V̇o2peak) (n = 76). Daily unsupervised physical activity and sedentary time were measured by accelerometer. Waist circumference and 2-hour glucose level (primary outcomes) and cardiorespiratory fitness and measures of insulin action (secondary measurements). 217 participants (72.3%) completed the intervention. Mean exercise time in minutes per session was 31 (SD, 4.4) for LALI, 58 (SD, 7.6) for HALI, and 40 (SD, 6.2) for HAHI. Daily unsupervised physical activity and sedentary time did not change in any exercise group versus control (P > 0.33). After adjustment for age and sex in a linear mixed model, reductions in waist circumference were greater in the LALI (-3.9 cm [95% CI, -5.6 to -2.3 cm]; P exercise groups (P > 0.43). After adjustment for covariates, reductions in 2-hour glucose level were greater in the HAHI group (-0.7 mmol/L [-12.5 mg/dL] [CI, -1.3 to -0.1 mmol/L {-23.5 to -1.5 mg/dL}]; P = 0.027) than the control group but did not differ for the LALI or HALI group versus the control group (P > 0.159). Weight loss was greater in all exercise groups than the control group (P exercise groups (P > 0.182). The

  16. Three hours of intermittent hypoxia increases circulating glucose levels in healthy adults.

    Science.gov (United States)

    Newhouse, Lauren P; Joyner, Michael J; Curry, Timothy B; Laurenti, Marcello C; Man, Chiara Dalla; Cobelli, Claudio; Vella, Adrian; Limberg, Jacqueline K

    2017-01-01

    An independent association exists between sleep apnea and diabetes. Animal models suggest exposure to intermittent hypoxia, a consequence of sleep apnea, results in altered glucose metabolism and fasting hyperglycemia. However, it is unknown if acute exposure to intermittent hypoxia increases glucose concentrations in nondiabetic humans. We hypothesized plasma glucose would be increased from baseline following 3 h of intermittent hypoxia in healthy humans independent of any effect on insulin sensitivity. Eight (7M/1F, 21-34 years) healthy subjects completed two study visits randomized to 3 h of intermittent hypoxia or continuous normoxia, followed by an oral glucose tolerance test. Intermittent hypoxia consisted of 25 hypoxic events per hour where oxygen saturation (SpO 2 ) was significantly reduced (Normoxia: 97 ± 1%, Hypoxia: 90 ± 2%, P  0.05). In contrast, circulating glucose concentrations were increased after 3 h of intermittent hypoxia when compared to baseline (5.0 ± 0.2 vs. 5.3 ± 0.2 mmol/L, P = 0.01). There were no detectable changes in insulin sensitivity following intermittent hypoxia when compared to continuous normoxia, as assessed by the oral glucose tolerance test (P > 0.05). Circulating glucose is increased after 3 h of intermittent hypoxia in healthy humans, independent of any lasting changes in insulin sensitivity. These novel findings could explain, in part, the high prevalence of diabetes in patients with sleep apnea and warrant future studies to identify underlying mechanisms. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  17. Glucose hypometabolism is highly localized, but lower cortical thickness and brain atrophy are widespread in cognitively normal older adults.

    Science.gov (United States)

    Nugent, Scott; Castellano, Christian-Alexandre; Goffaux, Philippe; Whittingstall, Kevin; Lepage, Martin; Paquet, Nancy; Bocti, Christian; Fulop, Tamas; Cunnane, Stephen C

    2014-06-01

    Several studies have suggested that glucose hypometabolism may be present in specific brain regions in cognitively normal older adults and could contribute to the risk of subsequent cognitive decline. However, certain methodological shortcomings, including a lack of partial volume effect (PVE) correction or insufficient cognitive testing, confound the interpretation of most studies on this topic. We combined [(18)F]fluorodeoxyglucose ([(18)F]FDG) positron emission tomography (PET) and magnetic resonance (MR) imaging to quantify cerebral metabolic rate of glucose (CMRg) as well as cortical volume and thickness in 43 anatomically defined brain regions from a group of cognitively normal younger (25 ± 3 yr old; n = 25) and older adults (71 ± 9 yr old; n = 31). After correcting for PVE, we observed 11-17% lower CMRg in three specific brain regions of the older group: the superior frontal cortex, the caudal middle frontal cortex, and the caudate (P ≤ 0.01 false discovery rate-corrected). In the older group, cortical volumes and cortical thickness were 13-33 and 7-18% lower, respectively, in multiple brain regions (P ≤ 0.01 FDR correction). There were no differences in CMRg between individuals who were or were not prescribed antihypertensive medication. There were no significant correlations between CMRg and cognitive performance or metabolic parameters measured in fasting plasma. We conclude that highly localized glucose hypometabolism and widespread cortical thinning and atrophy can be present in older adults who are cognitively normal, as assessed using age-normed neuropsychological testing measures. Copyright © 2014 the American Physiological Society.

  18. Secretory granule neuroendocrine protein 1 (SGNE1 genetic variation and glucose intolerance in severe childhood and adult obesity

    Directory of Open Access Journals (Sweden)

    Charpentier Guillaume

    2007-07-01

    Full Text Available Abstract Background 7B2 is a regulator/activator of the prohormone convertase 2 which is involved in the processing of numerous neuropeptides, including insulin, glucagon and pro-opiomelanocortin. We have previously described a suggestive genetic linkage peak with childhood obesity on chr15q12-q14, where the 7B2 encoding gene, SGNE1 is located. The aim of this study is to analyze associations of SGNE1 genetic variation with obesity and metabolism related quantitative traits. Methods We screened SGNE1 for genetic variants in obese children and genotyped 12 frequent single nucleotide polymorphisms (SNPs. Case control analyses were performed in 1,229 obese (534 children and 695 adults, 1,535 individuals with type 2 diabetes and 1,363 controls, all French Caucasians. We also studied 4,922 participants from the D.E.S.I.R prospective population-based cohort. Results We did not find any association between SGNE1 SNPs and childhood or adult obesity. However, the 5' region SNP -1,701A>G associated with higher area under glucose curve after oral glucose tolerance test (p = 0.0005, higher HOMA-IR (p = 0.005 and lower insulinogenic index (p = 0.0003 in obese children. Similar trends were found in obese adults. SNP -1,701A>G did not associate with risk of T2D but tends to associate with incidence of type 2 diabetes (HR = 0.75 95%CI [0.55–1.01]; p = 0.06 in the prospective cohort. Conclusion SGNE1 genetic variation does not contribute to obesity and common forms of T2D but may worsen glucose intolerance and insulin resistance, especially in the background of severe and early onset obesity. Further molecular studies are required to understand the molecular bases involved in this process.

  19. Restraint Stress Impairs Glucose Homeostasis Through Altered ...

    African Journals Online (AJOL)

    olayemitoyin

    serum level of adiponectin was significantly (p< 0.05) lower compared with ... were significantly (p< 0.05) decreased in the skeletal muscle of restraint stress exposed rats. ... controlled conditions for the light/dark cycle, ..... increase the production of catecholamines. ... specific protein that has been suggested to play a role.

  20. Impact of PTBP1 rs11085226 on glucose-stimulated insulin release in adult Danes

    DEFF Research Database (Denmark)

    Hansen, Tue Haldor; Vestergaard, Henrik; Jørgensen, Torben

    2015-01-01

    ,641 glucose tolerant controls, respectively. Quantitative trait analyses were performed in up to 13,605 individuals subjected to an OGTT or blood samples obtained after an overnight fast, as well as in 596 individuals subjected to an IVGTT. Results: Analyses of fasting and OGTT-derived quantitative traits did.......024; P=0.01) assuming a dominant model of inheritance, but failed to replicate a previously reported association with area under the curve (AUC) for insulin. Case control analysis did not show an association of the PTBP1 rs11085226 variant with type 2 diabetes. Conclusions: Despite failure to replicate......Background: The variant rs11085226 (G) within the gene encoding polypyrimidine tract binding protein 1 (PTBP1) was reported to associate with reduced insulin release determined by an oral glucose tolerance test (OGTT) as well as an intravenous glucose tolerance test (IVGTT). The aim of the present...

  1. Effect of metformin on substrate utilization after exercise training in adults with impaired glucose tolerance.

    Science.gov (United States)

    Malin, Steven K; Braun, Barry

    2013-04-01

    Metformin attenuates the higher insulin sensitivity that occurs with exercise training. Sixteen people with prediabetes trained for 10 weeks while taking metformin (n = 8) or placebo (n = 8). Substrate utilization was assessed using glucose kinetics and indirect calorimetry. After training, exercise whole-body fat oxidation was higher and glycogen use lower (p use was unchanged. Training-induced enhancement of insulin sensitivity (clamp) correlated with higher peak oxygen uptake (r = 0.70; p < 0.05), but was independent of glucose kinetic and substrate metabolism.

  2. Association between whole blood mercury and glucose intolerance among adult Inuit in Greenland

    DEFF Research Database (Denmark)

    Jeppesen, Charlotte; Valera, Beatriz; Nielsen, Nina O

    2015-01-01

    OBJECTIVES: The Arctic diet is partly constituted by traditional food characterized by top predator animals such as whales, walrus, and seals with high mercury content. Mercury exposure has been associated with glucose intolerance in Western populations. We studied the association between whole...

  3. Prevalence and associated factors of diabetes and impaired fasting glucose in Chinese hypertensive adults aged 45 to 75 years.

    Directory of Open Access Journals (Sweden)

    Xianhui Qin

    Full Text Available This study examined the prevalence of impaired fasting glucose (IFG and diabetes and their associated factors in 17,184 Chinese hypertensive adults aged 45-75 years.A cross-sectional investigation was carried out in a rural area of Lianyungang, China. Previously undiagnosed diabetes [fasting plasma glucose (FPG ≥ 7.0 mmol/l] and IFG (6.1-6.9 mmol/l were defined based on FPG concentration. Previously diagnosed diabetes was determined on the basis of self-report. Total diabetes included both previously diagnosed diabetes and previously undiagnosed diabetes.The prevalence of previously diagnosed diabetes, undiagnosed diabetes, and IFG were 3.4%, 9.8%, and 14.1%, respectively. About 74.2% of the participants with diabetes had not previously been diagnosed. In the multivariable logistic-regression model, older age, men, antihypertensive treatment, obesity (BMI ≥ 25 kg/m(2, abdominal obesity (waist circumference ≥ 90 cm for men and ≥ 80 cm for women, non-current smoking, a family history of diabetes, higher heart rate, lower physical activity levels, and inland residence (versus coastal were significantly associated with both total diabetes and previously undiagnosed diabetes. Furthermore, methylene- tetrahydrofolate reductase (MTHFR 677 TT genotype was an independent associated factor for total diabetes, and current alcohol drinking was an independent associated factor for previously undiagnosed diabetes. At the same time, older age, men, abdominal obesity, non-current smoking, current alcohol drinking, a family history of diabetes, higher heart rate, and inland residence (versus coastal were important independent associated factors for IFG.In conclusion, we found a high prevalence of diabetes in Chinese hypertensive adults. Furthermore, about three out of every four diabetic adults were undiagnosed. Our results suggest that population-level measures aimed at the prevention, identification (even if only based on the FPG evaluation, and

  4. Compound- and sex-specific effects on programming of energy and immune homeostasis in adult C57BL/6JxFVB mice after perinatal TCDD and PCB 153

    Energy Technology Data Exchange (ETDEWEB)

    Esterik, J.C.J. van, E-mail: joantine.van.esterik@rivm.nl [Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven (Netherlands); Department of Chemistry and Biology, Institute for Environmental Studies (IVM), VU University, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands); Verharen, H.W., E-mail: henny.verharen@rivm.nl [Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven (Netherlands); Hodemaekers, H.M., E-mail: hennie.hodemaekers@rivm.nl [Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven (Netherlands); Gremmer, E.R., E-mail: eric.gremmer@rivm.nl [Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven (Netherlands); Nagarajah, B., E-mail: bhawani.nagarajah@rivm.nl [Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven (Netherlands); Kamstra, J.H., E-mail: jorke.kamstra@vu.nl [Department of Chemistry and Biology, Institute for Environmental Studies (IVM), VU University, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands); Dollé, M.E.T., E-mail: martijn.dolle@rivm.nl [Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven (Netherlands); Legler, J., E-mail: juliette.legler@vu.nl [Department of Chemistry and Biology, Institute for Environmental Studies (IVM), VU University, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands); Ven, L.T.M. van der, E-mail: leo.van.der.ven@rivm.nl [Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven (Netherlands)

    2015-12-01

    Early life exposure to endocrine disrupting compounds has been linked to chronic diseases later in life, like obesity and related metabolic disorders. We exposed C57BL/6JxFVB hybrid mice to the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the constitutive androstane receptor/pregnane X receptor agonist polychlorinated biphenyl 153 (PCB 153) in an experimental design relevant for human exposure. Exposure occurred during gestation and lactation via maternal feed to a wide dose range (TCDD: 10–10,000 pg/kg body weight/day; PCB 153: 0.09–1406 μg/kg body weight/d). Then exposure was ceased and offspring were followed up to 1 year of age. Metabolic parameters like body weight, fat pad weights, glucose tolerance, endocrine serum profile, and neurobehavioral and immunological parameters were determined. Body weight was transiently affected by both compounds throughout the follow-up. TCDD-exposed males showed decreased fat pad and spleen weights and an increase in IL-4 production of splenic immune cells. In contrast, females showed increased fat pad weights and production of IFNγ. PCB 153-exposed males showed an increase in glucose, whereas females showed an increase in glucagon, a decrease in pancreas weight, and an increase in thymus weight. In conclusion, early life exposure to TCDD appears to affect programming of energy and immune homeostasis in offspring, whereas the effects of perinatal PCB 153 were mainly on programming of glucose homeostasis. Both compounds act sex-specifically. Lowest derived BMDLs (lower bounds of the (two sided) 90%-confidence interval for the benchmark dose) for both compounds are not lower than current tolerable daily intakes. - Highlights: • Early life exposure to TCDD affects programming of energy and immune homeostasis. • Early life exposure to PCB 153 affects programming of energy homeostasis. • Both compounds act sex-specifically. • Lowest derived BMDLs for both TCDD and PCB 153 are not

  5. Compound- and sex-specific effects on programming of energy and immune homeostasis in adult C57BL/6JxFVB mice after perinatal TCDD and PCB 153

    International Nuclear Information System (INIS)

    Esterik, J.C.J. van; Verharen, H.W.; Hodemaekers, H.M.; Gremmer, E.R.; Nagarajah, B.; Kamstra, J.H.; Dollé, M.E.T.; Legler, J.; Ven, L.T.M. van der

    2015-01-01

    Early life exposure to endocrine disrupting compounds has been linked to chronic diseases later in life, like obesity and related metabolic disorders. We exposed C57BL/6JxFVB hybrid mice to the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the constitutive androstane receptor/pregnane X receptor agonist polychlorinated biphenyl 153 (PCB 153) in an experimental design relevant for human exposure. Exposure occurred during gestation and lactation via maternal feed to a wide dose range (TCDD: 10–10,000 pg/kg body weight/day; PCB 153: 0.09–1406 μg/kg body weight/d). Then exposure was ceased and offspring were followed up to 1 year of age. Metabolic parameters like body weight, fat pad weights, glucose tolerance, endocrine serum profile, and neurobehavioral and immunological parameters were determined. Body weight was transiently affected by both compounds throughout the follow-up. TCDD-exposed males showed decreased fat pad and spleen weights and an increase in IL-4 production of splenic immune cells. In contrast, females showed increased fat pad weights and production of IFNγ. PCB 153-exposed males showed an increase in glucose, whereas females showed an increase in glucagon, a decrease in pancreas weight, and an increase in thymus weight. In conclusion, early life exposure to TCDD appears to affect programming of energy and immune homeostasis in offspring, whereas the effects of perinatal PCB 153 were mainly on programming of glucose homeostasis. Both compounds act sex-specifically. Lowest derived BMDLs (lower bounds of the (two sided) 90%-confidence interval for the benchmark dose) for both compounds are not lower than current tolerable daily intakes. - Highlights: • Early life exposure to TCDD affects programming of energy and immune homeostasis. • Early life exposure to PCB 153 affects programming of energy homeostasis. • Both compounds act sex-specifically. • Lowest derived BMDLs for both TCDD and PCB 153 are not

  6. Greater Glycaemic Response to an Oral Glucose Load in Healthy, Lean, Active and Young Chinese Adults Compared to Matched Caucasians

    Directory of Open Access Journals (Sweden)

    Trevor Simper

    2018-04-01

    Full Text Available There are ethnic differences recorded in glycaemic response and rates of type 2 diabetes mellitus (DM between Chinese and Caucasian populations. Whether these differences are evident in matched healthy, lean, active, young adults is unclear. This study compares the postprandial glycaemic response of a group of Chinese participants (n = 49 with a group of similar Caucasians, (n = 48 aged 23.8 (±4.35 years, body mass index (BMI 22.7 (±2.6 kg/m2, healthy (free from non-communicable disease, and lean (body fat % 23.28% (±5.04. Participants undertook an oral glucose tolerance test to identify any significant differences in postprandial blood glucose response. Body fat percentage, body mass, age, physical activity, baseline glucose and HbA1c did not significantly differ between groups. Data from food frequency questionnaires indicated that the Chinese participants consumed less starchy foods, candy and “other” sweets and sugary drinks, and more rice than the Caucasians (all p ≤ 0.001, but not a greater overall intake of carbohydrates or any other macronutrient (all p > 0.05. The two groups’ postprandial blood glucose responses and 2-h incremental area under the curve values (iAUC—156.67 (74.12 mmol/L 120 min for Caucasians versus 214.03 (77.49 mmol/L 120 min for Chinese—indicate significant differences (p = 0.003 and p < 0.001 respectively between groups. Findings suggest that the difference between the two groups’ iAUC values do not relate to obvious lifestyle factors. The Chinese group were eating the least sugary and starchy food but had the highest iAUC. It is argued that the Chinese group in this investigation have the most favourable BMI, body fat percentage, and body mass, yet “poorest” glycaemic response.

  7. Effects of indigestible carbohydrates in barley on glucose metabolism, appetite and voluntary food intake over 16 h in healthy adults.

    Science.gov (United States)

    Johansson, Elin V; Nilsson, Anne C; Östman, Elin M; Björck, Inger M E

    2013-04-11

    Recent knowledge in animals suggests that gut microbial metabolism may affect host metabolism, including appetite regulating hormones. The aim of the present study was to evaluate the potential effects of a whole grain barley kernel product, rich in intrinsic indigestible carbohydrates (dietary fibre and resistant starch), on markers of metabolism and appetite regulation in healthy subjects. Boiled barley kernels (BK) or white wheat bread (WWB; reference) were provided as late evening meals to 19 young adults in random order using a cross-over design. During subsequent ad libitum standardized breakfast and lunch meals (10.5-16 h), blood was collected for analysis of glucose, plasma insulin, adiponectin, ghrelin, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), serum free fatty acids (FFA) and interleukin (IL)-6. In addition, appetite sensations, voluntary energy intake and breath H2 were determined. BK as evening meal increased plasma GLP-1 at fasting (P < 0.05) and during the experimental day (P < 0.01) compared with WWB. In addition the BK evening meal decreased fasting serum FFA (P < 0.05) and tended to decrease fasting serum IL-6 (P = 0.06). At lunch, preceded by BK evening meal, voluntary energy intake was decreased (P < 0.05) when compared to WWB evening meal. The BK evening meal decreased incremental blood glucose area (P < 0.01), promoted higher breath H2 (P < 0.001), maintained adiponectin concentrations (P < 0.05) and reduced perceived hunger (P < 0.05) during 10.5-16 h after the meal. The results indicate that the BK evening meal, facilitate glucose regulation, increase the release of GLP-1, reduce subsequent energy intake while at the same time decreasing hunger over 2 subsequent meals, and reduce fasting FFA the subsequent morning, possibly mediated through gut microbial fermentation of the indigestible carbohydrates.

  8. Interaction between VEGF receptor-2 gene polymorphisms and dietary patterns on blood glucose and lipid levels in Chinese Malaysian adults.

    Science.gov (United States)

    Yap, Roseline Wai Kuan; Shidoji, Yoshihiro; Hon, Wei Min; Masaki, Motofumi

    2011-01-01

    The prevalence of lifestyle-related chronic diseases is increasing and gene-diet interaction studies are limited among the Malaysian population. This study was conducted to evaluate the association and interaction effects of vascular endothelial growth factor receptor-2(VEGFR2) gene polymorphisms and dietary patterns on anthropometric and biochemical risk factors of chronic diseases in 179 Chinese Malaysian adults. Genotyping of rs1870377 and rs2071559 was performed by real-time PCR using TaqMan probes. Dietary patterns were constructed from the food frequency questionnaire using factor analysis. Anthropometric measurements: body mass index (BMI), systolic and diastolic blood pressure and biomarkers: blood glucose, glycated hemoglobin A1c (HbA1c) and lipids were obtained. Two dietary patterns: 'Balanced diet' and 'Meat, rice and noodles diet' (MRND) were extracted. MRND was associated with higher BMI, blood pressure, blood glucose and lipids, while T alleles in both rs1870377 and rs2071559 were associated with higher blood lipids (p Malaysian adults. Copyright © 2012 S. Karger AG, Basel.

  9. Prevalence of Non-responders for Glucose Control Markers after 10 Weeks of High-Intensity Interval Training in Adult Women with Higher and Lower Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Cristian Álvarez

    2017-07-01

    Full Text Available Background: Exercise training improves performance and biochemical parameters on average, but wide interindividual variability exists, with individuals classified as responders (R or non-responders (NRs, especially between populations with higher or lower levels of insulin resistance. This study assessed the effects of high-intensity interval training (HIIT and the prevalence of NRs in adult women with higher and lower levels of insulin resistance.Methods: Forty adult women were assigned to a HIIT program, and after training were analyzed in two groups; a group with higher insulin resistance (H-IR, 40 ± 6 years; BMI: 29.5 ± 3.7 kg/m2; n = 20 and a group with lower insulin resistance (L-IR, 35 ± 9 years; 27.8 ± 2.8 kg/m2; n = 20. Anthropometric, cardiovascular, metabolic, and performance variables were measured at baseline and after 10 weeks of training.Results: There were significant training-induced changes [delta percent (Δ%] in fasting glucose, fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR scores in the H-IR group (−8.8, −26.5, −32.1%, p < 0.0001, whereas no significant changes were observed in the L-IR. Both groups showed significant pre-post changes in other anthropometric variables [waist circumference (−5.2, p < 0.010, and −3.8%, p = 0.046 and tricipital (−13.3, p < 0.010, and −13.6%, p < 0.0001, supra-iliac (−19.4, p < 0.0001, and −13.6%, p < 0.0001, and abdominal (−18.2, p < 0.0001, and −15.6%, p < 0.010 skinfold measurements]. Systolic blood pressure decreased significantly only in the L-IR group (−3.2%, p < 0.010. Both groups showed significant increases in 1RMLE (+12.9, p < 0.010, and +14.7%, p = 0.045. There were significant differences in the prevalence of NRs between the H-IR and L-IR groups for fasting glucose (25 vs. 95%, p < 0.0001 and fasting insulin (p = 0.025 but not for HOMA-IR (25 vs. 45%, p = 0.185.Conclusion: Independent of the “magnitude” of the

  10. Effect of food deprivation and hormones of glucose homeostasis on the acetyl CoA carboxylase activity in mouse brain: a potential role of acc in the regulation of energy balance

    Directory of Open Access Journals (Sweden)

    Mukherjee Amrita

    2006-02-01

    Full Text Available Abstract We studied the regulation of brain acetyl CoA carboxylase (ACC activity during food deprivation and under the influence of hormones of glucose homeostasis: glucagon and insulin. Mice were deprived of food and water for time periods of 1, 3, 6, 9, 12 and 24 hours and were then allowed to re-feed for 5, 30 and 60 minutes. Mice that were deprived for up to 6 h, and then re-fed for 60 min, consumed the same amount of food compared to the ad libitum (control animals. However, after 9 h of deprivation, mice consumed only 50% of food present even after 1 h of re-feeding, compared to the controls. The ACC activity was measured in the whole mouse brain of controls and after 1, 3, 6, 9, 12, and 24 h of food deprivation. Brain extracts assayed from control mice expressed an ACC activity of 0.988 ± 0.158 fmol/min/mg tissue without citrate and 0.941 ± 0.175 fmol/min/mg tissue with citrate. After 1 h of food deprivation, the total ACC activity without citrate decreased to 0.575 ± 0.087 fmol/min/mg and in the presence of citrate, 0.703 ± 0.036 fmol/min/mg activity was measured. The citrate-dependent ACC activity decreased over time, with only 0.478 ± 0.117 fmol/min/mg of activity remaining after 24 h. Intraperitoneal (i.p. injections of insulin, glucagon and phosphate buffered saline (PBS were performed and whole brain ACC activity measured. After hormone administration, there were no significant differences in ACC activity in the presence of citrate. However, in the absence of citrate, there was a significant 20% decrease in ACC activity with glucagon (1.36 ± 0.09 fmol/min/mg and a 33% increase with insulin (2.49 ± 0.11 fmol/min/mg injections compared to PBS controls (1.67 ± 0.08 fmol/min/mg. Neuropeptide Y (NPY levels of corresponding brain extracts were measured by ELISA (OD using anti-NPY antibody and showed an 18% decrease upon insulin injection (0.093 ± 0.019 and a 50% increase upon glucagon injection (0.226 ± 0.084 as compared to

  11. Association of Genetic Loci With Glucose Levels in Childhood and Adolescence A Meta-Analysis of Over 6,000 Children

    DEFF Research Database (Denmark)

    Barker, A.; Sharp, S. J.; Timpson, N. J.

    2011-01-01

    with fasting glucose were genotyped in six studies of children and adolescents of European origin, including over 6,000 boys and girls aged 9-16 years. We performed meta-analyses to test associations of individual SNPs and a weighted risk score of the 16 loci with fasting glucose. RESULTS-Nine loci were...... glucose loci. Children and adolescents carrying glucose-raising alleles of G6PC2, MTNR1B, GCK, and GLIS3 also showed reduced p-cell function, as indicated by homeostasis model assessment of beta-cell function. Analysis using a weighted risk score showed an increase [beta (95% CI)] in fasting glucose level....... In nondiabetic adults, fasting glucose changes little over time, and our results suggest that age-independent effects of fasting glucose loci contribute to long-term interindividual differences in glucose levels from childhood onwards. Diabetes 60:1805-1812, 2011...

  12. Exercise effects on fitness, lipids, glucose tolerance and insulin levels in young adults.

    Science.gov (United States)

    Israel, R G; Davidson, P C; Albrink, M J; Krall, J M

    1981-07-01

    The effect of 3 different physical training programs on cardiorespiratory (cr) fitness, fasting plasma lipids, glucose and insulin levels, and scapular skinfold thickness was assessed in 64 healthy college men. Training sessions were held 4 times a week for 5 weeks. The cr fitness improved significantly and skinfold thickness decreased following the aerobic, the pulse workout (interval training), and the anaerobic training compared to the control group. Skinfold thickness, plasma insulin, and triglyceride concentrations were significantly intercorrelated before and after training. The exercise programs had no significant effect on plasma cholesterol, triglycerides, phospholipids, glucose tolerance, or insulin levels. Change in adipose mass was thus dissociated from change in plasma insulin and triglyceride concentrations. It was concluded that in young men plasma triglycerides, the lipid component mostly readily reduced by exercise, were too low to be reduced further by a physical training program.

  13. The rate of cerebral utilization of glucose, ketone bodies, and oxygen: a comparative in vivo study of infant and adult rats.

    Science.gov (United States)

    Dahlquist, G; Persson, B

    1976-11-01

    Cerebral blood flow (CBF) was measured by means of Celabeled microspheres in infant (20-day-old) and adult (3-month-old) rats, anesthetised with Na-5-ethyl-5-(1-methylpropyl)2-thiobarbituric acid. Cerebral arteriovenous differences of acetoacetate, D-beta-hydroxybutyrate, glucose, lactate, and oxygen and brain DNA content were determined in other groups of similarly treated infant and adult animals fed or starved for 48 or 72 hr. The mean CBF values of 0.48+/-0.04 and 0.62+/-0.07 ml/(g X min), +/- SEM, in infant and adult animals, respectively, were not significantly different. CBF was unaffected by starvation. At any given arterial concentration the cerebral arteriovenous difference of acetoacetate was significantly higher in infant than adult rats. The same was true for D-beta-hydroxybutyrate at arterial concentrations above 1 mmol/liter. There was an approximately linear relationship between arterial concentration of acetoacetate and its cerebral arteriovenous difference in both infant and adult rats. A similar relationship was found for D-beta-hydroxybutyrate only in infant animals. In the fed state, the cerebral uptake of glucose and ketone bodies (micromoles per (mg DNA X min)) was not different in infant and adult rats. During starvation, cerebral uptake of ketone bodies expressed as micromoles per (mg DNA X min) was higher in infant than adult rats, indicating a higher rate of utilization of ketone bodies per cell in these animals. For glucose, no such difference was found in either fed or starved groups (Table 3). The average percentage of the total cerebral uptake of substrates (micromoles per min) accounted for by ketone bodies increased in both infant and adult rats during starvation. This percentage value was clearly higher in infant than adult rats during starvation. After 72 hr of starvation the values were 38.8% and 15.2% in infant and adult rats, respectively (Fig. 3). Calculated cerebral metabolic rate for oxygen (CMRO2), assuming complete

  14. Insulin resistance, β-cell dysfunction and differences in curves of plasma glucose and insulin in the intermediate points of the standard glucose tolerance test in adults with cystic fibrosis.

    Science.gov (United States)

    Cano Megías, Marta; González Albarrán, Olga; Guisado Vasco, Pablo; Lamas Ferreiro, Adelaida; Máiz Carro, Luis

    2015-02-01

    diabetes has become a co-morbidity with a negative impact on nutritional status, lung function and survival in cystic fibrosis. To identify any changes in intermediate points after a 2-hour oral glucose tolerance test (OGTT), pancreatic β-cell dysfunction, and insulin resistance in cystic fibrosis-related diabetes. It was carried out a retrospective analysis in a cohort of 64 patients affected of cystic fibrosis, older than 14 years, using the first pathological OGTT. Peripheral insulin resistance was measured using the homeostasis model assessment for insulin resistance (HOMA- IR), and pancreatic β-cell function was calculated according to Wareham. Time to maximum plasma insulin and glucose levels and area under the curve (AUC0-120) were also measured. Twenty-eight women and 36 men with a mean age of 26.8 years were enrolled, of whom 26.7% had normal glucose tolerance (NGT), 18.3% cystic fibrosis-related diabetes without fasting hyperglycemia (CFRD w/o FPG), 10% indeterminate (INDET), and 45% impaired glucose tolerance (IGT). HOMA-IR values were not significantly different between the diagnostic categories. Patients with any pathological change had worse β cell function, with a significant delay in insulin secretion, although there were no differences in total insulin production (AUC0-120). Time to maximum glucose levels was significantly shorter in NGT patients as compared to other categories, with glucose AUC0-120 being higher in the different diagnostic categories as compared to NGT. In over half the cases, peak blood glucose levels during a standard OGTT are reached in the intermediate time points, rather than at the usual time of 120minutes. Patients with cystic fibrosis and impaired glucose metabolism have a delayed insulin secretion during the standard OGTT due to loss of first-phase insulin secretion, with no differences in total insulin production. Absence of significant changes in HOMA-IR suggests that β-cell dysfunction is the main pathogenetic

  15. The association between Western and Prudent dietary patterns and fasting blood glucose levels in type 2 diabetes and normal glucose metabolism in older Australian adults.

    Science.gov (United States)

    Walsh, Erin I; Jacka, Felice N; Butterworth, Peter; Anstey, Kaarin J; Cherbuin, Nicolas

    2017-06-01

    High blood glucose and type 2 diabetes are associated with a range of adverse health and cognitive outcomes. One factor that contributes to high blood glucose and type 2 diabetes is dietary intake. This study investigated the relationship between dietary patterns, fasting blood glucose and diabetes status in a sample of 209 participants aged 60-65. Blood plasma glucose was measured from venous blood samples. Individual Prudent and Western dietary patterns were estimated from a self-completed food frequency questionnaire. The relationship between dietary patterns, diabetes, and blood glucose was assessed via general linear model analyses controlling for age, sex, height, and total caloric intake. Results indicated that there was no association between Prudent diet and fasting blood glucose levels, or type 2 diabetes. In contrast, an individual in the upper tertile for Western dietary score had a significantly higher risk of having diabetes than an individual in the lower tertile for Western dietary score. However, there was no significant association between Western diet and fasting blood glucose. Western diet may be associated with type 2 diabetes through mechanisms beyond impacting blood plasma glucose directly. The fact that the association between Western diet and type 2 diabetes remained even when total caloric intake was controlled for highlights the need for policy and population health interventions targeting the reduction of unhealthy food consumption.

  16. Adiposity indicators lipid accumulation product and triglyceride-glucose index as alternate criteria for the diagnosis of metabolic obesity in adult

    OpenAIRE

    Mariya Tabassum; Md. Matiur Rahman; Miliva Mozaffor

    2018-01-01

    Metabolic obesity refers to the state of having metabolic syndrome irrespective of one’s BMI. This study was aimed to elucidate the lipid accumulation product and triglyceride-glucose index as simple and alternate criteria for the detecting metabolic obesity in adult. The study was conducted in 200 adult (age range: 19-45 years). According to lipid accumulation product and Triglyceride-glucose index, the prevalence of metabolic obesity was 54.0% and 53.5% respectively. With a cutoff value of ...

  17. Adult-onset obesity reveals prenatal programming of glucose-insulin sensitivity in male sheep nutrient restricted during late gestation.

    Directory of Open Access Journals (Sweden)

    Philip Rhodes

    Full Text Available BACKGROUND: Obesity invokes a range of metabolic disturbances, but the transition from a poor to excessive nutritional environment may exacerbate adult metabolic dysfunction. The current study investigated global maternal nutrient restriction during early or late gestation on glucose tolerance and insulin sensitivity in the adult offspring when lean and obese. METHODS/PRINCIPAL FINDINGS: Pregnant sheep received adequate (1.0M; CE, n = 6 or energy restricted (0.7M diet during early (1-65 days; LEE, n = 6 or late (65-128 days; LEL, n = 7 gestation (term approximately 147 days. Subsequent offspring remained on pasture until 1.5 years when all received glucose and insulin tolerance tests (GTT & ITT and body composition determination by dual energy x-ray absorptiometry (DXA. All animals were then exposed to an obesogenic environment for 6-7 months and all protocols repeated. Prenatal dietary treatment had no effect on birth weight or on metabolic endpoints when animals were 'lean' (1.5 years. Obesity revealed generalised metabolic 'inflexibility' and insulin resistance; characterised by blunted excursions of plasma NEFA and increased insulin(AUC (from 133 to 341 [s.e.d. 26] ng.ml(-1.120 mins during a GTT, respectively. For LEL vs. CE, the peak in plasma insulin when obese was greater (7.8 vs. 4.7 [s.e.d. 1.1] ng.ml(-1 and was exacerbated by offspring sex (i.e. 9.8 vs. 4.4 [s.e.d. 1.16] ng.ml(-1; LEL male vs. CE male, respectively. Acquisition of obesity also significantly influenced the plasma lipid and protein profile to suggest, overall, greater net lipogenesis and reduced protein metabolism. CONCLUSIONS: This study indicates generalised metabolic dysfunction with adult-onset obesity which also exacerbates and 'reveals' programming of glucose-insulin sensitivity in male offspring prenatally exposed to maternal undernutrition during late gestation. Taken together, the data suggest that metabolic function appears little compromised in young

  18. Metformin modifies the exercise training effects on risk factors for cardiovascular disease in impaired glucose tolerant adults

    Science.gov (United States)

    Malin, Steven K.; Nightingale, Joy; Choi, Sung-Eun; Chipkin, Stuart R.; Braun, Barry

    2012-01-01

    Impaired glucose tolerant (IGT) adults are at elevated risk for cardiovascular disease (CVD). Exercise or metformin reduce CVD risk, but the efficacy of combining treatments is unclear. To determine the effects of exercise training plus metformin, compared to each treatment alone, on CVD risk factors in IGT adults. Subjects were assigned to: placebo (P), metformin (M), exercise plus placebo (EP), or exercise plus metformin (EM) (8/group). In a double-blind design, P or 2000mg/d of M were administered for 12 weeks and half performed aerobic and resistance training 3 days/week for approximately 60 minutes/day at 70% pre-training heart rate peak. Outcomes included: adiposity, blood pressure (BP), lipids and high sensitivity C-reactive protein (hs-CRP). Z-scores were calculated to determine metabolic syndrome severity. M and EM, but not EP, decreased body weight compared to P (p metabolic syndrome Z-score compared to baseline (EP; trend p = 0.07 and EM or M; p exercise and/or metformin improve some CVD risk factors, only training or metformin alone lowered hs-CRP and BP. Thus, metformin may attenuate the effects of training on some CVD risk factors and metabolic syndrome severity in IGT adults. PMID:23505172

  19. Diabetes Technology-Continuous Subcutaneous Insulin Infusion Therapy and Continuous Glucose Monitoring in Adults: An Endocrine Society Clinical Practice Guideline.

    Science.gov (United States)

    Peters, Anne L; Ahmann, Andrew J; Battelino, Tadej; Evert, Alison; Hirsch, Irl B; Murad, M Hassan; Winter, William E; Wolpert, Howard

    2016-11-01

    To formulate clinical practice guidelines for the use of continuous glucose monitoring and continuous subcutaneous insulin infusion in adults with diabetes. The participants include an Endocrine Society-appointed Task Force of seve