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Sample records for change insulin sensitivity

  1. Insulin sensitizers prevent fine particulate matter-induced vascular insulin resistance and changes in endothelial progenitor cell homeostasis.

    Science.gov (United States)

    Haberzettl, Petra; McCracken, James P; Bhatnagar, Aruni; Conklin, Daniel J

    2016-06-01

    Exposure to fine particular matter (PM2.5) increases the risk of developing cardiovascular disease and Type 2 diabetes. Because blood vessels are sensitive targets of air pollutant exposure, we examined the effects of concentrated ambient PM2.5 (CAP) on vascular insulin sensitivity and circulating levels of endothelial progenitor cells (EPCs), which reflect cardiovascular health. We found that CAP exposure for 9 days decreased insulin-stimulated Akt phosphorylation in the aorta of mice maintained on control diet. This change was accompanied by the induction of IL-1β and increases in the abundance of cleaved IL-18 and p10 subunit of Casp-1, consistent with the activation of the inflammasome pathway. CAP exposure also suppressed circulating levels of EPCs (Flk-1(+)/Sca-1(+) cells), while enhancing the bone marrow abundance of these cells. Although similar changes in vascular insulin signaling and EPC levels were observed in mice fed high-fat diet, CAP exposure did not exacerbate diet-induced changes in vascular insulin resistance or EPC homeostasis. Treatment with an insulin sensitizer, metformin or rosiglitazone, prevented CAP-induced vascular insulin resistance and NF-κB and inflammasome activation and restored peripheral blood and bone marrow EPC levels. These findings suggest that PM2.5 exposure induces diet-independent vascular insulin resistance and inflammation and prevents EPC mobilization, and that this EPC mobilization defect could be mediated by vascular insulin resistance. Impaired vascular insulin sensitivity may be an important mechanism underlying PM2.5-induced vascular injury, and pharmacological sensitization to insulin action could potentially prevent deficits in vascular repair and mitigate vascular inflammation due to exposure to elevated levels of ambient air pollution. PMID:27016579

  2. Does bicarbonated mineral water rich in sodium change insulin sensitivity of postmenopausal women?

    Directory of Open Access Journals (Sweden)

    S. Schoppen

    2007-10-01

    Full Text Available Aim: To study the effects of drinking 0.5 L of two sodium-rich bicarbonated mineral waters (BMW-1 and 2, with a standard meal, on postprandial insulin and glucose changes. And to determine, if the effects vary depending on insulin resistance, measured by homeostasis model assessment (HOMA. Methods: In a 3-way randomized crossover study, 18 healthy postmenopausal women consumed two sodiumrich BMWs and a low-mineral water (LMW with a standard fat-rich meal. Fasting and postprandial blood samples were taken at 30, 60 and 120 min. Serum glucose, insulin, cholesterol and triacylglycerols were determined. Insulin resistance was estimated by HOMA and insulin sensitivity was calculated by quantitative insulin sensitivity check index (QUICKY. Results: Glucose levels did not change. HOMA and QUICKY values were highly inversely correlated (r = -1,000; p < 0.0001. Insulin concentrations showed a significant time effect (p < 0.0001 and a significant water x time interaction (p < 0.021. At 120 min insulin levels with BMW-1 were significantly lower than with LMW (p = 0.022. Postprandial insulin concentrations showed significantly different patterns of mineral water intake depending on HOMA n-tiles (p = 0.016. Conclusion: Results suggests an increase in insulin sensitivity after BMWs consumption. This effect is more marked in the women, who have higher HOMA values. These waters should be considered part of a healthy diet in order to prevent insulin resistance and cardiovascular disease.

  3. Metabolic and fibrinolytic response to changed insulin sensitivity in users of oral contraceptives

    DEFF Research Database (Denmark)

    Petersen, Kresten R.; Christiansen, Erik; Madsbad, Sten;

    1999-01-01

    systems, are relevant in the evaluation of the risk of developing vascular disorders or diabetes in OC users. We studied insulin sensitivity index (S(I)), glucose effectiveness (S(g)), and insulin response in young, healthy women by frequently sampled intravenous glucose tolerance tests before and after......The fundamental role of insulin resistance for metabolic changes linked to cardiovascular disease and type 2 diabetes is increasingly recognized. Oral contraceptives (OC) may affect insulin sensitivity, and a detailed characterization hereof, as well as the secondary effects on related metabolic...

  4. Endocrine determinants of changes in insulin sensitivity and insulin secretion during a weight cycle in healthy men.

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    Judith Karschin

    Full Text Available Changes in insulin sensitivity (IS and insulin secretion occur with perturbations in energy balance and glycemic load (GL of the diet that may precede the development of insulin resistance and hyperinsulinemia. Determinants of changes in IS and insulin secretion with weight cycling in non-obese healthy subjects remain unclear.In a 6wk controlled 2-stage randomized dietary intervention 32 healthy men (26±4y, BMI: 24±2kg/m2 followed 1wk of overfeeding (OF, 3wks of caloric restriction (CR containing either 50% or 65% carbohydrate (CHO and 2wks of refeeding (RF with the same amount of CHO but either low or high glycaemic index at ±50% energy requirement. Measures of IS (basal: HOMA-index, postprandial: Matsuda-ISI, insulin secretion (early: Stumvoll-index, total: tAUC-insulin/tAUC-glucose and potential endocrine determinants (ghrelin, leptin, adiponectin, thyroid hormone levels, 24h-urinary catecholamine excretion were assessed.IS improved and insulin secretion decreased due to CR and normalized upon RF. Weight loss-induced improvements in basal and postprandial IS were associated with decreases in leptin and increases in ghrelin levels, respectively (r = 0.36 and r = 0.62, p<0.05. Weight regain-induced decrease in postprandial IS correlated with increases in adiponectin, fT3, TSH, GL of the diet and a decrease in ghrelin levels (r-values between -0.40 and 0.83, p<0.05 whereas increases in early and total insulin secretion were associated with a decrease in leptin/adiponectin-ratio (r = -0.52 and r = -0.46, p<0.05 and a decrease in fT4 (r = -0.38, p<0.05 for total insulin secretion only. After controlling for GL associations between RF-induced decrease in postprandial IS and increases in fT3 and TSH levels were no longer significant.Weight cycling induced changes in IS and insulin secretion were associated with changes in all measured hormones, except for catecholamine excretion. While leptin, adiponectin and ghrelin seem to be the major

  5. Insulin sensitivity and albuminuria

    DEFF Research Database (Denmark)

    Pilz, Stefan; Rutters, Femke; Nijpels, Giel;

    2014-01-01

    OBJECTIVE: Accumulating evidence suggests an association between insulin sensitivity and albuminuria, which, even in the normal range, is a risk factor for cardiovascular diseases. We evaluated whether insulin sensitivity is associated with albuminuria in healthy subjects. RESEARCH DESIGN...... AND METHODS: We investigated 1,415 healthy, nondiabetic participants (mean age 43.9 ± 8.3 years; 54.3% women) from the RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study, of whom 852 participated in a follow-up examination after 3 years. At baseline, insulin sensitivity...... was assessed by hyperinsulinemic-euglycemic clamps, expressed as the M/I value. Oral glucose tolerance test-based insulin sensitivity (OGIS), homeostasis model assessment of insulin resistance (HOMA-IR), and urinary albumin-to-creatinine ratio (UACR) were determined at baseline and follow-up. RESULTS...

  6. Determining pancreatic β-cell compensation for changing insulin sensitivity using an oral glucose tolerance test

    DEFF Research Database (Denmark)

    Solomon, Thomas; Malin, Steven K; Karstoft, Kristian;

    2014-01-01

    Plasma glucose, insulin, and C-peptide responses during an OGTT are informative for both research and clinical practice in type 2 diabetes. The aim of this study was to use such information to determine insulin sensitivity and insulin secretion so as to calculate an oral glucose disposition index...

  7. Relationship of Insulin Sensitivity, Insulin Secretion, and Adiposity With Insulin Clearance in a Multiethnic Population

    OpenAIRE

    Lorenzo, Carlos; Hanley, Anthony J.G.; Wagenknecht, Lynne E; Rewers, Marian J.; Stefanovski, Darko; Goodarzi, Mark O.; Haffner, Steven M

    2012-01-01

    OBJECTIVE We aimed to examine insulin clearance, a compensatory mechanism to changes in insulin sensitivity, across sex, race/ethnicity populations, and varying states of glucose tolerance. RESEARCH DESIGN AND METHODS We measured insulin sensitivity index (S I), acute insulin response (AIR), and metabolic clearance rate of insulin (MCRI) by the frequently sampled intravenous glucose tolerance test in 1,295 participants in the Insulin Resistance Atherosclerosis Study. RESULTS MCRI was positive...

  8. Macro fat and micro fat: insulin sensitivity and gender dependent response of adipose tissue to isocaloric diet change.

    Science.gov (United States)

    Li, Yanjun; Gaillard, Jonathan R; McLaughlin, Tracey; Sørensen, Thorkild Ia; Periwal, Vipul

    2015-01-01

    The adipose cell-size distribution is a quantitative characterization of adipose tissue morphology. At a population level, the adipose cell-size distribution is insulin-sensitivity dependent, and the observed correlation between obesity and insulin resistance is believed to play a key role in the metabolic syndrome. Changes in fat mass can be induced by altered energy intake or even diet composition. These macroscopic changes must manifest themselves as dynamic adipose cell-size distribution alterations at the microscopic level. The dynamic relationship between these 2 independent measurements of body fat is unknown. In this study, we investigate adipose tissue dynamics in response to various isocaloric diet compositions, comparing gender- and insulin sensitivity-dependent differences. A body composition model is used to predict fat mass changes in response to changes in diet composition for 28 individuals, separated into 4 subgroups according to gender and insulin sensitivity/resistance. Adipose cell-size distribution changes in each individual are simulated with a dynamic model and parameters corresponding to lipid turnover and cell growth rates are determined for each subgroup to match the relative change of fat mass for each diet composition, respectively. We find that adipose cell-size dynamics are associated with different modulations dependent on gender and insulin resistance. Larger turnover and growth/shrinkage rates in insulin resistant individuals suggest they may be more sensitive to changes in energy intake and diet composition than insulin sensitive subjects. The different cell-size distribution changes of adipose cells of various sizes in different subject groups further suggest distinct modulations of adipose cell dynamics. PMID:26451281

  9. Macro fat and micro fat: insulin sensitivity and gender dependent response of adipose tissue to isocaloric diet change.

    Science.gov (United States)

    Li, Yanjun; Gaillard, Jonathan R; McLaughlin, Tracey; Sørensen, Thorkild Ia; Periwal, Vipul

    2015-01-01

    The adipose cell-size distribution is a quantitative characterization of adipose tissue morphology. At a population level, the adipose cell-size distribution is insulin-sensitivity dependent, and the observed correlation between obesity and insulin resistance is believed to play a key role in the metabolic syndrome. Changes in fat mass can be induced by altered energy intake or even diet composition. These macroscopic changes must manifest themselves as dynamic adipose cell-size distribution alterations at the microscopic level. The dynamic relationship between these 2 independent measurements of body fat is unknown. In this study, we investigate adipose tissue dynamics in response to various isocaloric diet compositions, comparing gender- and insulin sensitivity-dependent differences. A body composition model is used to predict fat mass changes in response to changes in diet composition for 28 individuals, separated into 4 subgroups according to gender and insulin sensitivity/resistance. Adipose cell-size distribution changes in each individual are simulated with a dynamic model and parameters corresponding to lipid turnover and cell growth rates are determined for each subgroup to match the relative change of fat mass for each diet composition, respectively. We find that adipose cell-size dynamics are associated with different modulations dependent on gender and insulin resistance. Larger turnover and growth/shrinkage rates in insulin resistant individuals suggest they may be more sensitive to changes in energy intake and diet composition than insulin sensitive subjects. The different cell-size distribution changes of adipose cells of various sizes in different subject groups further suggest distinct modulations of adipose cell dynamics.

  10. Euglycemic clamp insulin sensitivity and longitudinal systolic blood pressure

    DEFF Research Database (Denmark)

    Petrie, John R; Malik, Muhammad Omar; Balkau, Beverley;

    2013-01-01

    Insulin resistance may be an independent risk factor for the development of hypertension, but change in blood pressure (BP) over time has not been adequately studied in healthy individuals fully characterized for insulin sensitivity. In the Relationship between Insulin Sensitivity...

  11. Cinnamon, glucose and insulin sensitivity

    Science.gov (United States)

    Compounds found in cinnamon not only improve the function of insulin but also function as antioxidants and may be anti-inflammatory. This is very important since insulin function, antioxidant status, and inflammatory response are closely linked; with decreased insulin sensitivity there is also decr...

  12. Changes in androgens and insulin sensitivity indexes throughout pregnancy in women with polycystic ovary syndrome (PCOS): relationships with adverse outcomes

    OpenAIRE

    Falbo Angela; Rocca Morena; Russo Tiziana; D'Ettore Antonietta; Tolino Achille; Zullo Fulvio; Orio Francesco; Palomba Stefano

    2010-01-01

    Abstract Background Given the high rate of pregnancy and perinatal complications recently observed in patients with polycystic ovary syndrome (PCOS) and the lack of data on the serum variations in androgens and insulin sensitivity indexes in pregnant women with PCOS, the current study was aimed to assess these changes and their potential effect on pregnancy outcomes in a population of women with PCOS. Methods Forty-five pregnant patients with ovulatory PCOS (PCOS group) and other 42 healthy p...

  13. Insulin Sensitivity of Heifers on Different Diets

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    Luthman J

    2002-06-01

    Full Text Available The hyperinsulinemic euglycemic clamp technique was used to investigate the effect on insulin sensitivity of 2 different diets used in practical cattle feeding in calves. Ten 4 to 5-month-old heifer calves were allocated to 2 feeding groups, LO or HI, to obtain growth rates of 400 g/day or 900 g/day. The heifers were fed and housed individually for 5 weeks. Growth rates close to calculated rates were obtained with the diets used. Weekly blood samples were collected from the jugular vein for analysis of glucose, insulin, cortisol, total serum protein, urea, cholesterol and nonesterified fatty acids. During week 5, insulin sensitivity was estimated using the hyperinsulinemic euglycemic clamp technique. Insulin sensitivity did not differ between the groups, but the plasma glucose levels were higher during weeks 3 and 4 for the HI group compared to the LO group. It may be concluded that the amount of concentrate in the diet was too low to induce changes in either the basal plasma insulin levels or the insulin sensitivity in the HI group.

  14. Quantification of adipose tissue insulin sensitivity

    DEFF Research Database (Denmark)

    Søndergaard, Esben; Jensen, Michael D

    2016-01-01

    In metabolically healthy humans, adipose tissue is exquisitely sensitive to insulin. Similar to muscle and liver, adipose tissue lipolysis is insulin resistant in adults with central obesity and type 2 diabetes. Perhaps uniquely, however, insulin resistance in adipose tissue may directly contribute...... to development of insulin resistance in muscle and liver because of the increased delivery of free fatty acids to those tissues. It has been hypothesized that insulin adipose tissue resistance may precede other metabolic defects in obesity and type 2 diabetes. Therefore, precise and reproducible...... quantification of adipose tissue insulin sensitivity, in vivo, in humans, is an important measure. Unfortunately, no consensus exists on how to determine adipose tissue insulin sensitivity. We review the methods available to quantitate adipose tissue insulin sensitivity and will discuss their strengths and...

  15. Quantification of adipose tissue insulin sensitivity.

    Science.gov (United States)

    Søndergaard, Esben; Jensen, Michael D

    2016-06-01

    In metabolically healthy humans, adipose tissue is exquisitely sensitive to insulin. Similar to muscle and liver, adipose tissue lipolysis is insulin resistant in adults with central obesity and type 2 diabetes. Perhaps uniquely, however, insulin resistance in adipose tissue may directly contribute to development of insulin resistance in muscle and liver because of the increased delivery of free fatty acids to those tissues. It has been hypothesized that insulin adipose tissue resistance may precede other metabolic defects in obesity and type 2 diabetes. Therefore, precise and reproducible quantification of adipose tissue insulin sensitivity, in vivo, in humans, is an important measure. Unfortunately, no consensus exists on how to determine adipose tissue insulin sensitivity. We review the methods available to quantitate adipose tissue insulin sensitivity and will discuss their strengths and weaknesses.

  16. Improvements in glucose tolerance and insulin sensitivity after lifestyle intervention are related to changes in serum fatty acid profile and desaturase activities: the SLIM study

    NARCIS (Netherlands)

    Corpeleijn, E.; Feskens, E.J.M.; Jansen, E.H.J.M.; Mensink, M.R.; Saris, W.H.M.; Bruin, de T.W.A.; Blaak, E.E.

    2006-01-01

    AIMS/HYPOTHESIS: The aim of this study was to investigate whether lifestyle intervention-induced changes in serum fatty acid profile of cholesteryl esters and estimated desaturase activities are related to improvements in insulin sensitivity in subjects at risk of type 2 diabetes. MATERIALS AND METH

  17. Longitudinal changes in insulin sensitivity and body composition of small-for-gestational-age adolescents after cessation of growth hormone treatment

    NARCIS (Netherlands)

    R.H. Willemsen (Ruben); A.C.S. Hokken-Koelega (Anita)

    2008-01-01

    textabstractContext: GH treatment reduces insulin sensitivity (Si). For small-for-gestational-age (SGA) subjects, who might have an increased risk to develop cardiovascular disease and type 2 diabetes, it is still uncertain how Si, β-cell function, and body composition change over time after stoppin

  18. Improvements in glucose tolerance and insulin sensitivity after lifestyle intervention are related to changes in serum fatty acid profile and desaturase activities : the SLIM study

    NARCIS (Netherlands)

    Corpeleijn, E.; Feskens, E. J. M.; Jansen, E. H. J. M.; Mensink, M.; Saris, W. H. M.; de Bruin, T. W. A.; Blaak, E. E.

    2006-01-01

    Aims/hypothesis: The aim of this study was to investigate whether lifestyle intervention-induced changes in serum fatty acid profile of cholesteryl esters and estimated desaturase activities are related to improvements in insulin sensitivity in subjects at risk of type 2 diabetes. Materials and meth

  19. Increased skeletal muscle capillarization enhances insulin sensitivity

    DEFF Research Database (Denmark)

    Åkerström, Thorbjörn; Laub, Lasse; Vedel, Kenneth;

    2014-01-01

    Increased skeletal muscle capillarization is associated with improved glucose tolerance and insulin sensitivity. However, a possible causal relationship has not previously been identified. We therefore investigated whether increased skeletal muscle capillarization increases insulin sensitivity......-body insulin sensitivity increased by ~24% and insulin-stimulated skeletal muscle 2-deoxy-[(3)H]-Glucose disposal increased by ~30% concomitant with a ~20% increase in skeletal muscle capillarization. Adipose tissue insulin sensitivity was not affected by the treatment. Insulin-stimulated muscle glucose uptake...... the rats on any other parameters measured. We conclude that an increase in skeletal muscle capillarization is associated with increased insulin sensitivity. These data point towards the importance of increasing skeletal muscle capillarization for prevention or treatment of type 2 diabetes....

  20. Insulin sensitivity : modulation by the brain

    NARCIS (Netherlands)

    Coomans, Claudia Pascalle

    2012-01-01

    The studies in this thesis contribute to the understanding of the role of the brain in insulin sensitivity. We demonstrate that disturbances in circadian rhythm resulting in alterations in SCN output, can contribute to the development of insulin resistance. We also shown that insulin-stimulated gluc

  1. Protein restriction in early life is associated with changes in insulin sensitivity and pancreatic β-cell function during pregnancy.

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    Ignácio-Souza, Letícia Martins; Reis, Sílvia Regina; Arantes, Vanessa Cristina; Botosso, Bárbara Laet; Veloso, Roberto Vilela; Ferreira, Fabiano; Boschero, Antonio Carlos; Carneiro, Everardo Magalhães; Reis, Marise Auxiliadora de Barros; Latorraca, Márcia Queiroz

    2013-01-28

    Malnutrition in early life impairs glucose-stimulated insulin secretion in adulthood. Conversely, pregnancy is associated with a significant increase in glucose-stimulated insulin secretion under conditions of normoglycaemia. A failure in β-cell adaptive changes may contribute to the onset of diabetes. Thus, glucose homeostasis and β-cell function were evaluated in control-fed pregnant (CP) and non-pregnant (CNP) or protein-restricted pregnant (LPP) and non-pregnant (LPNP) rats, from fetal to adult life, and in protein-restricted rats that were recovered after weaning (RP and RNP). The typical insulin resistance of pregnancy was not observed in the RP rats, nor did pregnancy increase the insulin content/islet in the LPP group. The glucose dose-response curves from pregnant rats were shifted to the left in relation to the non-pregnant rats, except in the recovered group. Glucose utilisation but not oxidation in islets from the RP and LPP groups was reduced at a concentration of 8.3 mm-glucose compared with islets from the CP group. Cyclic AMP content and the potentiation of glucose-stimulated insulin secretion by isobutylmethylxanthine at a concentration of 2.8 mm-glucose indicated increased adenylyl cyclase 3 activity but reduced protein kinase A-α activity in islets from the RP and LPP rats. Protein kinase C (PKC)-α but not phospholipase C (PLC)-β1 expression was reduced in islets from the RP group. Phorbol-12-myristate 13-acetate produced a less potent stimulation of glucose-stimulated insulin secretion in the RP group. Thus, the alterations exhibited by islets from the LPP group appeared to be due to reduced islet mass and/or insulin biosynthesis. In the RP group the loss of the adaptive capacity apparently resulted from uncoupling between glucose metabolism and the amplifying signals of the secretory process, as well as a severe attenuation of the PLC/PKC pathway. PMID:22475371

  2. Early Skeletal Muscle Adaptations to Short-Term High-Fat Diet in Humans Prior to Changes in Insulin Sensitivity

    OpenAIRE

    Anderson, Angela S.; Haynie, Kimberly R.; McMillan, Ryan P; Osterberg, Kristen L.; Boutagy, Nabil E.; Frisard, Madlyn I.; Davy, Brenda M.; Davy, Kevin P.; Hulver, Matthew W.

    2015-01-01

    Objective The purpose of this investigation was to understand the metabolic adaptations to a short-term (5 days), isocaloric, high fat diet (HFD) in healthy, young males. Methods Two studies were undertaken with 12 subjects. Study 1 investigated the effect of the HFD on skeletal muscle substrate metabolism and insulin sensitivity. Study 2 assessed the metabolic and transcriptional response in skeletal muscle to the transition from a fasted-to-fed state using a high fat meal challenge prior to...

  3. Pancreatic beta-cell function is a stronger predictor of changes in glycemic control after an aerobic exercise intervention than insulin sensitivity

    DEFF Research Database (Denmark)

    Solomon, Thomas; Malin, Steven K; Karstoft, Kristian;

    2013-01-01

    ContextUnderstanding inter-subject variability in glycemic control following exercise training will help individualize treatment.ObjectiveTo determine whether this variability is related to training-induced changes in insulin sensitivity or pancreatic beta-cell function.Design, Setting......, and ParticipantsAn observational clinical study of N=105 subjects with impaired glucose tolerance or type 2 diabetes.Interventions and Main Outcome MeasuresIndividual subject changes in fitness (VO2max), glycemia (HbA1c, fasting glucose, OGTT), insulin sensitivity (Si; hyperinsulinemic-euglycemic clamp), oral...... glucose, and 2-hour OGTT glucose, were reduced in 69%, 62%, and 68% of subjects respectively; while Si improved in 90% of the participants. Changes in glycemic control were congruent with changes in GSIS such that 66% of subjects had a reduction in first-phase GSIS, and 46% had reduced second-phase GSIS...

  4. Salt sensitivity correlates positively with insulin sensitivity in healthy volunteers

    NARCIS (Netherlands)

    ter Maaten, JC; Voordouw, JJ; Bakker, SJL; Gans, ROB

    1999-01-01

    Background The aim of the study was to assess the relationship between insulin sensitivity and salt sensitivity in healthy subjects who display a wide range of insulin sensitivity. As a secondary objective, we assessed the relationship between salt sensitivity and the other characteristics of the in

  5. Longitudinal changes in insulin sensitivity and body composition of small-for-gestational-age adolescents after cessation of growth hormone treatment

    OpenAIRE

    Willemsen, Ruben; Hokken-Koelega, Anita

    2008-01-01

    textabstractContext: GH treatment reduces insulin sensitivity (Si). For small-for-gestational-age (SGA) subjects, who might have an increased risk to develop cardiovascular disease and type 2 diabetes, it is still uncertain how Si, β-cell function, and body composition change over time after stopping GH treatment. Objective: Our objective was to investigate longitudinal changes in Si, β-cell function, and body composition after cessation of long-term GH treatment. Design and Patients: We cond...

  6. Role of PKCδ in Insulin Sensitivity and Skeletal Muscle Metabolism

    DEFF Research Database (Denmark)

    Li, Mengyao; Vienberg, Sara G; Bezy, Olivier;

    2015-01-01

    Protein kinase C (PKC)δ has been shown to be increased in liver in obesity and plays an important role in the development of hepatic insulin resistance in both mice and humans. In the current study, we explored the role of PKCδ in skeletal muscle in the control of insulin sensitivity and glucose......-body insulin sensitivity and muscle insulin resistance and by 15 months of age improved the age-related decline in whole-body glucose tolerance. At 15 months of age, M-PKCδKO mice also exhibited decreased metabolic rate and lower levels of some proteins of the OXPHOS complex suggesting a role for PKCδ in the...... metabolism by generating mice in which PKCδ was deleted specifically in muscle using Cre-lox recombination. Deletion of PKCδ in muscle improved insulin signaling in young mice, especially at low insulin doses; however, this did not change glucose tolerance or insulin tolerance tests done with pharmacological...

  7. Di-(2-ethylhexyl phthalate metabolites in urine show age-related changes and associations with adiposity and parameters of insulin sensitivity in childhood.

    Directory of Open Access Journals (Sweden)

    Arianna Smerieri

    Full Text Available Phthalates might be implicated with obesity and insulin sensitivity. We evaluated the levels of primary and secondary metabolites of Di-(2-ethylhexyl phthalate (DEHP in urine in obese and normal-weight subjects both before and during puberty, and investigated their relationships with auxological parameters and indexes of insulin sensitivity.DEHP metabolites (MEHP, 6-OH-MEHP, 5-oxo-MEHP, 5-OH-MEHP, and 5-CX-MEHP, were measured in urine by RP-HPLC-ESI-MS. Traditional statistical analysis and a data mining analysis using the Auto-CM analysis were able to offer an insight into the complex biological connections between the studied variables.The data showed changes in DEHP metabolites in urine related with obesity, puberty, and presence of insulin resistance. Changes in urine metabolites were related with age, height and weight, waist circumference and waist to height ratio, thus to fat distribution. In addition, clear relationships in both obese and normal-weight subjects were detected among MEHP, its products of oxidation and measurements of insulin sensitivity.It remains to be elucidated whether exposure to phthalates per se is actually the risk factor or if the ability of the body to metabolize phthalates is actually the key point. Further studies that span from conception to elderly subjects besides further understanding of DEHP metabolism are warranted to clarify these aspects.

  8. Increased skeletal muscle capillarization enhances insulin sensitivity.

    Science.gov (United States)

    Akerstrom, Thorbjorn; Laub, Lasse; Vedel, Kenneth; Brand, Christian Lehn; Pedersen, Bente Klarlund; Lindqvist, Anna Kaufmann; Wojtaszewski, Jørgen F P; Hellsten, Ylva

    2014-12-15

    Increased skeletal muscle capillarization is associated with improved glucose tolerance and insulin sensitivity. However, a possible causal relationship has not previously been identified. Therefore, we investigated whether increased skeletal muscle capillarization increases insulin sensitivity. Skeletal muscle-specific angiogenesis was induced by adding the α1-adrenergic receptor antagonist prazosin to the drinking water of Sprague-Dawley rats (n = 33), whereas 34 rats served as controls. Insulin sensitivity was measured ≥40 h after termination of the 3-wk prazosin treatment, which ensured that prazosin was cleared from the blood stream. Whole body insulin sensitivity was measured in conscious, unrestrained rats by hyperinsulinemic euglycemic clamp. Tissue-specific insulin sensitivity was assessed by administration of 2-deoxy-[(3)H]glucose during the plateau phase of the clamp. Whole body insulin sensitivity increased by ∼24%, and insulin-stimulated skeletal muscle 2-deoxy-[(3)H]glucose disposal increased by ∼30% concomitant with an ∼20% increase in skeletal muscle capillarization. Adipose tissue insulin sensitivity was not affected by the treatment. Insulin-stimulated muscle glucose uptake was enhanced independent of improvements in skeletal muscle insulin signaling to glucose uptake and glycogen synthesis, suggesting that the improvement in insulin-stimulated muscle glucose uptake could be due to improved diffusion conditions for glucose in the muscle. The prazosin treatment did not affect the rats on any other parameters measured. We conclude that an increase in skeletal muscle capillarization is associated with increased insulin sensitivity. These data point toward the importance of increasing skeletal muscle capillarization for prevention or treatment of type 2 diabetes. PMID:25352432

  9. Insulin resistance, insulin sensitization and inflammation in polycystic ovarian syndrome

    Directory of Open Access Journals (Sweden)

    Dhindsa G

    2004-04-01

    Full Text Available It is estimated that 5-10% of women of reproductive age have polycystic ovarian syndrome (PCOS. While insulin resistance is not part of the diagnostic criteria for PCOS, its importance in the pathogenesis of PCOS cannot be denied. PCOS is associated with insulin resistance independent of total or fat-free body mass. Post-receptor defects in the action of insulin have been described in PCOS which are similar to those found in obesity and type 2 diabetes. Treatment with insulin sensitizers, metformin and thiazolidinediones, improve both metabolic and hormonal patterns and also improve ovulation in PCOS. Recent studies have shown that PCOS women have higher circulating levels of inflammatory mediators like C-reactive protein, tumour necrosis factor- , tissue plasminogen activator and plasminogen activator inhibitor-1 (PAI-1 . It is possible that the beneficial effect of insulin sensitizers in PCOS may be partly due to a decrease in inflammation.

  10. Diclofenac derivatives with insulin-sensitizing activity

    Institute of Scientific and Technical Information of China (English)

    Jian Ta Wang; Ying Wang; Ji Quan Zhang; Xing Cui; Yi Zhang; Gao Feng Zhu; Lei Tang

    2011-01-01

    A series of diclofenac derivatives were synthesized. The insulin-sensitizing activity of 28 new compounds was evaluated in 3T3-L1 cells. The compounds 10a and 10f exhibited similar insulin-sensitizing activity with positive drag rosiglitazone.

  11. Insulin sensitivity and hemodynamic responses to insulin in Wistar-Kyoto and spontaneously hypertensive rats.

    Science.gov (United States)

    Pître, M; Nadeau, A; Bachelard, H

    1996-10-01

    The insulin-mediated vasodilator effect has been proposed as an important physiological determinant of insulin action on glucose disposal in normotensive humans. The present study was designed to further examine the acute regional hemodynamic effects of insulin in different vascular beds and to explore the relationships between insulin vascular effects and insulin sensitivity during euglycemic hyperinsulinemic clamps in conscious normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The rats were instrumented with intravascular catheters and pulsed Doppler flow probes to measure blood pressure, heart rate, and regional blood flows. In WKY rats, the euglycemic infusion of insulin (4 and 16 mU.kg-1.min-1) causes vasodilations in renal and hindquarter vascular beds but no changes in mean blood pressure, heart rate, or superior mesenteric vascular conductance. In contrast, in SHR, the same doses of insulin produce vasoconstrictions in superior mesenteric and hindquarter vascular beds and, at high doses, increase blood pressure. Moreover, at the lower dose of insulin tested, we found a reduction in the insulin sensitivity index in the SHR compared with the WKY rats. The present findings provide further evidence for an association between insulin sensitivity and insulin-mediated hemodynamic responses.

  12. Changes in glucose tolerance and insulin sensitivity following 2 weeks of daily cinnamon ingestion in healthy humans

    DEFF Research Database (Denmark)

    Solomon, Thomas; Blannin, Andrew K

    2009-01-01

    Cinnamon can improve fasting glucose in humans yet data on insulin sensitivity are limited and controversial. Eight male volunteers (aged 25 +/- 1 years, body mass 76.5 +/- 3.0 kg, BMI 24.0 +/- 0.7 kg m(-2); mean +/- SEM) underwent two 14-day interventions involving cinnamon or placebo...... supplementation (3 g day(-1)). Placebo supplementation was continued for 5 days following this 14 day period. Oral glucose tolerance tests (OGTT) were performed on days 0, 1, 14, 16, 18, and 20. Cinnamon ingestion reduced the glucose response to OGTT on day 1 (-13.1 +/- 6.3% vs. day 0; P <0.05) and day 14 (-5...

  13. Insulin sensitivity in post-obese women

    DEFF Research Database (Denmark)

    Toubro, S; Western, P; Bülow, J;

    1994-01-01

    1. Both increased and decreased sensitivity to insulin has been proposed to precede the development of obesity. Therefore, insulin sensitivity was measured during a 2 h hyperinsulinaemia (100 m-units min-1 m-2) euglycaemic (4.5 mmol/l) glucose clamp combined with indirect calorimetry in nine weight......-1 kg-1, not significant). Basal plasma concentrations of free fatty acids were similar, but at the end of the clamp free fatty acids were lower in the post-obese women than in the control women (139 +/- 19 and 276 +/- 48 mumol/l, P = 0.02). 3. We conclude that the insulin sensitivity of glucose...... metabolism is unaltered in the post-obese state. The study, however, points to an increased antilipolytic insulin action in post-obese subjects, which may favour fat storage and lower lipid oxidation rate postprandially.(ABSTRACT TRUNCATED AT 250 WORDS)...

  14. Changes in insulin sensitivity precede changes in body composition during 14 days of step reduction combined with overfeeding in healthy young men

    DEFF Research Database (Denmark)

    Knudsen, Sine Haugaard; Hansen, Louise Seier; Pedersen, Maria;

    2012-01-01

    A lifestyle characterized by inactivity and a high-calorie diet is a known risk factor for impaired insulin sensitivity and development of Type 2 diabetes mellitus. To investigate possible links, nine young healthy men (24 ± 3 yr; body mass index of 21.6 ± 2.5 kg/m(2)) completed 14 days of step...... reduction (10,000 to 1,500 steps/day) and overfeeding (+50% kcal). Body composition (dual X-ray absorptiometry, MRI), aerobic fitness (maximal O(2) consumption), systemic inflammation and insulin sensitivity [oral glucose tolerance test (OGTT), hyperinsulinemic euglycemic clamp] were assessed before (day 0......), during (days 3 and 7), and immediately after the intervention (day 14), with follow-up tests (day 30). Body weight had increased at days 7 and 14 (P 7 and 14 (P...

  15. How can we measure insulin sensitivity?

    International Nuclear Information System (INIS)

    Insulin resistance is common in general population and prevalent in patients with obesity and Type 2 diabetes. Insulin sensitivity, reciprocal to insulin resistance, can be measured with a variety of experimental methods ranging from the 'gold' standard glucose clamp to the simple HOMA assessment. Each method has its merit and is applicable under different circumstances. Adoption of glucose tracers in the experimental protocols and more specifically in glucose clamp and minimal model allows hepatic vs. peripheral insulin sensitivity to be discriminated and estimated separately. The objective of this review is to give an account of the minimal modelling approach and provide summary information about other measurement methods together with information about reproducibility of the most popular methods, the minimal model and the glucose clamp techniques. (author)

  16. Exercise, pregnancy, and insulin sensitivity--what is new?

    DEFF Research Database (Denmark)

    Damm, Peter; Breitowicz, Bettina; Hegaard, Hanne Kristine

    2007-01-01

    Pregnancy is characterized by a marked physiological insulin resistance. Overweight and obesity or lack of physical activity can aggravate this reduced insulin sensitivity further. Increased insulin resistance has been associated with serious pregnancy complications, such as gestational diabetes...

  17. Calcineurin inhibitors acutely improve insulin sensitivity without affecting insulin secretion in healthy human volunteers

    DEFF Research Database (Denmark)

    Øzbay, Aygen; Møller, Niels; Juhl, Claus;

    2012-01-01

    of calcineurin inhibitors (CNIs) ciclosporin (CsA) and tacrolimus (Tac) has improved the outcome of organ transplants, but complications such as new onset diabetes mellitus after transplantation (NODAT) cause impairment of survival rates. The relative contribution of each CNI to the pathogenesis and development.......047), whereas first phase and pulsatile insulin secretion were unaffected. Coinciding with the CNI induced improved insulin sensitivity, glucose oxidation rates increased, while insulin clearance rates decreased, only non-significantly. Tac singularly lowered hsCRP concentrations, otherwise no changes were...

  18. Spectroscopic study of the interaction of insulin and its aptamer – sensitive optical detection of insulin

    International Nuclear Information System (INIS)

    The binding of insulin to the insulin binding aptamer (IBA) was investigated with different spectroscopy techniques (UV/vis absorption, fluorescence, resonance light-scattering spectra (RLS), synchronous fluorescence, and three-dimensional fluorescence). The thermodynamic parameters (Kb, ΔH, ΔG, and ΔS) of the insulin–IBA complex were further investigated by temperature-dependent fluorescence measurement over the range of 25–37 °C. The results of synchronous fluorescence, resonance light scattering (RLS) and three-dimensional fluorescence spectra showed that IBA would alter the structure of insulin. Folding of the dual-labeled insulin binding aptamer, FL-IBA, carrying 6-carboxyfluorescein (FAM) and 6-carboxytetramethylrhodamine (TAMRA) labels at termini of the insulin binding aptamer (IBA), into G-quadruplex leading to the contact quenching occurs as a result of the formation of a nonfluorescent complex between donor and acceptor. Significant fluorescent signal change when FL-IBA was bound to insulin is attributed to a conformational change in FL-IBA from a loose random coil to a compact G-quadruplex. Based on fluorescence quenching of IBA folding, a simple and sensitive insulin aptamer-based biosensor in the range of 2–70 nM was proposed. - Highlights: • The binding parameters were gotten from contact quenching data. • The binding of IBA induced some microenvironment and conformational changes in insulin. • The van der Waals interactions or hydrogen bonds play a major role on this binding. • A simple and sensitive insulin aptamer-based biosensor was proposed

  19. Spectroscopic study of the interaction of insulin and its aptamer – sensitive optical detection of insulin

    Energy Technology Data Exchange (ETDEWEB)

    Verdian-Doghaei, A.; Housaindokht, M.R., E-mail: housain@um.ac.ir

    2015-03-15

    The binding of insulin to the insulin binding aptamer (IBA) was investigated with different spectroscopy techniques (UV/vis absorption, fluorescence, resonance light-scattering spectra (RLS), synchronous fluorescence, and three-dimensional fluorescence). The thermodynamic parameters (K{sub b}, ΔH, ΔG, and ΔS) of the insulin–IBA complex were further investigated by temperature-dependent fluorescence measurement over the range of 25–37 °C. The results of synchronous fluorescence, resonance light scattering (RLS) and three-dimensional fluorescence spectra showed that IBA would alter the structure of insulin. Folding of the dual-labeled insulin binding aptamer, FL-IBA, carrying 6-carboxyfluorescein (FAM) and 6-carboxytetramethylrhodamine (TAMRA) labels at termini of the insulin binding aptamer (IBA), into G-quadruplex leading to the contact quenching occurs as a result of the formation of a nonfluorescent complex between donor and acceptor. Significant fluorescent signal change when FL-IBA was bound to insulin is attributed to a conformational change in FL-IBA from a loose random coil to a compact G-quadruplex. Based on fluorescence quenching of IBA folding, a simple and sensitive insulin aptamer-based biosensor in the range of 2–70 nM was proposed. - Highlights: • The binding parameters were gotten from contact quenching data. • The binding of IBA induced some microenvironment and conformational changes in insulin. • The van der Waals interactions or hydrogen bonds play a major role on this binding. • A simple and sensitive insulin aptamer-based biosensor was proposed.

  20. Chromium and Polyphenols from Cinnamon and Insulin Sensitivity

    Science.gov (United States)

    Factors that improve insulin sensitivity usually lead to improvements in risk factors associated with the metabolic syndrome, diabetes, and cardiovascular diseases. Naturally occurring bioactive compounds that have been shown to improve insulin sensitivity include chromium and polyphenols found in ...

  1. The impact of calcineurin inhibitors on insulin sensitivity and insulin secretion

    DEFF Research Database (Denmark)

    Øzbay, Aygen; Møller, N; Juhl, C;

    2012-01-01

    pulsatile insulin secretion were not significantly affected by the drugs. CONCLUSION: In conclusion, 8-10 days of treatment with cyclosporine and tacrolimus impairs insulin sensitivity to a similar degree in haemodialysis patients, while acute insulin responses and pulsatile insulin secretion remain...

  2. Improved insulin sensitivity after exercise: focus on insulin signaling

    DEFF Research Database (Denmark)

    Frøsig, Christian; Richter, Erik

    2009-01-01

    After a single bout of exercise, the ability of insulin to stimulate glucose uptake is markedly improved locally in the previously active muscles. This makes exercise a potent stimulus counteracting insulin resistance characterizing type 2 diabetes (T2D). It is believed that at least part...... of the mechanism relates to an improved ability of insulin to stimulate translocation of glucose transporters (GLUT4) to the muscle membrane after exercise. How this is accomplished is still unclear; however, an obvious possibility is that exercise interacts with the insulin signaling pathway to GLUT4...... translocation allowing for a more potent insulin response. Parallel to unraveling of the insulin signaling cascade, this has been investigated within the past 25 years. Reviewing existing studies clearly indicates that improved insulin action can occur independent of interactions with proximal insulin signaling...

  3. Insulin secretion and sensitivity in space flight: diabetogenic effects

    Science.gov (United States)

    Tobin, Brian W.; Uchakin, Peter N.; Leeper-Woodford, Sandra K.

    2002-01-01

    Nearly three decades of space flight research have suggested that there are subclinical diabetogenic changes that occur in microgravity. Alterations in insulin secretion, insulin sensitivity, glucose tolerance, and metabolism of protein and amino acids support the hypothesis that insulin plays an essential role in the maintenance of muscle mass in extended-duration space flight. Experiments in flight and after flight and ground-based bedrest studies have associated microgravity and its experimental paradigms with manifestations similar to those of diabetes, physical inactivity, and aging. We propose that these manifestations are characterized best by an etiology that falls into the clinical category of "other" causes of diabetes, including, but not restricted to, genetic beta-cell defects, insulin action defects, diseases of the endocrine pancreas, endocrinopathies, drug or chemically induced diabetes, infections, immune-mediated metabolic alteration, and a host of genetic related diseases. We present data showing alterations in tumor necrosis factor-alpha production, insulin secretion, and amino acid metabolism in pancreatic islets of Langerhans cultured in a ground-based cell culture bioreactor that mimics some of the effects of microgravity. Taken together, space flight research, ground-based studies, and bioreactor studies of pancreatic islets of Langerhans support the hypothesis that the pancreas is unable to overcome peripheral insulin resistance and amino acid dysregulation during space flight. We propose that measures of insulin secretion and insulin action will be necessary to design effective countermeasures against muscle loss, and we advance the "disposition index" as an essential model to be used in the clinical management of space flight-induced muscle loss.

  4. Greater omentectomy improves insulin sensitivity in nonobese dogs.

    Science.gov (United States)

    Lottati, Maya; Kolka, Cathryn M; Stefanovski, Darko; Kirkman, Erlinda L; Bergman, Richard N

    2009-04-01

    Visceral adiposity is strongly associated with insulin resistance; however, little evidence directly demonstrates that visceral fat per se impairs insulin action. Here, we examine the effects of the surgical removal of the greater omentum and its occupying visceral fat, an omentectomy (OM), on insulin sensitivity (S(I)) and beta-cell function in nonobese dogs. Thirteen male mongrel dogs were used in this research study; animals were randomly assigned to surgical treatment with either OM (n = 7), or sham-surgery (SHAM) (n = 6). OM failed to generate measurable changes in body weight (+2%; P = 0.1), or subcutaneous adiposity (+3%; P = 0.83) as assessed by magnetic resonance imaging (MRI). The removal of the greater omentum did not significantly reduce total visceral adipose volume (-7.3 +/- 6.4%; P = 0.29); although primary analysis showed a trend for OM to increase S(I) when compared to sham operated animals (P = 0.078), further statistical analysis revealed that this minor reduction in visceral fat alleviated insulin resistance by augmenting S(I) of the periphery (+67.7 +/- 35.2%; P = 0.03), as determined by the euglycemic-hyperinsulinemic clamp. Insulin secretory response during the hyperglycemic step clamp was not directly influenced by omental fat removal (presurgery 6.82 +/- 1.4 vs. postsurgery: 6.7 +/- 1.2 pmol/l/mg/dl, P = 0.9). These findings provide new evidence for the deleterious role of visceral fat in insulin resistance, and suggest that a greater OM procedure may effectively improve insulin sensitivity. PMID:19214178

  5. Depressive symptoms, insulin sensitivity and insulin secretion in the RISC cohort study

    NARCIS (Netherlands)

    Bot, M.; Pouwer, F.; De Jonge, P.; Nolan, J. J.; Mari, A.; Hojlund, K.; Golay, A.; Balkau, B.; Dekker, J. M.

    2013-01-01

    Aim. This study explored the association of depressive symptoms with indices of insulin sensitivity and insulin secretion in a cohort of non-diabetic men and women aged 30 to 64 years. Methods. The study population was derived from the 3-year follow-up of the Relationship between Insulin Sensitivity

  6. Depressive symptoms, insulin sensitivity and insulin secretion in the RISC cohort study

    DEFF Research Database (Denmark)

    Bot, M; Pouwer, F; De Jonge, P;

    2013-01-01

    AIM: This study explored the association of depressive symptoms with indices of insulin sensitivity and insulin secretion in a cohort of non-diabetic men and women aged 30 to 64 years. METHODS: The study population was derived from the 3-year follow-up of the Relationship between Insulin...... Sensitivity and Cardiovascular Disease Risk (RISC) study. Presence of significant depressive symptoms was defined as a Center for Epidemiologic Studies Depression Scale (CES-D) score ≥ 16. Standard oral glucose tolerance tests were performed. Insulin sensitivity was assessed with the oral glucose insulin...... sensitivity (OGIS) index. Insulin secretion was estimated using three model-based parameters of insulin secretion (beta-cell glucose sensitivity, the potentiation factor ratio, and beta-cell rate sensitivity). RESULTS: A total of 162 out of 1027 participants (16%) had significant depressive symptoms. Having...

  7. Insulin Sensitivity and Insulin Clearance are Heritable and Have Strong Genetic Correlation in Mexican Americans

    OpenAIRE

    Goodarzi, Mark O; Langefeld, Carl D.; Xiang, Anny H.; Chen, Yii-Der I.; Guo, Xiuqing; Hanley, Anthony J. G.; Raffel, Leslie J.; Kandeel, Fouad; Thomas A Buchanan; Norris, Jill M.; Fingerlin, Tasha E.; Lorenzo, Carlos; Rewers, Marian J; Haffner, Steven M.; Donald W Bowden

    2014-01-01

    Objective We describe the GUARDIAN (Genetics UndeRlying DIAbetes in HispaNics) consortium, along with heritability estimates and genetic and environmental correlations of insulin sensitivity and metabolic clearance rate of insulin (MCRI). Design and Methods GUARDIAN is comprised of seven cohorts, consisting of 4336 Mexican-American individuals in 1346 pedigrees. Insulin sensitivity (SI), MCRI, and acute insulin response (AIRg) were measured by frequently sampled intravenous glucose tolerance ...

  8. Current understanding of increased insulin sensitivity after exercise - emerging candidates

    DEFF Research Database (Denmark)

    Maarbjerg, Stine Just; Sylow, Lykke; Richter, Erik

    2011-01-01

    Exercise counteracts insulin resistance and improves glucose homeostasis in many ways. Apart from increasing muscle glucose uptake quickly, exercise also clearly increases muscle insulin sensitivity in the post exercise period. This review will focus on the mechanisms responsible for this increased...... signaling component in the insulin signaling pathway such as aPKC, Rac1, TBC1D4 and TBC1D1 have been described. These are all affected by both insulin and exercise which means that they are likely converging points in promoting GLUT4 translocation and therefore possible candidates for regulating insulin...... sensitivity after exercise. Whereas TBC1D1 does not appear to regulate insulin sensitivity after exercise, correlative evidence in contrast suggests TBC1D4 to be a relevant candidate. Little is known about aPKC and Rac1 in relation to insulin sensitivity after exercise. Besides mechanisms involved in...

  9. Effect of vanadium on insulin sensitivity and appetite.

    Science.gov (United States)

    Wang, J; Yuen, V G; McNeill, J H

    2001-06-01

    Vanadium, a potent nonselective inhibitor of protein tyrosine phosphatases, has been shown to mimic many of the metabolic actions of insulin both in vivo and in vitro. The mechanism(s) of the effect of vanadium on the decrease in appetite and body weight in Zucker fa/fa rats, an insulin-resistant model, is still unclear. Because insulin may inhibit hypothalamic neuropeptide Y (NPY), which is known to be related to appetite, and increase leptin secretion in adipose tissue, we studied the possibility that the changes in appetite produced by vanadium may be linked to altered NPY levels in the hypothalamus. We also examined effects of vanadium on leptin. Zucker lean and fatty rats were chronically treated with bis(maltolato)oxovanadium(IV) (BMOV), an organic vanadium compound, in the drinking water. Plasma and adipose tissue leptin levels were measured by radioimmunoassay and immunoblotting, respectively. Hypothalamic NPY mRNA and peptide levels were measured using in situ hybridization and immunocytochemistry, respectively. BMOV treatment significantly reduced food intake, body fat, body weight, plasma insulin levels, and glucose levels in fatty Zucker rats. Fifteen minutes after insulin injection (5 U/kg, intravenous [IV]), circulating leptin levels (+100%) and adipose leptin levels (+60%) were elevated in BMOV-treated fatty rats, although these effects were not observed in untreated fatty rats. NPY mRNA levels in the arcuate nucleus (ARC) (-29%), NPY peptide levels in ARC (-31%), as well as in the paraventricular nucleus (PVN) (-37%) were decreased with BMOV treatment in these fatty rats. These data indicate that BMOV may increase insulin sensitivity in adipose tissue and decrease appetite and body fat by decreasing NPY levels in the hypothalamus. BMOV-induced reduction in appetite and weight gain along with normalized insulin levels in models of obesity, suggest its possible use as a therapeutic agent in obesity.

  10. Fructose, but not glucose, impairs insulin signaling in the three major insulin-sensitive tissues

    OpenAIRE

    Miguel Baena; Gemma Sangüesa; Alberto Dávalos; María-Jesús Latasa; Aleix Sala-Vila; Rosa María Sánchez; Núria Roglans; Juan Carlos Laguna; Marta Alegret

    2016-01-01

    Human studies support the relationship between high intake of fructose-sweetened beverages and type 2 diabetes, but there is a debate on whether this effect is fructose-specific or it is merely associated to an excessive caloric intake. Here we investigate the effects of 2 months' supplementation to female rats of equicaloric 10% w/v fructose or glucose solutions on insulin sensitivity in target tissues. Fructose supplementation caused hepatic deposition of triglycerides and changed the fatty...

  11. Naltrexone effects on insulin sensitivity and insulin secretion in hyperandrogenic women.

    Science.gov (United States)

    Sir-Petermann, T; López, G; Castillo, T; Calvillán, M; Rabenbauer, B; Wildt, L

    1998-01-01

    A total of 12 women (24.2 +/- 1.6 years old, BMI 36.7 +/- 1.5 Kg/m2) with hyperandrogenism (HA) and with normal glucose tolerance test were studied to evaluate the involvement of endogenous opioids in the pathophysiology of insulin secretion and insulin sensitivity in HA by administering naltrexone, an oral opioid receptor antagonist. Six patients received naltrexone orally (75 mg daily) and another six received placebo for 12 weeks (double-blind study). Before and after therapy a frequently sampled intravenous glucose tolerance test (FSIVGTT) was performed. The insulin sensitivity index (SI) was determined by Bergman's program. SHBG, DHEAS, testosterone, free androgen index (FAI) and plasma concentrations of IGF-I and IGFBP-1 were determined in 3 basal samples, before and after therapy. Treatment with naltrexone in hyperandrogenic patients resulted in a decrease in fasting insulin concentrations of 40% and C-peptide concentrations of 50% (p naltrexone treatment of 34% for insulin and 35% for C-peptide. Insulin sensitivity did not change under naltrexone (1.26 +/- 0.19 vs 1.32 +/- 0.32 10(-4) x min(-1)/(uU/ml)) or placebo (0.95 +/- 0.19 vs 1.12 +/- 0.28 10(-4) x min(-1)/(uU/ml)) administration. However, glucose effectiveness increased significantly with naltrexone (2.231 +/- 0.002 vs 3.354 +/- 0.006 x 10(-2) min(-1)). Glucose (fasting and area under the curve) was not modified significantly after naltrexone administration. Baseline hormone levels were similar in the two groups, and they did not change after long-term treatment with naltrexone or placebo. In conclusion, these results support the hypothesis of elevated opioid tonus and increased insulin secretion as a possible mechanism of hyperinsulinism in a group of hyperandrogenic women of ovarian origin. This alteration could act as an additional factor in the pathogenesis of insulin resistance found in an important proportion of these patients. PMID:9831304

  12. The Insulin-Sensitive Side of SHIP2

    Directory of Open Access Journals (Sweden)

    Stephane Schurmans

    2001-01-01

    Full Text Available A substantial and increasing proportion of death and disability in the EU (and elsewhere is attributable to diseases associated with insulin resistance (i.e., decreased insulin sensitivity. Beside type II diabetes, other diseases like obesity, hypertension, atherosclerosis, hyperlipidaemia, polycystic ovarian syndrome, and acromegaly are indeed associated with insulin resistance [1].

  13. Plasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentration precedes a decrease in whole-body insulin sensitivity in humans

    DEFF Research Database (Denmark)

    Stefan, Norbert; Vozarova, Barbora; Funahashi, Tohru;

    2002-01-01

    -induced tyrosine phosphorylation of the insulin receptor (IR) and also increase whole-body insulin sensitivity. To further characterize the relationship between plasma adiponectin concentration and insulin sensitivity in humans, we examined 1) the cross-sectional association between plasma adiponectin......Adiponectin, the most abundant adipose-specific protein, has been found to be negatively associated with degree of adiposity and positively associated with insulin sensitivity in Pima Indians and other populations. Moreover, adiponectin administration to rodents has been shown to increase insulin...... concentration and skeletal muscle IR tyrosine phosphorylation and 2) the prospective effect of plasma adiponectin concentration at baseline on change in insulin sensitivity. Fasting plasma adiponectin concentration, body composition (hydrodensitometry or dual energy X-ray absorptiometry), insulin sensitivity...

  14. Anaphylaxis to subcutaneous neutral protamine Hagedorn insulin with simultaneous sensitization to protamine and insulin.

    Science.gov (United States)

    Blanco, C; Castillo, R; Quiralte, J; Delgado, J; García, I; de Pablos, P; Carrillo, T

    1996-06-01

    We report an insulin-treated diabetic patient who suffered, in a 2-month period, three severe anaphylactic reactions immediately after self-administered subcutaneous injections of neutral protamine Hagedorn (NPH) human recombinant-DNA insulin. These reactions consisted of local and systemic symptoms, including dyspnea and hypotension. A simultaneous sensitization to human insulin and to protamine was demonstrated, both by skin tests and by the determination of serum specific IgE. Suspecting protamine allergy, we performed a test dose to human lente insulin with perfect tolerance. After a 1-year follow-up with lente-insulin treatment, no reactions have occurred, despite treatment interruptions. Therefore, protamine IgE-mediated allergy probably caused our patient's reactions. In conclusion, protamine sensitization should be ruled out in any patient with a history of reactions to subcutaneous protamine-containing insulins, even if insulin sensitization is present. PMID:8837667

  15. Trans fatty acids, insulin sensitivity and type 2 diabetes

    OpenAIRE

    Risérus, Ulf

    2006-01-01

    Trans fatty acids (TFA) could affect cell membrane functions, and may therefore influence peripheral insulin sensitivity and the risk of developing type 2 diabetes. It is important to understand whether low amounts of TFA consumed during long periods may promote insulin resistance and have clinically relevant effects on diabetes risk. Data from controlled intervention studies examining the effects of TFA on insulin sensitivity and type 2 diabetes are reviewed. The results show no consistent e...

  16. Cross-Talk between PPARγ and Insulin Signaling and Modulation of Insulin Sensitivity

    Directory of Open Access Journals (Sweden)

    Anna Leonardini

    2009-01-01

    Full Text Available PPARγ activation in type 2 diabetic patients results in a marked improvement in insulin and glucose parameters, resulting from an improvement of whole-body insulin sensitivity. Adipose tissue is the major mediator of PPARγ action on insulin sensitivity. PPARγ activation in mature adipocytes induces the expression of a number of genes involved in the insulin signaling cascade, thereby improving insulin sensitivity. PPARγ is the master regulator of adipogenesis, thereby stimulating the production of small insulin-sensitive adipocytes. In addition to its importance in adipogenesis, PPARγ plays an important role in regulating lipid, metabolism in mature adipocytes by increasing fatty acid trapping. Finally, adipose tissue produces several cytokines that regulate energy homeostasis, lipid and glucose metabolism. Disturbances in the production of these factors may contribute to metabolic abnormalities, and PPARγ activation is also associated with beneficial effects on expression and secretion of a whole range of cytokines.

  17. Leptin therapy, insulin sensitivity, and glucose homeostasis

    Directory of Open Access Journals (Sweden)

    Gilberto Paz-Filho

    2012-01-01

    Full Text Available Glucose homeostasis is closely regulated not only by insulin, but also by leptin. Both hormones act centrally, regulating food intake and adiposity in humans. Leptin has several effects on the glucose-insulin homeostasis, some of which are independent of body weight and adiposity. Those effects of leptin are determined centrally in the hypothalamus and peripherally in the pancreas, muscles and liver. Leptin has beneficial effects on the glucose-insulin metabolism, by decreasing glycemia, insulinemia and insulin resistance. The understanding of the effects of leptin on the glucose-insulin homeostasis will lead to the development of leptin-based therapies against diabetes and other insulin resistance syndromes. In these review, we summarize the interactions between leptin and insulin, and their effects on the glucose metabolism.

  18. Role of AMPK in Regulating Muscle Insulin Sensitivity

    DEFF Research Database (Denmark)

    Kjøbsted, Rasmus

    exercise in healthy and insulin resistant skeletal muscle. This has been addressed in three studies that consist of various experimental procedures ranging from in vivo experiments in healthy obese and type 2 diabetic subjects to in situ and ex vivo experiments in AMPK-deficient mouse models. Results...... signaling in skeletal muscle of type 2 diabetic patients in response to exercise. Interestingly, we observe that AMPK activity and phosphorylation of TBC1D4 Ser318, Ser341 and Ser704 are increased 3 hours into exercise recovery - a time point when post-exercise improvements in muscle insulin sensitivity......The ability of insulin to stimulate skeletal muscle glucose uptake is instrumental for controlling whole-body glucose homeostasis. Decreased peripheral sensitivity to insulin increases the risk of developing type 2 diabetes. Insulin sensitivity can be defined as the concentration of insulin...

  19. High intensity interval training improves liver and adipose tissue insulin sensitivity

    Directory of Open Access Journals (Sweden)

    Katarina Marcinko

    2015-12-01

    Conclusions: These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC.

  20. Fructose, but not glucose, impairs insulin signaling in the three major insulin-sensitive tissues.

    Science.gov (United States)

    Baena, Miguel; Sangüesa, Gemma; Dávalos, Alberto; Latasa, María-Jesús; Sala-Vila, Aleix; Sánchez, Rosa María; Roglans, Núria; Laguna, Juan Carlos; Alegret, Marta

    2016-05-19

    Human studies support the relationship between high intake of fructose-sweetened beverages and type 2 diabetes, but there is a debate on whether this effect is fructose-specific or it is merely associated to an excessive caloric intake. Here we investigate the effects of 2 months' supplementation to female rats of equicaloric 10% w/v fructose or glucose solutions on insulin sensitivity in target tissues. Fructose supplementation caused hepatic deposition of triglycerides and changed the fatty acid profile of this fraction, with an increase in monounsaturated and a decrease in polyunsaturated species, but did not cause inflammation and oxidative stress. Fructose but not glucose-supplemented rats displayed an abnormal glucose tolerance test, and did not show increased phosphorylation of V-akt murine thymoma viral oncogene homolog-2 (Akt) in white adipose tissue and liver after insulin administration. In skeletal muscle, phosphorylation of Akt and of Akt substrate of 160 kDA (AS160) was not impaired but the expression of the glucose transporter type 4 (GLUT4) in the plasma membrane was reduced only in fructose-fed rats. In conclusion, fructose but not glucose supplementation causes fatty liver without inflammation and oxidative stress and impairs insulin signaling in the three major insulin-responsive tissues independently from the increase in energy intake.

  1. Fructose, but not glucose, impairs insulin signaling in the three major insulin-sensitive tissues.

    Science.gov (United States)

    Baena, Miguel; Sangüesa, Gemma; Dávalos, Alberto; Latasa, María-Jesús; Sala-Vila, Aleix; Sánchez, Rosa María; Roglans, Núria; Laguna, Juan Carlos; Alegret, Marta

    2016-01-01

    Human studies support the relationship between high intake of fructose-sweetened beverages and type 2 diabetes, but there is a debate on whether this effect is fructose-specific or it is merely associated to an excessive caloric intake. Here we investigate the effects of 2 months' supplementation to female rats of equicaloric 10% w/v fructose or glucose solutions on insulin sensitivity in target tissues. Fructose supplementation caused hepatic deposition of triglycerides and changed the fatty acid profile of this fraction, with an increase in monounsaturated and a decrease in polyunsaturated species, but did not cause inflammation and oxidative stress. Fructose but not glucose-supplemented rats displayed an abnormal glucose tolerance test, and did not show increased phosphorylation of V-akt murine thymoma viral oncogene homolog-2 (Akt) in white adipose tissue and liver after insulin administration. In skeletal muscle, phosphorylation of Akt and of Akt substrate of 160 kDA (AS160) was not impaired but the expression of the glucose transporter type 4 (GLUT4) in the plasma membrane was reduced only in fructose-fed rats. In conclusion, fructose but not glucose supplementation causes fatty liver without inflammation and oxidative stress and impairs insulin signaling in the three major insulin-responsive tissues independently from the increase in energy intake. PMID:27194405

  2. Butyrate Improves Insulin Sensitivity and Increases Energy Expenditure in Mice

    OpenAIRE

    Gao, Zhanguo; Yin, Jun; Zhang, Jin; Ward, Robert E.; Martin, Roy J; Lefevre, Michael; Cefalu, William T.; Ye, Jianping

    2009-01-01

    OBJECTIVE We examined the role of butyric acid, a short-chain fatty acid formed by fermentation in the large intestine, in the regulation of insulin sensitivity in mice fed a high-fat diet. RESEARCH DESIGN AND METHODS In dietary-obese C57BL/6J mice, sodium butyrate was administrated through diet supplementation at 5% wt/wt in the high-fat diet. Insulin sensitivity was examined with insulin tolerance testing and homeostasis model assessment for insulin resistance. Energy metabolism was monitor...

  3. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage.

    Science.gov (United States)

    Muniyappa, Ranganath; Lee, Sihoon; Chen, Hui; Quon, Michael J

    2008-01-01

    Insulin resistance contributes to the pathophysiology of diabetes and is a hallmark of obesity, metabolic syndrome, and many cardiovascular diseases. Therefore, quantifying insulin sensitivity/resistance in humans and animal models is of great importance for epidemiological studies, clinical and basic science investigations, and eventual use in clinical practice. Direct and indirect methods of varying complexity are currently employed for these purposes. Some methods rely on steady-state analysis of glucose and insulin, whereas others rely on dynamic testing. Each of these methods has distinct advantages and limitations. Thus, optimal choice and employment of a specific method depends on the nature of the studies being performed. Established direct methods for measuring insulin sensitivity in vivo are relatively complex. The hyperinsulinemic euglycemic glucose clamp and the insulin suppression test directly assess insulin-mediated glucose utilization under steady-state conditions that are both labor and time intensive. A slightly less complex indirect method relies on minimal model analysis of a frequently sampled intravenous glucose tolerance test. Finally, simple surrogate indexes for insulin sensitivity/resistance are available (e.g., QUICKI, HOMA, 1/insulin, Matusda index) that are derived from blood insulin and glucose concentrations under fasting conditions (steady state) or after an oral glucose load (dynamic). In particular, the quantitative insulin sensitivity check index (QUICKI) has been validated extensively against the reference standard glucose clamp method. QUICKI is a simple, robust, accurate, reproducible method that appropriately predicts changes in insulin sensitivity after therapeutic interventions as well as the onset of diabetes. In this Frontiers article, we highlight merits, limitations, and appropriate use of current in vivo measures of insulin sensitivity/resistance. PMID:17957034

  4. Leptin therapy, insulin sensitivity, and glucose homeostasis

    OpenAIRE

    Gilberto Paz-Filho; Claudio Mastronardi; Ma-Li Wong; Julio Licinio

    2012-01-01

    Glucose homeostasis is closely regulated not only by insulin, but also by leptin. Both hormones act centrally, regulating food intake and adiposity in humans. Leptin has several effects on the glucose-insulin homeostasis, some of which are independent of body weight and adiposity. Those effects of leptin are determined centrally in the hypothalamus and peripherally in the pancreas, muscles and liver. Leptin has beneficial effects on the glucose-insulin metabolism, by decreasing glycemia, insu...

  5. Insulin sensitivity and metabolic flexibility following exercise training among different obese insulin resistant phenotypes

    DEFF Research Database (Denmark)

    Malin, Steven K; Haus, Jacob M; Solomon, Thomas;

    2013-01-01

    Impaired fasting glucose (IFG) blunts the reversal of impaired glucose tolerance (IGT) after exercise training. Metabolic inflexibility has been implicated in the etiology of insulin resistance, however, the efficacy of exercise on peripheral and hepatic insulin sensitivity or substrate utilization......) and were instructed to maintain a eucaloric diet. A euglycemic-hyperinsulinemic clamp (40 mU/m(2)/min) with [6,6-(2)H]-glucose was used to determine peripheral and hepatic insulin sensitivity. Non-oxidative glucose disposal and metabolic flexibility (insulin-stimulated respiratory quotient [RQ] minus...

  6. Mechanisms of human insulin resistance and thiazolidinedione-mediated insulin sensitization

    Science.gov (United States)

    Sears, D. D.; Hsiao, G.; Hsiao, A.; Yu, J. G.; Courtney, C. H.; Ofrecio, J. M.; Chapman, J.; Subramaniam, S.

    2009-01-01

    Cellular and tissue defects associated with insulin resistance are coincident with transcriptional abnormalities and are improved after insulin sensitization with thiazolidinedione (TZD) PPARγ ligands. We characterized 72 human subjects by relating their clinical phenotypes with functional pathway alterations. We transcriptionally profiled 364 biopsies harvested before and after hyperinsulinemic-euglycemic clamp studies, at baseline and after 3-month TZD treatment. We have identified molecular and functional characteristics of insulin resistant subjects and distinctions between TZD treatment responder and nonresponder subjects. Insulin resistant subjects exhibited alterations in skeletal muscle (e.g., glycolytic flux and intramuscular adipocytes) and adipose tissue (e.g., mitochondrial metabolism and inflammation) that improved relative to TZD-induced insulin sensitization. Pre-TZD treatment expression of MLXIP in muscle and HLA-DRB1 in adipose tissue from insulin resistant subjects was linearly predictive of post-TZD insulin sensitization. We have uniquely characterized coordinated cellular and tissue functional pathways that are characteristic of insulin resistance, TZD-induced insulin sensitization, and potential TZD responsiveness. PMID:19841271

  7. Greater omentectomy improves insulin sensitivity in non-obese dogs

    OpenAIRE

    Lottati, Maya; Kolka, Cathryn M; Stefanovski, Darko; Kirkman, Erlinda L.; Bergman, Richard N

    2009-01-01

    Visceral adiposity is strongly associated with insulin resistance; however little evidence directly demonstrates that visceral fat per se impairs insulin action. Here we examine the effects of the surgical removal of the greater omentum and its occupying visceral fat, an omentectomy, on insulin sensitivity (SI) and β-cell function in non-obese dogs. Thirteen male mongrel dogs were used in the present research study; animals were randomly assigned to surgical treatment with either omentectomy ...

  8. Exercise, pregnancy, and insulin sensitivity--what is new?

    DEFF Research Database (Denmark)

    Damm, Peter; Breitowicz, Bettina; Hegaard, Hanne

    2007-01-01

    Pregnancy is characterized by a marked physiological insulin resistance. Overweight and obesity or lack of physical activity can aggravate this reduced insulin sensitivity further. Increased insulin resistance has been associated with serious pregnancy complications, such as gestational diabetes...... mellitus (GDM) and pre-eclampsia. Recent studies clearly indicate that physical activity before and during pregnancy can reduce the risk of GDM and pre-eclampsia....

  9. Low fish oil intake improves insulin sensitivity, lipid profile and muscle metabolism on insulin resistant MSG-obese rats

    Directory of Open Access Journals (Sweden)

    Iagher Fabiola

    2011-04-01

    Full Text Available Abstract Background Obesity is commonly associated with diabetes, cardiovascular diseases and cancer. The purpose of this study was to determinate the effect of a lower dose of fish oil supplementation on insulin sensitivity, lipid profile, and muscle metabolism in obese rats. Methods Monosodium glutamate (MSG (4 mg/g body weight was injected in neonatal Wistar male rats. Three-month-old rats were divided in normal-weight control group (C, coconut fat-treated normal weight group (CO, fish oil-treated normal weight group (FO, obese control group (Ob, coconut fat-treated obese group (ObCO and fish oil-treated obese group (ObFO. Obese insulin-resistant rats were supplemented with fish oil or coconut fat (1 g/kg/day for 4 weeks. Insulin sensitivity, fasting blood biochemicals parameters, and skeletal muscle glucose metabolism were analyzed. Results Obese animals (Ob presented higher Index Lee and 2.5 fold epididymal and retroperitoneal adipose tissue than C. Insulin sensitivity test (Kitt showed that fish oil supplementation was able to maintain insulin sensitivity of obese rats (ObFO similar to C. There were no changes in glucose and HDL-cholesterol levels amongst groups. Yet, ObFO revealed lower levels of total cholesterol (TC; 30% and triacylglycerol (TG; 33% compared to Ob. Finally, since exposed to insulin, ObFO skeletal muscle revealed an increase of 10% in lactate production, 38% in glycogen synthesis and 39% in oxidation of glucose compared to Ob. Conclusions Low dose of fish oil supplementation (1 g/kg/day was able to reduce TC and TG levels, in addition to improved systemic and muscle insulin sensitivity. These results lend credence to the benefits of n-3 fatty acids upon the deleterious effects of insulin resistance mechanisms.

  10. The Adipose Transcriptional Response to Insulin Is Determined by Obesity, Not Insulin Sensitivity

    DEFF Research Database (Denmark)

    Rydén, Mikael; Hrydziuszko, Olga; Mileti, Enrichetta;

    2016-01-01

    Metabolically healthy obese subjects display preserved insulin sensitivity and a beneficial white adipose tissue gene expression pattern. However, this observation stems from fasting studies when insulin levels are low. We investigated adipose gene expression by 5'Cap-mRNA sequencing in 17 healthy...... non-obese (NO), 21 insulin-sensitive severely obese (ISO), and 30 insulin-resistant severely obese (IRO) subjects, before and 2 hr into a hyperinsulinemic euglycemic clamp. ISO and IRO subjects displayed a clear but globally similar transcriptional response to insulin, which differed from the small...... that differences in the acute transcriptional response to insulin are primarily driven by obesity per se, challenging the notion of healthy obese adipose tissue, at least in severe obesity....

  11. Influence of obesity and insulin sensitivity on insulin signaling genes in human omental and subcutaneous adipose tissue.

    Science.gov (United States)

    MacLaren, R; Cui, W; Simard, S; Cianflone, K

    2008-02-01

    Obesity and insulin resistance are independent risk factors for metabolic syndrome, diabetes, and cardiovascular disease. Adipose tissue samples from nonobese (NO), insulin-sensitive obese (ISO), and insulin-resistant obese (IRO) subjects from subcutaneous (SC) and omental (OM) adipose tissue (n = 28) were analyzed by microarray and confirmed by real-time PCR. Insulin signaling gene expression changes were greater in OM than in SC tissue and were related to insulin resistance rather than to obesity; few genes correlated with body mass index. Insulin receptor and insulin receptor substrate 1 (IRS-1) increased in the IRO versus pooled insulin-sensitive (NO+ISO) subjects. In glucose transport, PI3Kalpha and PDK2 decreased in IRO subjects, whereas PI3Kgamma, Akt2, GLUT4, and GLUT1 increased. IRS-1 regulators Jnk and IKK increased in IRO (P < 0.01 and P < 0.001 respectively). In protein synthesis, most genes examined were downregulated in IRO subjects, including mTor, Rheb, and 4EBP and eIF members (all P < 0.05). In proliferation, SHC, SOS, and Raf1 (P < 0.05) were increased, whereas Ras and MEK1/2 kinase 1 (P < 0.05) were decreased, in IRO subjects. Finally, in differentiation, PPARgamma, CEBPalpha, and CEBPbeta decreased, whereas PPARdelta, CEBPgamma, and CEBPepsilon increased, in IRO subjects (P < 0.05). Together, microarray and real-time PCR data demonstrate that insulin resistance rather than obesity is associated with altered gene expression of insulin signaling genes, especially in OM adipose tissue. PMID:17986714

  12. Insulin sensitivity in clinically healthy individuals with microalbuminuria

    DEFF Research Database (Denmark)

    Jensen, J S; Borch-Johnsen, K; Jensen, G;

    1996-01-01

    excretion rate (UAER) of 6.6 to 150 micrograms/min) and 24 age- and sex-matched controls with normoalbuminuria (UAER body weight x min). Insulin sensitivity...... (whole body glucose disposal) was similar in the two groups ((mean (95% C.I.)) 351 (321-381) vs. 364 (339-388) mg/(m2 x min); P = 0.51). Among urinary albumin excretion rate, blood pressure, serum lipid concentrations, body mass index waist-hip ratio, fasting concentrations of serum insulin and blood...... glucose, tobacco and alcohol consumption, physical activity, and age and sex, fasting serum insulin concentration was the only variable independently associated with insulin sensitivity (r = -0.55; P = 0.0001). It is concluded that microalbuminuria is not associated with impaired insulin sensitivity...

  13. Chromium and Polyphenols From Cinnamon Improve Insulin Sensitivity

    Science.gov (United States)

    Naturally occurring compounds that have been shown to improve insulin sensitivity include chromium and polyphenols found in cinnamon. These compounds also have similar effects on insulin signaling and glucose control. The signs of chromium deficiency are similar to those for the metabolic syndrome ...

  14. Mechanisms of human insulin resistance and thiazolidinedione-mediated insulin sensitization

    OpenAIRE

    Sears, D. D.; Hsiao, G.; Hsiao, A.; Yu, J. G.; Courtney, C. H.; J.M. Ofrecio; Chapman, J; Subramaniam, S

    2009-01-01

    Cellular and tissue defects associated with insulin resistance are coincident with transcriptional abnormalities and are improved after insulin sensitization with thiazolidinedione (TZD) PPARγ ligands. We characterized 72 human subjects by relating their clinical phenotypes with functional pathway alterations. We transcriptionally profiled 364 biopsies harvested before and after hyperinsulinemic-euglycemic clamp studies, at baseline and after 3-month TZD treatment. We have identified molecula...

  15. Hormone-sensitive lipase null mice exhibit signs of impaired insulin sensitivity whereas insulin secretion is intact

    DEFF Research Database (Denmark)

    Mulder, Hindrik; Sörhede-Winzell, Maria; Contreras, Juan Antonio;

    2003-01-01

    Lipid metabolism plays an important role in glucose homeostasis under normal and pathological conditions. In adipocytes, skeletal muscle, and pancreatic beta-cells, lipids are mobilized from acylglycerides by the hormone-sensitive lipase (HSL). Here, the consequences of a targeted disruption...... of the HSL gene for glucose homeostasis were examined. HSL null mice were slightly hyperglycemic in the fasted, but not fed state, which was accompanied by moderate hyperinsulinemia. During glucose challenges, however, disposal of the sugar was not affected in HSL null mice, presumably because of release...... of increased amounts of insulin. Impaired insulin sensitivity was further indicated by retarded glucose disposal during an insulin tolerance test. A euglycemic hyperinsulinemic clamp revealed that hepatic glucose production was insufficiently blocked by insulin in HSL null mice. In vitro, insulin...

  16. Lipid-anthropometric index optimization for insulin sensitivity estimation

    Science.gov (United States)

    Velásquez, J.; Wong, S.; Encalada, L.; Herrera, H.; Severeyn, E.

    2015-12-01

    Insulin sensitivity (IS) is the ability of cells to react due to insulińs presence; when this ability is diminished, low insulin sensitivity or insulin resistance (IR) is considered. IR had been related to other metabolic disorders as metabolic syndrome (MS), obesity, dyslipidemia and diabetes. IS can be determined using direct or indirect methods. The indirect methods are less accurate and invasive than direct and they use glucose and insulin values from oral glucose tolerance test (OGTT). The accuracy is established by comparison using spearman rank correlation coefficient between direct and indirect method. This paper aims to propose a lipid-anthropometric index which offers acceptable correlation to insulin sensitivity index for different populations (DB1=MS subjects, DB2=sedentary without MS subjects and DB3=marathoners subjects) without to use OGTT glucose and insulin values. The proposed method is parametrically optimized through a random cross-validation, using the spearman rank correlation as comparator with CAUMO method. CAUMO is an indirect method designed from a simplification of the minimal model intravenous glucose tolerance test direct method (MINMOD-IGTT) and with acceptable correlation (0.89). The results show that the proposed optimized method got a better correlation with CAUMO in all populations compared to non-optimized. On the other hand, it was observed that the optimized method has better correlation with CAUMO in DB2 and DB3 groups than HOMA-IR method, which is the most widely used for diagnosing insulin resistance. The optimized propose method could detect incipient insulin resistance, when classify as insulin resistant subjects that present impaired postprandial insulin and glucose values.

  17. Insulin sensitivity : modulation by neuropeptides and hormones

    NARCIS (Netherlands)

    Hoek, Anita van den

    2006-01-01

    Nowadays, obesity has reached epidemic proportions globally. It can lead to several chronic diseases, including insulin resistance/type 2 diabetes mellitus. Feeding behaviour is regulated in the hypothalamus of the brain by two opposing pathways: NPY/AgRP neurons vs. POMC/CART neurons. In addition,

  18. Insulin and Insulin-Sensitizing Drugs in Neurodegeneration: Mitochondria as Therapeutic Targets

    Directory of Open Access Journals (Sweden)

    Paula I. Moreira

    2009-12-01

    Full Text Available Insulin, besides its glucose lowering effects, is involved in the modulation of lifespan, aging and memory and learning processes. As the population ages, neurodegenerative disorders become epidemic and a connection between insulin signaling dysregulation, cognitive decline and dementia has been established. Mitochondria are intracellular organelles that despite playing a critical role in cellular metabolism are also one of the major sources of reactive oxygen species. Mitochondrial dysfunction, oxidative stress and neuroinflammation, hallmarks of neurodegeneration, can result from impaired insulin signaling. Insulin-sensitizing drugs such as the thiazolidinediones are a new class of synthetic compounds that potentiate insulin action in the target tissues and act as specific agonists of the peroxisome proliferator-activated receptor gamma (PPAR-γ. Recently, several PPAR agonists have been proposed as novel and possible therapeutic agents for neurodegenerative disorders. Indeed, the literature shows that these agents are able to protect against mitochondrial dysfunction, oxidative damage, inflammation and apoptosis. This review discusses the role of mitochondria and insulin signaling in normal brain function and in neurodegeneration. Furthermore, the potential protective role of insulin and insulin sensitizers in Alzheimer´s, Parkinson´s and Huntington´s diseases and amyotrophic lateral sclerosis will be also discussed.

  19. Adipose Cell Size and Regional Fat Deposition as Predictors of Metabolic Response to Overfeeding in Insulin-Resistant and Insulin-Sensitive Humans.

    Science.gov (United States)

    McLaughlin, Tracey; Craig, Colleen; Liu, Li-Fen; Perelman, Dalia; Allister, Candice; Spielman, Daniel; Cushman, Samuel W

    2016-05-01

    Obesity is associated with insulin resistance, but significant variability exists between similarly obese individuals, pointing to qualitative characteristics of body fat as potential mediators. To test the hypothesis that obese, insulin-sensitive (IS) individuals possess adaptive adipose cell/tissue responses, we measured subcutaneous adipose cell size, insulin suppression of lipolysis, and regional fat responses to short-term overfeeding in BMI-matched overweight/obese individuals classified as IS or insulin resistant (IR). At baseline, IR subjects exhibited significantly greater visceral adipose tissue (VAT), intrahepatic lipid (IHL), plasma free fatty acids, adipose cell diameter, and percentage of small adipose cells. With weight gain (3.1 ± 1.4 kg), IR subjects demonstrated no significant change in adipose cell size, VAT, or insulin suppression of lipolysis and only 8% worsening of insulin-mediated glucose uptake (IMGU). Alternatively, IS subjects demonstrated significant adipose cell enlargement; decrease in the percentage of small adipose cells; increase in VAT, IHL, and lipolysis; 45% worsening of IMGU; and decreased expression of lipid metabolism genes. Smaller baseline adipose cell size and greater enlargement with weight gain predicted decline in IMGU, as did increase in IHL and VAT and decrease in insulin suppression of lipolysis. Weight gain in IS humans causes maladaptive changes in adipose cells, regional fat distribution, and insulin resistance. The correlation between development of insulin resistance and changes in adipose cell size, VAT, IHL, and insulin suppression of lipolysis highlight these factors as potential mediators between obesity and insulin resistance. PMID:26884438

  20. Differential insulin sensitivities of glucose, amino acid, and albumin metabolism in elderly men and women.

    Science.gov (United States)

    Boirie, Y; Gachon, P; Cordat, N; Ritz, P; Beaufrère, B

    2001-02-01

    Regulation of glucose homeostasis by insulin is modified during aging, but whether this alteration is associated with changes in protein metabolism is less defined. Insulin dose responses of whole body glucose, leucine, and albumin metabolism have been investigated using isotopic dilution of D-[6, 6-(2)H(2)]glucose and L-[1-(13)C]leucine in 14 young (Y; 24.0 +/- 0.9 yr; mean +/- SEM, 20.5 +/- 0.4 kg/m(2)) and 12 healthy elderly subjects (E; 69.4 +/- 0.6 yr; 24.6 +/- 0.8 kg/m(2)) using a euglycemic and euaminoacidemic hyperinsulinemic clamp at two insulin infusion rates of 0.2 and 0.5 mU/kg.min (CL1 and CL2, respectively). Despite significantly higher plasma insulin in E than in Y, the glucose disposal rate was lower in E than in Y at both insulin levels, whereas glucose production was normally suppressed. Whole body protein breakdown was less inhibited by insulin in E than in Y at CL1 (-13.5 +/- 1.4% vs. -8.8 +/- 1.3%, Y vs. E, P CL2 (-22.0 +/- 1.4% vs. -18.8 +/- 1.7%, Y vs. E, P = NS). The albumin synthesis rate was identical and stimulated to the same extent by insulin in groups Y and E. Gender affected basal leucine metabolism, but the response to insulin was similar in both groups. In conclusion, decreased insulin action on glucose disposal is associated with a reduced insulin sensitivity for protein breakdown in healthy elderly subjects at low insulin concentrations. Higher insulin levels compensate for a reduced insulin action on protein metabolism in elderly subjects. PMID:11158022

  1. High levels of dietary stearate promote adiposity and deteriorate hepatic insulin sensitivity

    Directory of Open Access Journals (Sweden)

    Havekes Louis M

    2010-03-01

    Full Text Available Abstract Background Relatively little is known about the role of specific saturated fatty acids in the development of high fat diet induced obesity and insulin resistance. Here, we have studied the effect of stearate in high fat diets (45% energy as fat on whole body energy metabolism and tissue specific insulin sensitivity. Methods C57Bl/6 mice were fed a low stearate diet based on palm oil or one of two stearate rich diets, one diet based on lard and one diet based on palm oil supplemented with tristearin (to the stearate level of the lard based diet, for a period of 5 weeks. Ad libitum fed Oxidative metabolism was assessed by indirect calorimetry at week 5. Changes in body mass and composition was assessed by DEXA scan analysis. Tissue specific insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp analysis and Western blot at the end of week 5. Results Indirect calorimetry analysis revealed that high levels of dietary stearate resulted in lower caloric energy expenditure characterized by lower oxidation of fatty acids. In agreement with this metabolic phenotype, mice on the stearate rich diets gained more adipose tissue mass. Whole body and tissue specific insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp and analysis of insulin induced PKBser473 phosphorylation. Whole body insulin sensitivity was decreased by all high fat diets. However, while insulin-stimulated glucose uptake by peripheral tissues was impaired by all high fat diets, hepatic insulin sensitivity was affected only by the stearate rich diets. This tissue-specific pattern of reduced insulin sensitivity was confirmed by similar impairment in insulin-induced phosphorylation of PKBser473 in both liver and skeletal muscle. Conclusion In C57Bl/6 mice, 5 weeks of a high fat diet rich in stearate induces a metabolic state favoring low oxidative metabolism, increased adiposity and whole body insulin resistance characterized by severe hepatic insulin

  2. Insulin sensitivity: modulation by neuropeptides and hormones

    OpenAIRE

    Hoek, Anita van den

    2006-01-01

    Nowadays, obesity has reached epidemic proportions globally. It can lead to several chronic diseases, including insulin resistance/type 2 diabetes mellitus. Feeding behaviour is regulated in the hypothalamus of the brain by two opposing pathways: NPY/AgRP neurons vs. POMC/CART neurons. In addition, there are numerous peripheral signals, deriving from stomach, gut, pancreas and adipose tissue, that act on the hypothalamus and thereby contribute to the regulation of food intake. The aim of the ...

  3. AMPK and Exercise: Glucose Uptake and Insulin Sensitivity

    OpenAIRE

    Hayley M O'Neill

    2013-01-01

    AMPK is an evolutionary conserved sensor of cellular energy status that is activated during exercise. Pharmacological activation of AMPK promotes glucose uptake, fatty acid oxidation, mitochondrial biogenesis, and insulin sensitivity; processes that are reduced in obesity and contribute to the development of insulin resistance. AMPK deficient mouse models have been used to provide direct genetic evidence either supporting or refuting a role for AMPK in regulating these processes. Exercise pro...

  4. Maternal Glucose Tolerance in Pregnancy Affects Fetal Insulin Sensitivity

    OpenAIRE

    Luo, Zhong-Cheng; Delvin, Edgard; Fraser, William D.; Audibert, Francois; Deal, Cheri I.; Julien, Pierre; Girard, Isabelle; Shear, Roberta; Levy, Emile; Nuyt, Anne-Monique

    2010-01-01

    OBJECTIVE Offspring of mothers with impaired glucose tolerance are far more likely to develop type 2 diabetes. We tested the hypothesis that maternal glucose tolerance in pregnancy affects fetal insulin sensitivity or β-cell function. RESEARCH DESIGN AND METHODS In a prospective singleton pregnancy cohort study, we analyzed glucose, insulin, and proinsulin concentrations in maternal blood at the 50-g oral glucose tolerance test (OGTT) at 24–28 weeks of gestation and in venous cord blood (n = ...

  5. Circulating docosahexaenoic acid levels are associated with fetal insulin sensitivity.

    Directory of Open Access Journals (Sweden)

    Jin-Ping Zhao

    Full Text Available BACKGROUND: Arachidonic acid (AA; C20∶4 n-6 and docosahexaenoic acid (DHA; C22∶6 n-3 are important long-chain polyunsaturated fatty acids (LC-PUFA in maintaining pancreatic beta-cell structure and function. Newborns of gestational diabetic mothers are more susceptible to the development of type 2 diabetes in adulthood. It is not known whether low circulating AA or DHA is involved in perinatally "programming" this susceptibility. This study aimed to assess whether circulating concentrations of AA, DHA and other fatty acids are associated with fetal insulin sensitivity or beta-cell function, and whether low circulating concentrations of AA or DHA are involved in compromised fetal insulin sensitivity in gestational diabetic pregnancies. METHODS AND PRINCIPAL FINDINGS: In a prospective singleton pregnancy cohort, maternal (32-35 weeks gestation and cord plasma fatty acids were assessed in relation to surrogate indicators of fetal insulin sensitivity (cord plasma glucose-to-insulin ratio, proinsulin concentration and beta-cell function (proinsulin-to-insulin ratio in 108 mother-newborn pairs. Cord plasma DHA levels (in percentage of total fatty acids were lower comparing newborns of gestational diabetic (n = 24 vs. non-diabetic pregnancies (2.9% vs. 3.5%, P = 0.01. Adjusting for gestational age at blood sampling, lower cord plasma DHA levels were associated with lower fetal insulin sensitivity (lower glucose-to-insulin ratio, r = 0.20, P = 0.036; higher proinsulin concentration, r = -0.37, P <0.0001. The associations remained after adjustment for maternal and newborn characteristics. Cord plasma saturated fatty acids C18∶0 and C20∶0 were negatively correlated with fetal insulin sensitivity, but their levels were not different between gestational diabetic and non-diabetic pregnancies. Cord plasma AA levels were not correlated with fetal insulin sensitivity. CONCLUSION: Low circulating DHA levels are associated with

  6. Fast track surgery accelerates the recovery of postoperative insulin sensitivity

    Institute of Scientific and Technical Information of China (English)

    YANG Dong-jie; ZHANG Chang-hua; HE Yu-long; ZHANG Sheng; HE Wei-ling; CHEN Hua-yun; CAI Shi-rong; CHEN Chuang-qi; SONG Xin-ming; CUI Ji; MA Jin-ping

    2012-01-01

    Background Few clinical studies or randomized clinical trial results have reported the impact of fast track surgery on postoperative insulin sensitivity.This study aimed to investigate the effects of fast track surgery on postoperative insulin sensitivity in patients undergoing elective open colorectal resection.Methods Controlled,randomized clinical trial was conducted from November 2008 to January 2009 with one-month post-discharge follow-up.Seventy patients with colorectal carcinoma requiring colorectal resection were randomized into two groups:a fast track group (35 cases) and a conventional care group (35 cases).All included patients received elective open colorectal resection with combined tracheal intubation and general anesthesia.Clinical parameters (complication rates,return of gastrointestinal function and postoperative length of stay),stress index and insulin sensitivity were evaluated in both groups perioperatively.Reaults Sixty-two patients finally completed the study,32 cases in the fast-track group and 30 cases in the conventional care group.Our findings revealed a significantly faster recovery of postoperative insulin sensitivity on postoperative day 7 in the fast-track group than that in the conventional care group.We also found a significantly shorter length of postoperative stay and a significantly faster return of gastrointestinal function in patients undergoing fast-track rehabilitation.Conclusion Fast track surgery accelerates the recovery of postoperative insulin sensitivity in elective surgery for colorectal carcinoma with a shorter length of postoperative hospital stay.

  7. Grizzly bears exhibit augmented insulin sensitivity while obese prior to a reversible insulin resistance during hibernation.

    Science.gov (United States)

    Nelson, O Lynne; Jansen, Heiko T; Galbreath, Elizabeth; Morgenstern, Kurt; Gehring, Jamie Lauren; Rigano, Kimberly Scott; Lee, Jae; Gong, Jianhua; Shaywitz, Adam J; Vella, Chantal A; Robbins, Charles T; Corbit, Kevin C

    2014-08-01

    The confluence of obesity and diabetes as a worldwide epidemic necessitates the discovery of new therapies. Success in this endeavor requires translatable preclinical studies, which traditionally employ rodent models. As an alternative approach, we explored hibernation where obesity is a natural adaptation to survive months of fasting. Here we report that grizzly bears exhibit seasonal tripartite insulin responsiveness such that obese animals augment insulin sensitivity but only weeks later enter hibernation-specific insulin resistance (IR) and subsequently reinitiate responsiveness upon awakening. Preparation for hibernation is characterized by adiposity coupled to increased insulin sensitivity via modified PTEN/AKT signaling specifically in adipose tissue, suggesting a state of "healthy" obesity analogous to humans with PTEN haploinsufficiency. Collectively, we show that bears reversibly cope with homeostatic perturbations considered detrimental to humans and describe a mechanism whereby IR functions not as a late-stage metabolic adaptation to obesity, but rather a gatekeeper of the fed-fasting transition.

  8. Insulin-Sensitizing Agents and Polycystic Ovarian Syndrome

    Science.gov (United States)

    ... in facial and body hair, increased weight, and infertility. Diagnosis is made on a combination of clinical, ... options to treat insulin resistance? Weight loss, improved nutrition, and exercise are very important. Behavioral change should ...

  9. Prediction of the insulin sensitivity index using Bayesian networks

    DEFF Research Database (Denmark)

    Bøttcher, Susanne Gammelgaard; Dethlefsen, Claus

    The insulin sensitivity index () can be used in assessing the risk of developing type 2 diabetes. An intravenous study is used to determine using Bergmans minimal model. However, an intravenous study is time consuming and expensive and therefore not suitable for large scale epidemiological studies....... In this paper we learn the parameters and structure of several Bayesian networks relating measurements from an oral glucose tolerance test to the insulin sensitivity index determined from an intravenous study on the same individuals. The networks can then be used in prediction of from an oral glucose tolerance...

  10. Peripheral glucose metabolism and insulin sensitivity in Alzheimer's disease.

    Science.gov (United States)

    Kilander, L; Boberg, M; Lithell, H

    1993-04-01

    Twenty-four patients with Alzheimer's disease and matched controls were examined with reference to metabolic parameters such as peripheral insulin and glucose metabolism, serum lipid concentrations and blood pressure levels. Blood glucose levels and insulin response were measured during an intravenous glucose tolerance test and peripheral insulin sensitivity was estimated with the hyperinsulinemic euglycemic clamp technique. There were no differences recorded between the two groups in glucose metabolism, triglyceride, cholesterol or HDL-cholesterol levels. The patients with Alzheimer's disease had significantly lower blood pressure levels, which partly could be explained by ongoing treatment with neuroleptics and antidepressives. Previous findings of higher insulin levels in Alzheimer's disease could not be verified. PMID:8503259

  11. Mitochondrial inhibitor as a new class of insulin sensitizer.

    Science.gov (United States)

    Zhang, Yong; Ye, Jianping

    2012-08-01

    Insulin resistance is a major risk factor for type 2 diabetes. AMP-activated protein kinase (AMPK) is a drug target in the improvement of insulin sensitivity. Several insulin-sensitizing medicines are able to activate AMPK through inhibition of mitochondrial functions. These drugs, such as metformin and STZ, inhibit ATP synthesis in mitochondria to raise AMP/ATP ratio in the process of AMPK activation. However, chemicals that activate AMPK directly or by activating its upstream kinases have not been approved for treatment of type 2 diabetes in humans. In an early study, we reported that berberine inhibited oxygen consumption in mitochondria, and increased AMP/ATP ratio in cells. The observation suggests an indirect mechanism for AMPK activation by berberine. Berberine stimulates glycolysis for ATP production that offsets the cell toxicity after mitochondria inhibition. The study suggests that mitochondrial inhibition is an approach for AMPK activation. In this review article, literature is critically reviewed to interpret the role of mitochondria function in the mechanism of insulin resistance, which supports that mitochondria inhibitors represent a new class of AMPK activator. The inhibitors are promising candidates for insulin sensitizers. This review provides a guideline in search for small molecule AMPK activators in the drug discovery for type 2 diabetes. PMID:23710432

  12. Insulin-Sensitizers, Polycystic Ovary Syndrome and Gynaecological Cancer Risk

    Directory of Open Access Journals (Sweden)

    Rosa Lauretta

    2016-01-01

    Full Text Available Preclinical, early phase clinical trials and epidemiological evidence support the potential role of insulin-sensitizers in cancer prevention and treatment. Insulin-sensitizers improve the metabolic and hormonal profile in PCOS patients and may also act as anticancer agents, especially in cancers associated with hyperinsulinemia and oestrogen dependent cancers. Several lines of evidence support the protection against cancer exerted by dietary inositol, in particular inositol hexaphosphate. Metformin, thiazolidinediones, and myoinositol postreceptor signaling may exhibit direct inhibitory effects on cancer cell growth. AMPK, the main molecular target of metformin, is emerging as a target for cancer prevention and treatment. PCOS may be correlated to an increased risk for developing ovarian and endometrial cancer (up to threefold. Several studies have demonstrated an increase in mortality rate from ovarian cancer among overweight/obese PCOS women compared with normal weight women. Long-term use of metformin has been associated with lower rates of ovarian cancer. Considering the evidence supporting a higher risk of gynaecological cancer in PCOS women, we discuss the potential use of insulin-sensitizers as a potential tool for chemoprevention, hypothesizing a possible rationale through which insulin-sensitizers may inhibit tumourigenesis.

  13. Insulin-Sensitizers, Polycystic Ovary Syndrome and Gynaecological Cancer Risk

    Science.gov (United States)

    Lauretta, Rosa; Lanzolla, Giulia; Vici, Patrizia; Mariani, Luciano; Moretti, Costanzo

    2016-01-01

    Preclinical, early phase clinical trials and epidemiological evidence support the potential role of insulin-sensitizers in cancer prevention and treatment. Insulin-sensitizers improve the metabolic and hormonal profile in PCOS patients and may also act as anticancer agents, especially in cancers associated with hyperinsulinemia and oestrogen dependent cancers. Several lines of evidence support the protection against cancer exerted by dietary inositol, in particular inositol hexaphosphate. Metformin, thiazolidinediones, and myoinositol postreceptor signaling may exhibit direct inhibitory effects on cancer cell growth. AMPK, the main molecular target of metformin, is emerging as a target for cancer prevention and treatment. PCOS may be correlated to an increased risk for developing ovarian and endometrial cancer (up to threefold). Several studies have demonstrated an increase in mortality rate from ovarian cancer among overweight/obese PCOS women compared with normal weight women. Long-term use of metformin has been associated with lower rates of ovarian cancer. Considering the evidence supporting a higher risk of gynaecological cancer in PCOS women, we discuss the potential use of insulin-sensitizers as a potential tool for chemoprevention, hypothesizing a possible rationale through which insulin-sensitizers may inhibit tumourigenesis. PMID:27725832

  14. Insulin sensitivity and metabolic flexibility following exercise training among different obese insulin-resistant phenotypes.

    Science.gov (United States)

    Malin, Steven K; Haus, Jacob M; Solomon, Thomas P J; Blaszczak, Alecia; Kashyap, Sangeeta R; Kirwan, John P

    2013-11-15

    Impaired fasting glucose (IFG) blunts the reversal of impaired glucose tolerance (IGT) after exercise training. Metabolic inflexibility has been implicated in the etiology of insulin resistance; however, the efficacy of exercise on peripheral and hepatic insulin sensitivity or substrate utilization in adults with IFG, IGT, or IFG + IGT is unknown. Twenty-four older (66.7 ± 0.8 yr) obese (34.2 ± 0.9 kg/m(2)) adults were categorized as IFG (n = 8), IGT (n = 8), or IFG + IGT (n = 8) according to a 75-g oral glucose tolerance test (OGTT). Subjects underwent 12-wk of exercise (60 min/day for 5 days/wk at ∼85% HRmax) and were instructed to maintain a eucaloric diet. A euglycemic hyperinsulinemic clamp (40 mU·m(2)·min(-1)) with [6,6-(2)H]glucose was used to determine peripheral and hepatic insulin sensitivity. Nonoxidative glucose disposal and metabolic flexibility [insulin-stimulated respiratory quotient (RQ) minus fasting RQ] were also assessed. Glucose incremental area under the curve (iAUCOGTT) was calculated from the OGTT. Exercise increased clamp-derived peripheral and hepatic insulin sensitivity more in adults with IFG or IGT alone than with IFG + IGT (P metabolic flexibility, reduced fasting RQ, and higher nonoxidative glucose disposal (P metabolic flexibility, which was related to blunted improvements in postprandial glucose. Additional work is required to assess the molecular mechanism(s) by which chronic hyperglycemia modifies insulin sensitivity following exercise training. PMID:24064339

  15. Does bicarbonated mineral water rich in sodium change insulin sensitivity of postmenopausal women? ¿Modifica el agua mineral bicarbonatada rica en sodio la sensibilidad a la insulina de las mujeres postmenopáusicas?

    Directory of Open Access Journals (Sweden)

    S. Schoppen

    2007-10-01

    Full Text Available Aim: To study the effects of drinking 0.5 L of two sodium-rich bicarbonated mineral waters (BMW-1 and 2, with a standard meal, on postprandial insulin and glucose changes. And to determine, if the effects vary depending on insulin resistance, measured by homeostasis model assessment (HOMA. Methods: In a 3-way randomized crossover study, 18 healthy postmenopausal women consumed two sodiumrich BMWs and a low-mineral water (LMW with a standard fat-rich meal. Fasting and postprandial blood samples were taken at 30, 60 and 120 min. Serum glucose, insulin, cholesterol and triacylglycerols were determined. Insulin resistance was estimated by HOMA and insulin sensitivity was calculated by quantitative insulin sensitivity check index (QUICKY. Results: Glucose levels did not change. HOMA and QUICKY values were highly inversely correlated (r = -1,000; p Objetivo: Estudiar los efectos de la ingesta de 0.5L de dos aguas minerales bicarbonatadas ricas en sodio (BMW-1 y 2, junto con una comida estándar, sobre los cambios en la insulina y la glucosa postprandial; y determinar si los posibles efectos varían en función de la resistencia a la insulina evaluada a través del modelo homeostático (HOMA. Métodos: 18 mujeres postmenopáusicas sanas participaron en un estudio triple cruzado aleatorizado, en el que bebieron 2 aguas minerales bicarbonatadas ricas en sodio (BMW-1 y 2 y un agua mineral débil (LMW junto con una comida estándar rica en grasa. Se tomaron muestras de sangre en ayunas y postprandiales a los 30, 60 y 120 min. Se determinó glucosa, insulina, colesterol y triglicéridos en suero. La resistencia a la insulina fue estimada a través del HOMA y la sensibilidad a la insulina se calculó mediante el índice de sensibilidad cuantitativa a la insulina (QUICKY. Resultados: Los niveles de glucosa no presentaron cambios. Los valores de HOMA y QUICKY presentaron una fuerte correlación inversa (r = -1,000; p < 0,0001. Las concentraciones de insulina

  16. Insulin sensitizers in treatment of nonalcoholic fatty liver disease: Systematic review

    Institute of Scientific and Technical Information of China (English)

    Norberto C Chavez-Tapia; Tonatiuh Barrientos-Gutierrez; Felix I Tellez-(A)vila; Francisco Sánchez-(A)vila; Maria Antonieta Monta(n)o-Reyes; Misael Uribe

    2006-01-01

    AIM: To summarize the evidence available for the clinical effectiveness of insulin sensitizers in the treatment of nonalcoholic fatty liver disease (NAFLD) systematically.METHODS: Relevant articles were located using computer-assisted searches of Medline (1966-March 2006), EMBASE (1988-March 2006), CINAHL (1982-March 2003), Educational Resource Information Center (1966-March 2006), Library, Information Science & Technology Abstracts(1967-March 2006), Cochrane Database of Systematic Reviews, Database of Abstractsof Reviews of Effects (1994-2006), dissertations in ProQuest and FirstSearch databases. Manual searches were made in the Abstractsfrom meetings of the American Gastroenterological Association (1999-2006),and the American Association for the Study of Liver Diseases (2003-2005). Studies were retrieved using the following selection criteria: (1) clinical trials using insulin sensitizers in subjects with NAFLD, (2) adult patients, (3) published as full manuscripts or Abstracts and (4) English, Spanish, German, and French languages only. Data were Abstracts independently by two reviewers following standardized procedures. A face-toface comparison of data was conducted to ensure the completeness and reliability of the Abstracts process.RESULTS: Nine studies were included, six using metformin and three using thiazolidinediones. Only two studies were placebo-controlled trials. The median sample size for all studies was 18 subjects. In the placebo-controlled trials, metformin improved insulin resistance markers and liver function tests, but not histological scores. In the single-arm trials, metformin and thiazolidinediones improved insulin resistance markers and liver function tests, and beneficial histological changes were reported. There is limited high-quality information available from which to draw categorical conclusions about the clinical use of insulin sensitizers in NAFLD.CONCLUSION: Current information indicates that the use of insulin sensitizers in NAFLD

  17. Effects of Dietary n-3 Fatty Acids on Hepatic and Peripheral Insulin Sensitivity in Insulin-Resistant Humans

    OpenAIRE

    Lalia, Antigoni Z; Johnson, Matthew L; Jensen, Michael D.; Hames, Kazanna C.; Port, John D.; Lanza, Ian R.

    2015-01-01

    OBJECTIVE Dietary n-3 polyunsaturated fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), prevent insulin resistance and stimulate mitochondrial biogenesis in rodents, but the findings of translational studies in humans are thus far ambiguous. The aim of this study was to evaluate the influence of EPA and DHA on insulin sensitivity, insulin secretion, and muscle mitochondrial function in insulin-resistant, nondiabetic humans using a robust study design and gold-...

  18. Environmental factors and dam characteristics associated with insulin sensitivity and insulin secretion in newborn Holstein calves.

    Science.gov (United States)

    Kamal, M M; Van Eetvelde, M; Bogaert, H; Hostens, M; Vandaele, L; Shamsuddin, M; Opsomer, G

    2015-09-01

    The objective of the present retrospective cohort study was to evaluate potential associations between environmental factors and dam characteristics, including level of milk production during gestation, and insulin traits in newborn Holstein calves. Birth weight and gestational age of the calves at delivery were determined. On the next day, heart girth, wither height and diagonal length of both the calves and their dams were measured. Parity, body condition score and age at calving were recorded for all dams. For the cows, days open before last gestation, lactation length (LL), length of dry period (DP) and calving interval were also calculated. The magnitude and shape of the lactation curve both quantified using the MilkBot model based on monthly milk weights, were used to calculate the amount of milk produced during gestation. Using the same procedure, cumulative milk production from conception to drying off (MGEST) was calculated. A blood sample was collected from all calves (n=481; 169 born to heifers and 312 born to cows) at least 5 h after a milk meal on day 3 of life to measure basal glucose and insulin levels. In addition, an intravenous glucose-stimulated insulin secretion test was performed in a subset of the calves (n=316). After descriptive analysis, generalized linear mixed models were used to identify factors that were significantly associated with the major insulin traits (Insb, basal insulin level; QUICKI, quantitative insulin sensitivity check index; AIR, acute insulin response; DI, disposition index) of the newborn calves. The overall average birth weight of the calves was 42.7 ± 5.92 kg. The insulin traits were significantly associated with gender and season of birth when data of all calves were analyzed. In addition, the insulin traits in calves born to cows were significantly associated with MGEST, DP and LL. The Insb was estimated to be higher in calves born to the cows having passed a higher MGEST (P=0.076) and longer DP (P=0.034). The

  19. Modulation of age-related insulin sensitivity by VEGF-dependent vascular plasticity in adipose tissues.

    Science.gov (United States)

    Honek, Jennifer; Seki, Takahiro; Iwamoto, Hideki; Fischer, Carina; Li, Jingrong; Lim, Sharon; Samani, Nilesh J; Zang, Jingwu; Cao, Yihai

    2014-10-14

    Mechanisms underlying age-related obesity and insulin resistance are generally unknown. Here, we report age-related adipose vascular changes markedly modulated fat mass, adipocyte functions, blood lipid composition, and insulin sensitivity. Notably, VEGF expression levels in various white adipose tissues (WATs) underwent changes uninterruptedly in different age populations. Anti-VEGF and anti- VEGF receptor 2 treatment in different age populations showed marked variations of vascular regression, with midaged mice exhibiting modest sensitivity. Interestingly, anti-VEGF treatment produced opposing effects on WAT adipocyte sizes in different age populations and affected vascular density and adipocyte sizes in brown adipose tissue. Consistent with changes of vasculatures and adipocyte sizes, anti-VEGF treatment increased insulin sensitivity in young and old mice but had no effects in the midaged group. Surprisingly, anti-VEGF treatment significantly improved insulin sensitivity in midaged obese mice fed a high-fat diet. Our findings demonstrate that adipose vasculatures show differential responses to anti-VEGF treatment in various age populations and have therapeutic implications for treatment of obesity and diabetes with anti-VEGF-based antiangiogenic drugs.

  20. Proximity to Delivery Alters Insulin Sensitivity and Glucose Metabolism in Pregnant Mice.

    Science.gov (United States)

    Musial, Barbara; Fernandez-Twinn, Denise S; Vaughan, Owen R; Ozanne, Susan E; Voshol, Peter; Sferruzzi-Perri, Amanda N; Fowden, Abigail L

    2016-04-01

    In late pregnancy, maternal insulin resistance occurs to support fetal growth, but little is known about insulin-glucose dynamics close to delivery. This study measured insulin sensitivity in mice in late pregnancy at day 16 (D16) and near term at D19. Nonpregnant (NP) and pregnant mice were assessed for metabolite and hormone concentrations, body composition by DEXA, tissue insulin signaling protein abundance by Western blotting, glucose tolerance and utilization, and insulin sensitivity using acute insulin administration and hyperinsulinemic-euglycemic clamps with [(3)H]glucose infusion. Whole-body insulin resistance occurred in D16 pregnant dams in association with basal hyperinsulinemia, insulin-resistant endogenous glucose production, and downregulation of several proteins in hepatic and skeletal muscle insulin signaling pathways relative to NP and D19 values. Insulin resistance was less pronounced at D19, with restoration of NP insulin concentrations, improved hepatic insulin sensitivity, and increased abundance of hepatic insulin signaling proteins. At D16, insulin resistance at whole-body, tissue, and molecular levels will favor fetal glucose acquisition, while improved D19 hepatic insulin sensitivity will conserve glucose for maternal use in anticipation of lactation. Tissue sensitivity to insulin, therefore, alters differentially with proximity to delivery in pregnant mice, with implications for human and other species. PMID:26740602

  1. Cattle temperament influences metabolism: metabolic response to glucose tolerance and insulin sensitivity tests in beef steers.

    Science.gov (United States)

    Burdick Sanchez, N C; Carroll, J A; Broadway, P R; Hughes, H D; Roberts, S L; Richeson, J T; Schmidt, T B; Vann, R C

    2016-07-01

    Cattle temperament, defined as the reactivity of cattle to humans or novel environments, can greatly influence several physiological systems in the body, including immunity, stress, and most recently discovered, metabolism. Greater circulating concentrations of nonesterified fatty acids (NEFAs) found in temperamental cattle suggest that temperamental cattle are metabolically different than calm cattle. Further, elevated NEFA concentrations have been reported to influence insulin sensitivity. Therefore, the objective of this study was to determine whether cattle temperament would influence the metabolic response to a glucose tolerance test (GTT) and insulin sensitivity test (IST). Angus-cross steers (16 calm and 15 temperamental; 216 ± 6 kg BW) were selected based on temperament score measured at weaning. On day 1, steers were moved into indoor stanchions to allow measurement of individual ad libitum feed intake. On day 6, steers were fitted with indwelling rectal temperature probes and jugular catheters. At 9 AM on day 7, steers received the GTT (0.5-mL/kg BW of a 50% dextrose solution), and at 2 PM on day 7, steers received the IST (2.5 IU bovine insulin/kg BW). Blood samples were collected and serum isolated at -60, -45, -30, -15, 0, 10, 20, 30, 45, 60, 90, 120, and 150 min relative to each challenge. Serum was stored at -80°C until analyzed for cortisol, glucose, NEFA, and blood urea nitrogen concentrations. All variables changed over time (P < 0.01). For the duration of the study, temperamental steers maintained greater (P < 0.01) serum NEFA and less (P ≤ 0.01) serum blood urea nitrogen and insulin sensitivity (calculated using Revised Quantitative Insulin Sensitivity Check Index) compared with calm steers. During the GTT, temperamental steers had greater (P < 0.01) serum glucose, yet decreased (P = 0.03) serum insulin and (P < 0.01) serum insulin: serum glucose compared to calm cattle. During the IST, temperamental steers had greater (P < 0.01) serum

  2. The effects of acute exercise on serum adiponectin and resistin levels and their relation to insulin sensitivity in overweight males.

    Science.gov (United States)

    Jamurtas, A Z; Theocharis, V; Koukoulis, G; Stakias, N; Fatouros, I G; Kouretas, D; Koutedakis, Y

    2006-05-01

    The purpose of this study was to investigate the effects of a submaximal aerobic exercise bout on adiponectin and resistin levels as well as insulin sensitivity, until 48 h post-exercise in healthy overweight males. Nine subjects performed an exercise bout at an intensity corresponding to approximately 65% of their maximal oxygen consumption for 45 min. Adiponectin, resistin, cortisol, insulin, glucose and insulin sensitivity were measured prior to exercise, immediately after exercise as well as 24 and 48 h after exercise. Data were analyzed using repeated measures ANOVA while Pearson's correlations were performed to identify possible relationship among the assessed variables. There were no significant differences for adiponectin (microg ml(-1)) [pre, 3.61(0.73); post, 3.15(0.43); 24 h, 3.15(0.81); 48 h, 3.37(0.76)] or resistin (ng ml(-1)) [pre, 0.19(0.03); post, 0.13(0.03); 24 h, 0.23(0.04); 48 h, 0.23(0.03)] across time. Insulin sensitivity increased and insulin concentration decreased significantly only immediately after exercise. Furthermore, no significant correlations were observed among the variables assessed except for the expected between insulin level and insulin sensitivity. These results indicate that a submaximal aerobic workout does not result in significant changes in adiponectin and resistin up to 48 h post-exercise. Furthermore, it appears that adiponectin or resistin is not associated with insulin sensitivity. PMID:16525810

  3. Resistance training, insulin sensitivity and muscle function in the elderly

    DEFF Research Database (Denmark)

    Dela, Flemming; Kjaer, Michael

    2006-01-01

    Ageing is associated with a loss in both muscle mass and in the metabolic quality of skeletal muscle. This leads to sarcopenia and reduced daily function, as well as to an increased risk for development of insulin resistance and type 2 diabetes. A major part, but not all, of these changes...

  4. The impact of pegvisomant treatment on substrate metabolism and insulin sensitivity in patients with acromegaly

    DEFF Research Database (Denmark)

    Lindberg-Larsen, Rune; Møller, Niels; Schmitz, Ole;

    2007-01-01

    CONTEXT: Pegvisomant is a specific GH receptor antagonist that is able to normalize serum IGF-I concentrations in most patients with acromegaly. The impact of pegvisomant on insulin sensitivity and substrate metabolism is less well described. PATIENTS AND METHODS: We assessed basal and insulin......-stimulated (euglycemic clamp) substrate metabolism in seven patients with active acromegaly before and after 4-wk pegvisomant treatment (15 mg/d) in an open design. RESULTS: After pegvisomant, IGF-I decreased, whereas GH increased (IGF-I, 621 +/- 82 vs. 247 +/- 33 microg/liter, P = 0.02; GH, 5.3 +/- 1.5 vs. 10.8 +/- 3...... vs. 1563 +/- 101 kcal/24 h, P = 0.03), but the rate of lipid oxidation did not change significantly. CONCLUSIONS: 1) Pegvisomant treatment for 4 wk improves peripheral and hepatic insulin sensitivity in acromegaly. 2) This is associated with a decrease in resting energy expenditure, whereas free...

  5. Effect of training on insulin sensitivity of glucose uptake and lipolysis in human adipose tissue

    DEFF Research Database (Denmark)

    Stallknecht, Bente; Larsen, J J; Mikines, K J;

    2000-01-01

    Training increases insulin sensitivity of both whole body and muscle in humans. To investigate whether training also increases insulin sensitivity of adipose tissue, we performed a three-step hyperinsulinemic, euglycemic clamp in eight endurance-trained (T) and eight sedentary (S) young men...... [insulin infusion rates: 10,000 (step I), 20,000 (step II), and 150,000 (step III) microU x min(-1) x m(-2)]. Glucose and glycerol concentrations were measured in arterial blood and also by microdialysis in interstitial fluid in periumbilical, subcutaneous adipose tissue and in quadriceps femoris muscle...... (glucose only). Adipose tissue blood flow was measured by (133)Xe washout. In the basal state, adipose tissue blood flow tended to be higher in T compared with S subjects, and in both groups blood flow was constant during the clamp. The change from basal in arterial-interstitial glucose concentration...

  6. Brown adipose tissue regulates glucose homeostasis and insulin sensitivity

    OpenAIRE

    Stanford, Kristin I.; Middelbeek, Roeland J.W.; Townsend, Kristy L.; An, Ding; Nygaard, Eva B.; Hitchcox, Kristen M.; Markan, Kathleen R.; Nakano, Kazuhiro; Hirshman, Michael F.; Tseng, Yu-Hua; Goodyear, Laurie J.

    2012-01-01

    Brown adipose tissue (BAT) is known to function in the dissipation of chemical energy in response to cold or excess feeding, and also has the capacity to modulate energy balance. To test the hypothesis that BAT is fundamental to the regulation of glucose homeostasis, we transplanted BAT from male donor mice into the visceral cavity of age- and sex-matched recipient mice. By 8–12 weeks following transplantation, recipient mice had improved glucose tolerance, increased insulin sensitivity, lowe...

  7. The Effect of Acute Exercise on Serum Vaspin Level and Its Relation to Insulin Sensitivity in Overweight Elderly Men

    Directory of Open Access Journals (Sweden)

    Jabbar Bashiri

    2014-08-01

    Full Text Available Background: Vaspin is a new discovered adipocytokine which is a member of serine protease inhibitor family secreted from adipose tissue and might play a role in insulin sensitivity. The purpose of this study was to investigate the effect of acute exercise on serum vaspin levels and its relation to insulin sensitivity in overweight elderly men. Materials and Methods: In this semi-experimental study, 12 healthy elderly men volunteers randomly selected and performed one session aerobic exercise including 30 minutes of cycling at 70-75% of HRmax, which was followed by 30 minutes of recovery. Three blood samples were taken before exercise, immediately after exercise and after 30 minutes of recovery. Data were analyzed by repeated measure ANOVA and Bonferroni test and Pearson’s correlations were performed to identify possible relationship among the assessed variables. Statistical significance was set at p≤0.05. Results: There were no significant differences for vaspin across time. Insulin and glucose concentration and insulin resistance decreased immediately after exercise. However insulin concentration and insulin resistance returned to pre-exercise level at the end of recovery. Furthermore, no significant correlations were observed among the variables assessed except for the expected between insulin level and insulin resistance. Conclusion: These results indicate that a sub-maximal aerobic workout does not result in significant changes in vaspin levels in elderly men. Furthermore, we observed that vaspin is not associated with insulin sensitivity in this study.

  8. Heart Rate Variability, Insulin Resistance, and Insulin Sensitivity in Japanese Adults: The Toon Health Study

    Directory of Open Access Journals (Sweden)

    Isao Saito

    2015-09-01

    Full Text Available Background: Although impaired cardiac autonomic function is associated with an increased risk of type 2 diabetes in Caucasians, evidence in Asian populations with a lower body mass index is limited. Methods: Between 2009–2012, the Toon Health Study recruited 1899 individuals aged 30–79 years who were not taking medication for diabetes. A 75-g oral glucose tolerance test was used to diagnose type 2 diabetes, and fasting and 2-h-postload glucose and insulin concentrations were measured. We assessed the homeostasis model assessment index for insulin resistance (HOMA-IR and Gutt’s insulin sensitivity index (ISI. Pulse was recorded for 5 min, and time-domain heart rate variability (HRV indices were calculated: the standard deviation of normal-to-normal intervals (SDNN and the root mean square of successive difference (RMSSD. Power spectral analysis provided frequency domain measures of HRV: high frequency (HF power, low frequency (LF power, and the LF:HF ratio. Results: Multivariate-adjusted logistic regression models showed decreased SDNN, RMSSD, and HF, and increased LF:HF ratio were associated significantly with increased HOMA-IR and decreased ISI. When stratified by overweight status, the association of RMSSD, HF, and LF:HF ratio with decreased ISI was also apparent in non-overweight individuals. The interaction between LF:HF ratio and decreased ISI in overweight individuals was significant, with the odds ratio for decreased ISI in the highest quartile of LF:HF ratio in non-overweight individuals being 2.09 (95% confidence interval, 1.41–3.10. Conclusions: Reduced HRV was associated with insulin resistance and lower insulin sensitivity. Decreased ISI was linked with parasympathetic dysfunction, primarily in non-overweight individuals.

  9. New measure of insulin sensitivity predicts cardiovascular disease better than HOMA estimated insulin resistance.

    Directory of Open Access Journals (Sweden)

    Kavita Venkataraman

    Full Text Available CONTEXT: Accurate assessment of insulin sensitivity may better identify individuals at increased risk of cardio-metabolic diseases. OBJECTIVES: To examine whether a combination of anthropometric, biochemical and imaging measures can better estimate insulin sensitivity index (ISI and provide improved prediction of cardio-metabolic risk, in comparison to HOMA-IR. DESIGN AND PARTICIPANTS: Healthy male volunteers (96 Chinese, 80 Malay, 77 Indian, 21 to 40 years, body mass index 18-30 kg/m(2. Predicted ISI (ISI-cal was generated using 45 randomly selected Chinese through stepwise multiple linear regression, and validated in the rest using non-parametric correlation (Kendall's tau τ. In an independent longitudinal cohort, ISI-cal and HOMA-IR were compared for prediction of diabetes and cardiovascular disease (CVD, using ROC curves. SETTING: The study was conducted in a university academic medical centre. OUTCOME MEASURES: ISI measured by hyperinsulinemic euglycemic glucose clamp, along with anthropometric measurements, biochemical assessment and imaging; incident diabetes and CVD. RESULTS: A combination of fasting insulin, serum triglycerides and waist-to-hip ratio (WHR provided the best estimate of clamp-derived ISI (adjusted R(2 0.58 versus 0.32 HOMA-IR. In an independent cohort, ROC areas under the curve were 0.77±0.02 ISI-cal versus 0.76±0.02 HOMA-IR (p>0.05 for incident diabetes, and 0.74±0.03 ISI-cal versus 0.61±0.03 HOMA-IR (p<0.001 for incident CVD. ISI-cal also had greater sensitivity than defined metabolic syndrome in predicting CVD, with a four-fold increase in the risk of CVD independent of metabolic syndrome. CONCLUSIONS: Triglycerides and WHR, combined with fasting insulin levels, provide a better estimate of current insulin resistance state and improved identification of individuals with future risk of CVD, compared to HOMA-IR. This may be useful for estimating insulin sensitivity and cardio-metabolic risk in clinical and

  10. APPL1 Potentiates Insulin Sensitivity by Facilitating the Binding of IRS1/2 to the Insulin Receptor

    Directory of Open Access Journals (Sweden)

    Jiyoon Ryu

    2014-05-01

    Full Text Available Binding of insulin receptor substrate proteins 1 and 2 (IRS1/2 to the insulin receptor (IR is essential for the regulation of insulin sensitivity and energy homeostasis. However, the mechanism of IRS1/2 recruitment to the IR remains elusive. Here, we identify adaptor protein APPL1 as a critical molecule that promotes IRS1/2-IR interaction. APPL1 forms a complex with IRS1/2 under basal conditions, and this complex is then recruited to the IR in response to insulin or adiponectin stimulation. The interaction between APPL1 and IR depends on insulin- or adiponectin-stimulated APPL1 phosphorylation, which is greatly reduced in insulin target tissues in obese mice. appl1 deletion in mice consistently leads to systemic insulin resistance and a significant reduction in insulin-stimulated IRS1/2, but not IR, tyrosine phosphorylation, indicating that APPL1 sensitizes insulin signaling by acting at a site downstream of the IR. Our study uncovers a mechanism regulating insulin signaling and crosstalk between the insulin and adiponectin pathways.

  11. Monomeric tartrate resistant acid phosphatase induces insulin sensitive obesity.

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    Pernilla Lång

    Full Text Available BACKGROUND: Obesity is associated with macrophage infiltration of adipose tissue, which may link adipose inflammation to insulin resistance. However, the impact of inflammatory cells in the pathophysiology of obesity remains unclear. Tartrate resistant acid phosphatase (TRAP is an enzyme expressed by subsets of macrophages and osteoclasts that exists either as an enzymatically inactive monomer or as an active, proteolytically processed dimer. PRINCIPAL FINDINGS: Using mice over expressing TRAP, we show that over-expression of monomeric, but not the dimeric form in adipose tissue leads to early onset spontaneous hyperplastic obesity i.e. many small fat cells. In vitro, recombinant monomeric, but not proteolytically processed TRAP induced proliferation and differentiation of mouse and human adipocyte precursor cells. In humans, monomeric TRAP was highly expressed in the adipose tissue of obese individuals. In both the mouse model and in the obese humans the source of TRAP in adipose tissue was macrophages. In addition, the obese TRAP over expressing mice exhibited signs of a low-grade inflammatory reaction in adipose tissue without evidence of abnormal adipocyte lipolysis, lipogenesis or insulin sensitivity. CONCLUSION: Monomeric TRAP, most likely secreted from adipose tissue macrophages, induces hyperplastic obesity with normal adipocyte lipid metabolism and insulin sensitivity.

  12. A Synergistic, Balanced Antioxidant Cocktail, Protects Aging Rats from Insulin Resistance and Absence of Meal-Induced Insulin Sensitization (AMIS Syndrome

    Directory of Open Access Journals (Sweden)

    Hui Helen Wang

    2015-01-01

    Full Text Available A series of in vivo and in vitro studies using animal and human models in the past 15 years have demonstrated that approximately 55% (~66% in humans of the glucose disposal effect of an i.v. injection of insulin in the fed state is dependent on the action of a second hormone, hepatic insulin sensitizing substance (HISS, which is released from the liver and stimulates glucose uptake in muscle, heart and kidneys. Sensitization of the insulin response by a meal through release of HISS is called meal-induced insulin sensitization (MIS. Absence of HISS action results in postprandial hyperglycemia, hyperinsulinemia, hyperlipidemia, adiposity, increased free radical stress and a cluster of progressive metabolic and cardiovascular dysfunctions referred to as the AMIS (absence of meal-induced insulin sensitization syndrome. Reduced HISS release accounts for the insulin resistance that occurs with aging and is made worse by physical inactivity and diets high in sucrose or fat. This brief review provides an update of major metabolic disturbances associated with aging due to reduction of HISS release, and the protection against these pathological changes in aging animals using a balanced synergistic antioxidant cocktail SAMEC (S-adenosylmethionine, vitamins E and C. The synergy amongst the components is consistent with the known benefits of antioxidants supplied by a mixed diet and acting through diverse mechanisms. Using only three constituents, SAMEC appears suitable as an antioxidant specifically targeting the AMIS syndrome.

  13. Sustained Self-Regulation of Energy Intake: Initial Hunger Improves Insulin Sensitivity

    Directory of Open Access Journals (Sweden)

    Mario Ciampolini

    2010-01-01

    Results. In trained subjects, significant decreases were found in insulin sensitivity index, insulin and BG peaks, glycated haemoglobin, mean pre-meal BG, standard deviation of diary BG (BG as recorded by subjects' 7-day diary, energy intake, BMI, and body weight when compared to control subjects. Conclusion. The IHMP improved insulin sensitivity and other cardiovascular risk factors over a 5-month period.

  14. Adiponectin Decreases Plasma Glucose and Improves Insulin Sensitivity in Diabetic Swine

    Institute of Scientific and Technical Information of China (English)

    Xiaobo HU; Meihua SHE; Hongjie HOU; Qinkai LI; Qingyun SHEN; Yi LUO; Weidong YIN

    2007-01-01

    To investigate the effects of recombinant human adiponectin on the metabolism of diabetic swine induced by feeding a high-fat/high-sucrose diet (HFSD), diabetic animal models were constructed by feeding swine with HFSD for 6 months. The effects of recombinant adiponectin were assessed by detecting the change of plasma glucose levels by commercially available enzymatic method test kits and evaluating the insulin sensitivity by oral glucose tolerance test (OGTT). About 1.5 g purified recombinant adiponectin was produced using a 15-liter fermenter. A single injection of purified recombinant human adiponectin to diabetic swine led to a 2- to 3-fold elevation in circulating adiponectin, which triggered a transient decrease in basal glucose level (P<0.05). This effect on glucose was not associated with an increase in insulin level. Moreover, after adiponectin injection, swine also showed improved insulin sensitivity compared with the control (P<0.05). Adiponectin might have the potential to be a glucose-lowering agent for metabolic disease. Adiponectin as a potent insulin enhancer linking adipose tissue and glucose metabolism could be useful to treat insulin resistance.

  15. Genome-wide association study of the modified Stumvoll Insulin Sensitivity Index identifies BCL2 and FAM19A2 as novel insulin sensitivity loci

    DEFF Research Database (Denmark)

    Walford, Geoffrey A; Gustafsson, Stefan; Rybin, Denis;

    2016-01-01

    Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed GWAS of the...

  16. Changes in Gastrointestinal Hormone Responses, Insulin Sensitivity, and Beta-Cell Function Within 2 Weeks After Gastric Bypass in Non-diabetic Subjects

    DEFF Research Database (Denmark)

    Jacobsen, S H; Olesen, S C; Dirksen, C;

    2012-01-01

    Roux-en-Y gastric bypass (RYGB) surgery causes profound changes in secretion of gastrointestinal hormones and glucose metabolism. We present a detailed analysis of the early hormone changes after RYGB in response to three different oral test meals designed to provide this information without...

  17. Short-Term Exercise Training Improves Insulin Sensitivity but Does Not Inhibit Inflammatory Pathways in Immune Cells from Insulin-Resistant Subjects

    Directory of Open Access Journals (Sweden)

    Sara M. Reyna

    2013-01-01

    Full Text Available Background. Exercise has an anti-inflammatory effect against, and immune cells play critical roles in the development, of insulin resistance and atherosclerotic vascular disease (AVD. Thus, the goal of this study was to determine whether exercise improves insulin sensitivity in insulin-resistant subjects by downregulating proinflammatory signaling in immune cells. Methods. Seventeen lean, 8 obese nondiabetic, and 11 obese type 2 diabetic individuals underwent an aerobic exercise program for 15 days and an insulin clamp before and after exercise. Peripheral mononuclear cells (PMNC were obtained for determination of Toll-like receptor (TLR 2 and 4 protein content and mitogen-activated protein kinase phosphorylation. Results. Compared with that in lean individuals, TLR4 protein content was increased by 4.2-fold in diabetic subjects. This increase in TLR4 content was accompanied by a 3.0-fold increase in extracellular signal-regulated kinase (ERK phosphorylation. Exercise improved insulin sensitivity in the lean, obese, and type 2 diabetes groups. However, exercise did not affect TLR content or ERK phosphorylation. Conclusions. TLR4 content and ERK phosphorylation are increased in PMNC of type 2 diabetic individuals. While exercise improves insulin sensitivity, this effect is not related to changes in TLR2/TLR4 content or ERK phosphorylation in PMNC of type 2 diabetic individuals.

  18. The effect of 30 months of low-dose replacement therapy with recombinant human growth hormone (rhGH) on insulin and C-peptide kinetics, insulin secretion, insulin sensitivity, glucose effectiveness, and body composition in GH-deficient adults

    DEFF Research Database (Denmark)

    Rosenfalck, A M; Maghsoudi, S; Fisker, S;

    2000-01-01

    (frequently sampled iv glucose tolerance test) glucose tolerance test, and body composition was estimated by dual-energy x-ray absorptiometry. Treatment with rhGH induced persistent favorable changes in body composition, with a 10% increase in lean body mass (P ....002); however, the glucose tolerance deteriorated significantly, and three patients developed impaired glucose tolerance. Fasting insulin level (P score increased significantly, indicating a deterioration in insulin sensitivity; whereas...

  19. Changing the insulin receptor to possess insulin-like growth factor I ligand specificity

    International Nuclear Information System (INIS)

    To examine the role of the N-terminal part of the insulin-like growth factor I (IGF-I) receptor and insulin receptor in determining ligand specificity, the authors prepared an expression vector encoding a hybrid receptor where exon 1 (encoding the signal peptide and seven amino acids of the α-subunit), exon 2, and exon 3 of the insulin receptor were replaced with the corresponding IGF-I receptor cDNA (938 nucleotides). To allow direct quantitative comparison of the binding capabilities of this hybrid receptor with those of the human IGF-I receptor and the insulin receptor, all three receptors were expressed in baby hamster kidney (BHK) cells as soluble molecules and partially purified before characterization. The hybrid IGF-I/insulin receptor bound IGF-I with an affinity comparable to that of the wild-type IGF-I receptor. In contrast, the hybrid receptor no longer displayed high-affinity binding of insulin. These results directly demonstrate that it is possible to change the specificity of the insulin receptor to that of the IGF-I receptor and, furthermore, that the binding specificity for IGF-I is encoded within the nucleotide sequence from 135 to 938 of the IGF-I receptor cDNA. Since the hybrid receptor only bound insulin with low affinity, the insulin binding region is likely to be located within exons 2 and 3 of the insulin receptor

  20. Changing the insulin receptor to possess insulin-like growth factor I ligand specificity

    Energy Technology Data Exchange (ETDEWEB)

    Andersen, A.S.; Kjeldsen, T.; Wiberg, F.C.; Christensen, P.M.; Rasmussen, J.S.; Norris, K.; Moeller, K.B.; Moeller, N.P.H. (Biopharmaceuticals Div., Bagsvaerd (Denmark))

    1990-08-14

    To examine the role of the N-terminal part of the insulin-like growth factor I (IGF-I) receptor and insulin receptor in determining ligand specificity, the authors prepared an expression vector encoding a hybrid receptor where exon 1 (encoding the signal peptide and seven amino acids of the {alpha}-subunit), exon 2, and exon 3 of the insulin receptor were replaced with the corresponding IGF-I receptor cDNA (938 nucleotides). To allow direct quantitative comparison of the binding capabilities of this hybrid receptor with those of the human IGF-I receptor and the insulin receptor, all three receptors were expressed in baby hamster kidney (BHK) cells as soluble molecules and partially purified before characterization. The hybrid IGF-I/insulin receptor bound IGF-I with an affinity comparable to that of the wild-type IGF-I receptor. In contrast, the hybrid receptor no longer displayed high-affinity binding of insulin. These results directly demonstrate that it is possible to change the specificity of the insulin receptor to that of the IGF-I receptor and, furthermore, that the binding specificity for IGF-I is encoded within the nucleotide sequence from 135 to 938 of the IGF-I receptor cDNA. Since the hybrid receptor only bound insulin with low affinity, the insulin binding region is likely to be located within exons 2 and 3 of the insulin receptor.

  1. A randomized trial comparing the effect of weight loss and exercise training on insulin sensitivity and glucose metabolism in coronary artery disease

    DEFF Research Database (Denmark)

    Pedersen, Lene Rørholm; Olsen, Rasmus Huan; Jürs, Anders;

    2015-01-01

    difference between the groups (pvisceral abdominal fat, waist circumference and body weight. Intention-to-treat analyses (n=64......) yielded similar results. CONCLUSION: LED is superior to AIT in improving insulin sensitivity in prediabetic CAD patients. Changes in insulin sensitivity are associated with decreased visceral abdominal fat, waist circumference and body weight....

  2. Does bicarbonated mineral water rich in sodium change insulin sensitivity of postmenopausal women? ¿Modifica el agua mineral bicarbonatada rica en sodio la sensibilidad a la insulina de las mujeres postmenopáusicas?

    OpenAIRE

    Schoppen, S.; Sánchez-Muniz, F. J.; A. M.ª Pérez-Granados; Gómez-Gerique, J.A.; Sarriá, B.; S. Navas-Carretero; M.ª Pilar Vaquero

    2007-01-01

    Aim: To study the effects of drinking 0.5 L of two sodium-rich bicarbonated mineral waters (BMW-1 and 2), with a standard meal, on postprandial insulin and glucose changes. And to determine, if the effects vary depending on insulin resistance, measured by homeostasis model assessment (HOMA). Methods: In a 3-way randomized crossover study, 18 healthy postmenopausal women consumed two sodiumrich BMWs and a low-mineral water (LMW) with a standard fat-rich meal. Fasting and postprandial blood sam...

  3. Minor long-term changes in weight have beneficial effects on insulin sensitivity and β-cell function in obese subjects

    DEFF Research Database (Denmark)

    James, W P; Hilsted, Jannik

    2001-01-01

    that with an individualized weight-management program, most obese patients can achieve metabolically significant weight loss, and this loss can be sustained in most patients who continue therapy for 2 years. New analyses reveal that those patients who maintain a higher level of physical activity do better, and the prediction......In asking that weight loss be maintained for periods greater than a few months, physicians are asking a great deal of their patients. In Western society, this means substantial behavioral change in an environment and culture that promotes weight gain. It is extremely common for people to regain...

  4. Dietary composition and its associations with insulin sensitivity and insulin secretion in youth.

    Science.gov (United States)

    Henderson, Mélanie; Benedetti, Andrea; Gray-Donald, Katherine

    2014-02-01

    The objectives of the present study were to examine the associations between macronutrient intake and insulin sensitivity (IS) and insulin secretion (ISct), taking into consideration moderate-to-vigorous physical activity (MVPA), fitness and sedentary behaviour. Caucasian youth (n 630) aged 8-10 years at recruitment, with at least one obese biological parent, were studied (QUebec Adipose and Lifestyle InvesTigation in Youth cohort). IS was measured using the homeostasis model assessment (HOMA) of insulin resistance and Matsuda IS index. ISct was measured using HOMA2%-β, the ratio of the AUC of insulin:glucose over the first 30 min (AUC I/G(t= 30 min)) of the oral glucose tolerance test and AUC I/G(t= 120 min) over 2 h. Fitness was measured using VO₂(peak), percentage of fat mass by dual-energy X-ray absorptiometry, and 7 d MVPA using accelerometry; screen time (ST) by average daily hours of self-reported television, video game or computer use. Dietary composition was measured using three non-consecutive dietary recalls. Non-parametric smoothing splines were used to model non-linear associations; all models were adjusted for age, sex, season, pubertal stage, MVPA, fitness, ST and adiposity. The percentage of total daily energy from dietary protein, fat, saturated fat and carbohydrate and the consumption of dietary vitamin D, sugar-sweetened beverages, fibre and portions of fruits and vegetables were taken into consideration. No dietary component was associated with any measure of IS after adjusting for MVPA, fitness, ST and adiposity. For every 1% increase in daily protein intake (%), AUC I/G(t= 30 min) decreased by 1·1% (P= 0·033). Otherwise, dietary composition was not associated with ISct. While long-term excess of energy intake has been shown to lead to overweight and obesity, dietary macronutrient composition is not independently correlated with IS or ISct in youth. PMID:24047611

  5. Insulin

    Science.gov (United States)

    ... Short Acting Humulin N NPH Human Insulin (Human Insulin Isophane Suspension) Intermediate Acting Novolin N NPH Human Insulin (Human Insulin Isophane Suspension) Intermediate Acting Lantus Insulin Glargine Long Acting ...

  6. Myostatin inhibition in muscle, but not adipose tissue, decreases fat mass and improves insulin sensitivity.

    Directory of Open Access Journals (Sweden)

    Tingqing Guo

    Full Text Available Myostatin (Mstn is a secreted growth factor expressed in skeletal muscle and adipose tissue that negatively regulates skeletal muscle mass. Mstn(-/- mice have a dramatic increase in muscle mass, reduction in fat mass, and resistance to diet-induced and genetic obesity. To determine how Mstn deletion causes reduced adiposity and resistance to obesity, we analyzed substrate utilization and insulin sensitivity in Mstn(-/- mice fed a standard chow. Despite reduced lipid oxidation in skeletal muscle, Mstn(-/- mice had no change in the rate of whole body lipid oxidation. In contrast, Mstn(-/- mice had increased glucose utilization and insulin sensitivity as measured by indirect calorimetry, glucose and insulin tolerance tests, and hyperinsulinemic-euglycemic clamp. To determine whether these metabolic effects were due primarily to the loss of myostatin signaling in muscle or adipose tissue, we compared two transgenic mouse lines carrying a dominant negative activin IIB receptor expressed specifically in adipocytes or skeletal muscle. We found that inhibition of myostatin signaling in adipose tissue had no effect on body composition, weight gain, or glucose and insulin tolerance in mice fed a standard diet or a high-fat diet. In contrast, inhibition of myostatin signaling in skeletal muscle, like Mstn deletion, resulted in increased lean mass, decreased fat mass, improved glucose metabolism on standard and high-fat diets, and resistance to diet-induced obesity. Our results demonstrate that Mstn(-/- mice have an increase in insulin sensitivity and glucose uptake, and that the reduction in adipose tissue mass in Mstn(-/- mice is an indirect result of metabolic changes in skeletal muscle. These data suggest that increasing muscle mass by administration of myostatin antagonists may be a promising therapeutic target for treating patients with obesity or diabetes.

  7. Fabrication of Glucose-Sensitive Layer-by-Layer Films for Potential Controlled Insulin Release Applications

    Directory of Open Access Journals (Sweden)

    Talusan Timothy Jemuel E.

    2015-01-01

    Full Text Available Self-regulated drug delivery systems (DDS are potential alternative to the conventional method of introducing insulin to the body due to their controlled drug release mechanism. In this study, Layer-by-Layer technique was utlized to manufacture drug loaded, pH responsive thin films. Insulin was alternated with pH-sensitive, [2-(dimethyl amino ethyl aminoacrylate] (PDMAEMA and topped of with polymer/glucose oxidase (GOD layers. Similarly, films using a different polymer, namely Poly(Acrylic Acid (PAA were also fabricated. Exposure of the films to glucose solutions resulted to the production of gluconic acid causing a polymer conformation change due to protonation, thus releasing the embedded insulin. The insulin release was monitored by subjecting the dipping glucose solutions to Bradford Assay. Films exhibited a reversal in drug release profile in the presence of glucose as compared to without glucose. PAA films were also found out to release more insulin compared to that of the PDMAEMA films.The difference in the profile of the two films were due to different polymer-GOD interactions, since both films exhibited almost identical profiles when embedded with Poly(sodium 4-styrenesulfonate (PSS instead of GOD.

  8. Lack of effect of long-term amlodipine on insulin sensitivity and plasma insulin in obese patients with essential hypertension

    DEFF Research Database (Denmark)

    de Courten, Maximilian; Ferrari, P; Schneider, M;

    1993-01-01

    To evaluate the effects of long-term treatment antihypertensive with the dihydropyridine calcium antagonist amlodipine on insulin sensitivity, plasma insulin, and lipoprotein metabolism in obese hypertensive patients. We measured the insulin sensitivity index (SI), determined by the Minimal Model...... Method of Bergman, fasting plasma insulin and glucose concentrations, serum total triglyceride and lipoprotein cholesterol fractions, and blood pressure in 20 obese, non-diabetic patients with essential hypertension before and after 6 weeks of placebo and again after 6 months of amlodipine. Ten patients...... once daily in 14 patients who were hypertensive after 8 weeks on the lower dosage. At entry (before placebo), SI was slightly but not significantly lower in group A than B [2.7 vs. 3.6 x 10(-4) ml.microU-4.min-1]; fasting plasma insulin was 13.6 vs. 12.9 microU.ml-1. After 6 weeks on placebo, S1...

  9. Variable Hepatic Insulin Clearance with Attendant Insulinemia is the Primary Determinant of Insulin Sensitivity in the Normal Dog

    OpenAIRE

    Ader, Marilyn; Stefanovski, Darko; Kim, Stella P.; Richey, Joyce M.; Ionut, Viorica; Catalano, Karyn J.; Hucking, Katrin; Ellmerer, Martin; Van Citters, Gregg; Hsu, Isabel R.; Chiu, Jenny D.; Woolcott, Orison O.; Lisa N Harrison; Zheng, Dan; Lottati, Maya

    2013-01-01

    OBJECTIVE Insulin resistance is a powerful risk factor for Type 2 diabetes and a constellation of chronic diseases, and is most commonly associated with obesity. We examined if factors other than obesity are more substantial predictors of insulin sensitivity under baseline, non-stimulated conditions. DESIGN AND METHODS Metabolic assessment was performed in healthy dogs (n=90). Whole-body sensitivity from euglycemic clamps (SICLAMP) was the primary outcome variable, and was measured independen...

  10. Vitamin D3 supplementation improves insulin sensitivity in subjects with impaired fasting glucose

    OpenAIRE

    Nazarian, Shaban; Peter, John V St; Boston, Raymond C; Jones, Sidney A; Mariash, Cary N

    2011-01-01

    Vitamin D has in vitro and in vivo effects on β-cells and insulin sensitivity. Vitamin D deficiency (VDD) has been associated with onset and progression of type 2 diabetes mellitus (DM-2). However, studies involving supplementation of vitamin D in subjects with previously established diabetes have demonstrated inconsistent effects on insulin sensitivity. The aim of this open-label study was to assess the effects of high dose vitamin D3 supplementation on insulin sensitivity in subjects with V...

  11. Human skeletal muscle ceramide content is not a major factor in muscle insulin sensitivity

    DEFF Research Database (Denmark)

    Skovbro, M; Baranowski, M; Skov-Jensen, C;

    2008-01-01

    AIMS/HYPOTHESIS: In skeletal muscle, ceramides may be involved in the pathogenesis of insulin resistance through an attenuation of insulin signalling. This study investigated total skeletal muscle ceramide fatty acid content in participants exhibiting a wide range of insulin sensitivities. METHODS...

  12. Effects of insulin sensitizers on plaque vulnerability associated with elevated lipid content in atheroma in ApoE-knockout mice.

    Science.gov (United States)

    Cefalu, W T; Wang, Z Q; Schneider, D J; Absher, P M; Baldor, L C; Taatjes, D J; Sobel, B E

    2004-03-01

    Acute coronary syndromes are generally precipitated by rupture of lipid-laden, relatively acellular, vulnerable atherosclerotic plaques with thin fibrous caps. We investigated whether a high-fat diet alters insulin sensitivity and whether insulin sensitizers (troglitazone and rosiglitazone) alter the composition of otherwise lipidladen atherosclerotic plaques in mice deficient in apolipoprotein E (ApoE). ApoE-knockout mice were fed a high-fat (n=30) or standard chow (n=10) diet for two weeks. Thereafter, those fed the high-fat diet were treated with troglitazone (n=10), rosiglitazone (n=10) or no drug (n=10) for 16 weeks beginning at 8 weeks of age. Carbohydrate metabolism was assessed with intraperitoneal glucose tolerance tests and insulin tolerance tests. Plaque composition was characterised with confocal laser scanning microscopy. The high-fat diet induced insulin resistance in the absence of weight gain. Compared with control animals on the high-fat diet, animals given troglitazone (400 mg/kg/day) or rosiglitazone (4 mg/kg/day) had significantly less area under the curve (AUC) for insulin ( p<0.05) and glucose disposal ( p<0.05). Despite significant increases in insulin sensitivity with drug treatment, no change in HDL-cholesterol and triglyceride levels, nor reduction in atheroma size or lipid content was noted. Thus, improvement in insulin resistance induced by a high-fat diet in this animal model of vasculopathy did not alter plaque composition.

  13. Correlations between insulin sensitivity and bone mineral density in non-diabetic men

    DEFF Research Database (Denmark)

    Abrahamsen, Bo; Rohold, A; Henriksen, J E;

    2000-01-01

    AIMS: To investigate relationships between bone mineral density (BMD), insulin secretion and insulin sensitivity, controlling for body composition, in view of data suggesting that hyperglycaemia [corrected] leads to decreased osteoblast proliferation and a negative calcium balance and that insulin...... sensitivity (Si) was estimated as the rate of glucose disappearance divided by the area under the insulin curve during an intravenous glucose tolerance test. RESULTS: Insulin and C-peptide levels were not correlated with BMD, but Si was a significant predictor of femur (log, r = 0.35) and WB BMD (log r = 0...

  14. Proximity to Delivery Alters Insulin Sensitivity and Glucose Metabolism in Pregnant Mice

    OpenAIRE

    Musial, Babara; Fernandez-Twinn, Denise S.; Owen R Vaughan; Ozanne, Susan E.; Voshol, Peter; Sferruzzi-Perri, Amanda N.; Fowden, Abigail L.

    2016-01-01

    In late pregnancy, maternal insulin resistance occurs to support fetal growth but little is known about insulin-glucose dynamics close to delivery. This study measured insulin sensitivity in mice in late pregnancy, day (D) 16, and near term, D19, (term 20.5D). Non-pregnant (NP) and pregnant mice were assessed for metabolite and hormone concentrations, body composition by dual energy X-ray absorptiometry, tissue insulin signalling protein abundance by Western blotting, glucose tolerance and ut...

  15. High alanine aminotransferase is associated with decreased hepatic insulin sensitivity and predicts the development of type 2 diabetes

    DEFF Research Database (Denmark)

    Vozarova, Barbora; Stefan, Norbert; Lindsay, Robert S;

    2002-01-01

    It has been proposed that liver dysfunction may contribute to the development of type 2 diabetes. The aim of the present study was to examine whether elevated hepatic enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], or gamma -glutamyltranspeptidase [GGT]) are associated...... with prospective changes in liver or whole-body insulin sensitivity and/or insulin secretion and whether these elevated enzymes predict the development of type 2 diabetes in Pima Indians. We measured ALT, AST, and GGT in 451 nondiabetic (75-g oral glucose tolerance test) Pima Indians (aged 30 +/- 6 years, body fat......-sectionally associated with obesity and whole-body and hepatic insulin resistance and prospectively associated with a decline in hepatic insulin sensitivity and the development of type 2 diabetes. Our findings indicate that high ALT is a marker of risk for type 2 diabetes and suggest a potential role of the liver...

  16. Interfacial adsorption of insulin - Conformational changes and reversibility of adsorption

    NARCIS (Netherlands)

    Mollmann, SH; Jorgensen, L; Bukrinsky, JT; Elofsson, U; Norde, W; Frokjaer, S

    2006-01-01

    The adsorption of human insulin to Teflon particles was studied with respect to conformational changes and the reversibility of adsorption was examined by total internal reflection fluorescence (TIRF). Adsorption isotherms for the adsorption of human insulin indicated high affinity adsorption, even

  17. Interfacial adsorption of insulin. Conformational changes and reversibility of adsorption

    NARCIS (Netherlands)

    Mollmann, S.H.; Bukrinsky, J.T.; Elofsson, U.; Norde, W.; Frokjaer, S.

    2006-01-01

    The adsorption of human insulin to Teflon particles was studied with respect to conformational changes and the reversibility of adsorption was examined by total internal reflection fluorescence (TIRF). Adsorption isotherms for the adsorption of human insulin indicated high affinity adsorption, even

  18. Researching Effective Strategies to Improve Insulin Sensitivity in Children and Teenagers - RESIST. A randomised control trial investigating the effects of two different diets on insulin sensitivity in young people with insulin resistance and/or pre-diabetes.

    Directory of Open Access Journals (Sweden)

    De Sukanya

    2010-09-01

    Full Text Available Abstract Background Concomitant with the rise in childhood obesity there has been a significant increase in the number of adolescents with clinical features of insulin resistance and prediabetes. Clinical insulin resistance and prediabetes are likely to progress to type 2 diabetes and early atherosclerosis if not targeted for early intervention. There are no efficacy trials of lifestyle intervention in this group to inform clinical practice. The primary aim of this randomised control trial (RCT is to determine the efficacy and effectiveness of two different structured lifestyle interventions differing in diet composition on insulin sensitivity, in adolescents with clinical insulin resistance and/or prediabetes treated with metformin. Methods/design This study protocol describes the design of an ongoing RCT. We are recruiting 108 (54 each treatment arm 10 to 17 year olds with clinical features of insulin resistance and/or prediabetes, through physician referral, into a multi-centred RCT. All participants are prescribed metformin and participate in a diet and exercise program. The lifestyle program is the same for all participants except for diet composition. The diets are a high carbohydrate, low fat diet and a moderate carbohydrate, increased protein diet. The program commences with an intensive 3 month dietary intervention, implemented by trained dietitians, followed by a 3 month intensive gym and home based exercise program, supervised by certified physical trainers. To measure the longer term effectiveness, after the intensive intervention trial participants are managed by either their usual physician or study physician and followed up by the study dietitians for an additional 6 months. The primary outcome measure, change in insulin sensitivity, is measured at 3, 6 and 12 months. Discussion Clinical insulin resistance and prediabetes in the paediatric population are rapidly emerging clinical problems with serious health outcomes. With

  19. Ethnic Differences in Insulin Sensitivity, β-Cell Function, and Hepatic Extraction Between Japanese and Caucasians

    DEFF Research Database (Denmark)

    Møller, Jonas B; Dalla Man, Chiara; Overgaard, Rune V;

    2014-01-01

    a cross-sectional study with oral glucose tolerance tests to assess β-cell function, hepatic insulin extraction, and insulin sensitivity. PARTICIPANTS: PARTICIPANTS included 120 Japanese and 150 Caucasian subjects. MAIN OUTCOMES: Measures of β-cell function, hepatic extraction, and insulin...... sensitivity were assessed using C-peptide, glucose, and insulin minimal models. RESULTS: Basal β-cell function (Φ(b)) was lower in Japanese compared with Caucasians (P < .01). In subjects with IGT, estimates of the dynamic (Φ(d)) and static (Φ(s)) β-cell responsiveness were significantly lower in the Japanese...... compared with Caucasians (P < .05). In contrast, values of insulin action showed higher sensitivity in the Japanese IGT subjects. Hepatic extraction was similar in NGT and IGT groups but higher in Japanese type 2 diabetic subjects (P < .01). Despite differences in insulin sensitivity, β-cell function, and...

  20. A two-week reduction of ambulatory activity attenuates peripheral insulin sensitivity

    DEFF Research Database (Denmark)

    Krogh-Madsen, Rikke; Thyfault, John P; Broholm, Christa;

    2009-01-01

    activity would influence peripheral insulin sensitivity. We aimed to explore if healthy, non-exercising subjects who went from a normal to a low level of ambulatory activity for two weeks would display metabolic alterations including reduced peripheral insulin sensitivity. -To do this, ten healthy young...... number of daily steps induced a significant reduction of 17% in the glucose infusion rate (GIR) during the clamp. This reduction was due to a decline in peripheral insulin sensitivity with no effect on hepatic endogenous glucose production. The insulin-stimulated ratio of pAkt(thr308)/total Akt decreased...... possible biological cause for the public health problem of type 2 diabetes has been identified. Reduced ambulatory activity for two weeks in healthy, non-exercising young men significantly reduced peripheral insulin sensitivity, cardiovascular fitness, and lean leg mass. Key words: Inactivity, Insulin...

  1. Identification of adipokine clusters related to parameters of fat mass, insulin sensitivity and inflammation.

    Directory of Open Access Journals (Sweden)

    Gesine Flehmig

    Full Text Available In obesity, elevated fat mass and ectopic fat accumulation are associated with changes in adipokine secretion, which may link obesity to inflammation and the development of insulin resistance. However, relationships among individual adipokines and between adipokines and parameters of obesity, glucose metabolism or inflammation are largely unknown. Serum concentrations of 20 adipokines were measured in 141 Caucasian obese men (n = 67 and women (n = 74 with a wide range of body weight, glycemia and insulin sensitivity. Unbiased, distance-based hierarchical cluster analyses were performed to recognize patterns among adipokines and their relationship with parameters of obesity, glucose metabolism, insulin sensitivity and inflammation. We identified two major adipokine clusters related to either (1 body fat mass and inflammation (leptin, ANGPTL3, DLL1, chemerin, Nampt, resistin or insulin sensitivity/hyperglycemia, and lipid metabolism (vaspin, clusterin, glypican 4, progranulin, ANGPTL6, GPX3, RBP4, DLK1, SFRP5, BMP7, adiponectin, CTRP3 and 5, omentin. In addition, we found distinct adipokine clusters in subgroups of patients with or without type 2 diabetes (T2D. Logistic regression analyses revealed ANGPTL6, DLK1, Nampt and progranulin as strongest adipokine correlates of T2D in obese individuals. The panel of 20 adipokines predicted T2D compared to a combination of HbA1c, HOMA-IR and fasting plasma glucose with lower sensitivity (78% versus 91% and specificity (76% versus 94%. Therefore, adipokine patterns may currently not be clinically useful for the diagnosis of metabolic diseases. Whether adipokine patterns are relevant for the predictive assessment of intervention outcomes needs to be further investigated.

  2. Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study

    DEFF Research Database (Denmark)

    Tabák, A.G.; Jokela, M.; Akbaraly, T.N.;

    2009-01-01

    assessed retrospective trajectories of fasting and 2-h postload glucose, homoeostasis model assessment (HOMA) insulin sensitivity, and HOMA beta-cell function from up to 13 years before diabetes diagnosis (diabetic group) or at the end of follow-up (non-diabetics). FINDINGS: Multilevel models adjusted...... for age, sex, and ethnic origin confirmed that all metabolic measures followed linear trends in the group of non-diabetics (10,989 measurements), except for insulin secretion that did not change during follow-up. In the diabetic group (801 measurements), a linear increase in fasting glucose was followed...

  3. Insulin's acute effects on glomerular filtration rate correlate with insulin sensitivity whereas insulin's acute effects on proximal tubular sodium reabsorption correlate with salt sensitivity in normal subjects

    NARCIS (Netherlands)

    ter Maaten, JC; Bakker, SJL; Serne, EH; ter Wee, PM; Gans, ROB

    1999-01-01

    Background. Insulin induces increasing distal tubular sodium reabsorption. Opposite effects of insulin to offset insulin-induced sodium retention are supposedly increases in glomerular filtration rate (GFR) and decreases in proximal tubular sodium reabsorption. Defects in these opposing effects coul

  4. Central GLP-2 enhances hepatic insulin sensitivity via activating PI3K signaling in POMC neurons

    Science.gov (United States)

    Glucagon-like peptides (GLP-1/GLP-2) are coproduced and highlighted as key modulators to improve glucose homeostasis and insulin sensitivity after bariatric surgery. However, it is unknown if CNS GLP-2 plays any physiological role in the control of glucose homeostasis and insulin sensitivity. We sho...

  5. Importance of hepatitis C virus-associated insulin resistance:Therapeutic strategies for insulin sensitization

    Institute of Scientific and Technical Information of China (English)

    Takumi; Kawaguchi; Michio; Sata

    2010-01-01

    Insulin resistance is one of the pathological features in patients with hepatitis C virus(HCV) infection.Generally,persistence of insulin resistance leads to an increase in the risk of life-threatening complications such as cardiovascular diseases.However,these complications are not major causes of death in patients with HCV-associated insulin resistance.Indeed,insulin resistance plays a crucial role in the development of various complications and events associated with HCV infection.Mounting evidence indic...

  6. Relationship between Inflammation markers, Coagulation Activation and Impaired Insulin Sensitivity in Obese Healthy Women

    International Nuclear Information System (INIS)

    Obesity, insulin resistance syndrome, and atherosclerosis are closely linked phenomena, often connected with a chronic low grade inflammatory state and pro thrombotic hypo fibrinolytic condition. This study investigated the relationship between impaired insulin sensitivity and selected markers of inflammation and thrombin generation in obese healthy women. The study included 36 healthy obese women (body mass index ≥ 30), with normal insulin sensitivity (NIS, n = 18) or impaired insulin sensitivity (IIS, n 18), and 10 non obese women (body mass index < 25).Impaired insulin sensitivity patients had significantly higher levels of high sensitivity C-reactive protein (hs-CRP), transforming growth factor -β1(TGF-β1), plasminogen activator inhibitor-1 (PAI-1), activated factor VII (VIIa), and prothrombin fragments 1 + 2 (F1 + 2) compared with either control subjects or normal insulin sensitivity patients. On the other hand, NIS patients had higher hs-CRP, TGF-β1, PAI-1, and factor VIIa, but not F1 + 2, levels than controls. Significant inverse correlations were observed between the insulin sensitivity index and TGF-β1, hs-CRP, PAI-1; factor VIIa, and F1 + 2 levels. Moreover, significant direct correlations were noted between TGF-β1 and CRP, PAI-1, factor VIIa, and F1 + 2 concentrations. Finally, multiple regressions revealed that TGF-β1 and the insulin sensitivity index were independently related to F1 + 2. These results document an in vivo relationship between insulin sensitivity and coagulation activation in obesity. Here we report that obesity is associated with higher TGF-β, PAI-1, prothrombin fragments 1 and 2 (F1 + 2), and activated factor VII (VIIa) plasma levels, and that insulin resistance exacerbates these alterations. The elevated TGF-β1 levels detected in the obese population may provide a biochemical link between insulin resistance and an increased risk for cardiovascular disease

  7. Neuronal Sirt1 Deficiency Increases Insulin Sensitivity in Both Brain and Peripheral Tissues*

    Science.gov (United States)

    Lu, Min; Sarruf, David A.; Li, Pingping; Osborn, Olivia; Sanchez-Alavez, Manuel; Talukdar, Saswata; Chen, Ai; Bandyopadhyay, Gautam; Xu, Jianfeng; Morinaga, Hidetaka; Dines, Kevin; Watkins, Steven; Kaiyala, Karl; Schwartz, Michael W.; Olefsky, Jerrold M.

    2013-01-01

    Sirt1 is a NAD+-dependent class III deacetylase that functions as a cellular energy sensor. In addition to its well-characterized effects in peripheral tissues, emerging evidence suggests that neuronal Sirt1 activity plays a role in the central regulation of energy balance and glucose metabolism. To assess this idea, we generated Sirt1 neuron-specific knockout (SINKO) mice. On both standard chow and HFD, SINKO mice were more insulin sensitive than Sirt1f/f mice. Thus, SINKO mice had lower fasting insulin levels, improved glucose tolerance and insulin tolerance, and enhanced systemic insulin sensitivity during hyperinsulinemic euglycemic clamp studies. Hypothalamic insulin sensitivity of SINKO mice was also increased over controls, as assessed by hypothalamic activation of PI3K, phosphorylation of Akt and FoxO1 following systemic insulin injection. Intracerebroventricular injection of insulin led to a greater systemic effect to improve glucose tolerance and insulin sensitivity in SINKO mice compared with controls. In line with the in vivo results, insulin-induced AKT and FoxO1 phosphorylation were potentiated by inhibition of Sirt1 in a cultured hypothalamic cell line. Mechanistically, this effect was traced to a reduced effect of Sirt1 to directly deacetylate and repress IRS-1 function. The enhanced central insulin signaling in SINKO mice was accompanied by increased insulin receptor signal transduction in liver, muscle, and adipose tissue. In summary, we conclude that neuronal Sirt1 negatively regulates hypothalamic insulin signaling, leading to systemic insulin resistance. Interventions that reduce neuronal Sirt1 activity have the potential to improve systemic insulin action and limit weight gain on an obesigenic diet. PMID:23457303

  8. Association of obesity and insulin resistance with asthma and aeroallergen sensitization

    DEFF Research Database (Denmark)

    Husemoen, L L N; Glümer, C; Lau, C;

    2008-01-01

    BACKGROUND: It has been hypothesized that obesity and insulin resistance may play a role in the development of asthma and allergy. The aim of the study was to examine the association of obesity and insulin resistance with asthma and aeroallergen sensitization. METHODS: Cross-sectional population...... and aeroallergen sensitization. The homeostasis model assessment of insulin resistance was used to estimate the degree of insulin resistance. Body mass index, waist-to-hip ratio, and waist circumference were used as measures of obesity. Data were analyzed by multiple logistic regression analyses. RESULTS: Obesity...... was associated with increased risk of aeroallergen sensitization as well as allergic and nonallergic asthma. Insulin resistance was asssociated with aeroallergen sensitization and allergic asthma, but not nonallergic asthma. The associations of obesity with aeroallegen sensitization and allergic asthma became...

  9. Prior AICAR stimulation increases insulin sensitivity in mouse skeletal muscle in an AMPK-dependent manner

    DEFF Research Database (Denmark)

    Kjøbsted, Rasmus; Treebak, Jonas Thue; Fentz, Joachim;

    2015-01-01

    Acute exercise increases glucose uptake in skeletal muscle by an insulin-independent mechanism. In the period after exercise insulin sensitivity to increase glucose uptake is enhanced. The molecular mechanisms underpinning this phenomenon are poorly understood, but appear to involve an increased...... AMPK activation increases skeletal muscle insulin sensitivity. We found that prior AICAR stimulation of wild-type mouse muscle increases insulin sensitivity to stimulate glucose uptake. However, this was not observed in mice with reduced or ablated AMPK activity in skeletal muscle. Furthermore, prior...... AICAR stimulation enhanced insulin-stimulated phosphorylation of TBC1D4 at Thr(649) and Ser(711) in wild-type muscle only. These phosphorylation events were positively correlated with glucose uptake. Our results provide evidence to support that AMPK is sufficient to increase skeletal muscle insulin...

  10. Changes in 125I-insulin binding antibodies in diabetic pregnant women on insulin therapy and hypoglycemia in newborns

    International Nuclear Information System (INIS)

    To elucidate whether insulin antibodies in pregnant diabetics are related to changes in insulin requirement during pregnancy, and whether hypoglycemia in newborns of diabetic mothers is influenced by insulin antibodies transferred through the placenta, changes in 125I-insulin percent binding to insulin antibodies were measured at the first, second and third trimesters of pregnancy and at delivery, in 20 deliveries by 17 diabetics treated with insulin. The free insulin levels in the same serum were also measured for each patient in whom the 125I-insulin binding was decreased more than 5% in the third trimester. The mean percent of 125I-insulin binding in the 20 diabetic pregnancies was unchanged in the first (21.2%) and second trimester (21.1%), but tended to decrease to 17.6% in the third trimester and to increase to 24.6% after delivery. The 125I-insulin percent binding of 5 patients with neonatal hypoglycemia was significantly higher than that of the other patients without hypoglycemia (p125I-insulin percent binding was decreased in the third trimester in contrast with an increased insulin dosage. The finding that hypoglycemia tended to occur in the newborns of diabetic mothers with high insulin percent binding to insulin antibody during the third trimester, suggests that maternal insulin antibodies may affect the fetal pancreas. (author)

  11. Common genetic variation in the human CTF1 locus, encoding cardiotrophin-1, determines insulin sensitivity.

    Directory of Open Access Journals (Sweden)

    Stefan Z Lutz

    Full Text Available AIMS/HYPOTHESIS: Recently, cardiotrophin-1, a member of the interleukin-6 family of cytokines was described to protect beta-cells from apoptosis, to improve glucose-stimulated insulin secretion and insulin resistance, and to prevent streptozotocin-induced diabetes in mice. Here, we studied whether common single nucleotide polymorphisms (SNPs in the CTF1 locus, encoding cardiotrophin-1, influence insulin secretion and insulin sensitivity in humans. METHODS: We genotyped 1,771 German subjects for three CTF1 tagging SNPs (rs1046276, rs1458201, and rs8046707. The subjects were metabolically characterized by an oral glucose tolerance test. Subgroups underwent magnetic resonance (MR imaging/spectroscopy and hyperinsulinaemic-euglycaemic clamps. RESULTS: After appropriate adjustment, the minor allele of CTF1 SNP rs8046707 was significantly associated with decreased in vivo measures of insulin sensitivity. The other tested SNPs were not associated with OGTT-derived sensitivity parameters, nor did the three tested SNPs show any association with OGTT-derived parameters of insulin release. In the MR subgroup, SNP rs8046707 was nominally associated with lower visceral adipose tissue. Furthermore, the SNP rs1458201 showed a nominal association with increased VLDL levels. CONCLUSIONS: In conclusion, this study, even though preliminary and awaiting further confirmation by independent replication, provides first evidence that common genetic variation in CTF1 could contribute to insulin sensitivity in humans. Our SNP data indicate an insulin-desensitizing effect of cardiotrophin-1 and underline that cardiotrophin-1 represents an interesting target to influence insulin sensitivity.

  12. Human gut microbes impact host serum metabolome and insulin sensitivity

    DEFF Research Database (Denmark)

    Pedersen, Helle Krogh; Gudmundsdottir, Valborg; Nielsen, Henrik Bjørn;

    2016-01-01

    Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant individ......Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin......-resistant individuals is characterized by increased levels of branched-chain amino acids (BCAAs), which correlate with a gut microbiome that has an enriched biosynthetic potential for BCAAs and is deprived of genes encoding bacterial inward transporters for these amino acids. Prevotella copri and Bacteroides vulgatus...

  13. Impact of Major Depressive Disorder on Prediabetes by Impairing Insulin Sensitivity

    Science.gov (United States)

    Li, Li; Shelton, Richard Charles; Chassan, Rachel Ann; Hammond, John Charles; Gower, Barbara Ann; Garvey, Timothy W

    2016-01-01

    Reports regarding the associations between major depressive disorder (MDD) and diabetes remain heterogeneous. Our aim was to investigate whether glucose homeostasis and insulin sensitivity were impaired in the MDD patients and its mechanisms. A total of 30 patients with MDD and 30 matched controls were recruited. The oral glucose tolerance test and dual-energy X-ray absorptiometry scan were performed in each participant. Insulin signaling in postmortem brain tissues from other depressive patients and controls (obtained from Alabama brain bank) was examined. Insulin sensitivity was reduced substantially in the MDD patients, however, the fasting and 2-h glucose concentrations remained within the normal range through compensatory insulin secretion. Despite increased insulin secretion, 1-h glucose concentrations in the MDD patients were significantly elevated compared with the controls. MDD patients had greater visceral fat mass but lower adiponectin levels compared with the controls. Furthermore, phosphorylated-AKT levels in insulin signaling were decreased in postmortem brain tissues in patients with MDD. These results suggest that MDD patients are at a greater risk for diabetes due to decreased insulin sensitivity, reduced disposition index, and impaired glucose tolerance as manifested by elevated 1-h glucose concentrations following an oral glucose challenge. Mechanistic studies reveal that decreased insulin sensitivity is associated with increased visceral fat mass, lower adiponectin levels and impaired insulin action in postmortem brain tissues in the MDD patients. Our findings emphasize the importance of screening depressive patients to identify susceptible individuals for developing future diabetes with the hope of improving their health outcomes. PMID:27274905

  14. Insulin-Induced Electrophysiology Changes in Human Pleura Are Mediated via Its Receptor

    OpenAIRE

    V. K. Kouritas; Ioannou, M.; Foroulis, C. N.; Desimonas, N.; K. Evaggelopoulos; Gourgoulianis, K. I.; Molyvdas, P A; Hatzoglou, C.

    2010-01-01

    Background. Insulin directly changes the sheep pleural electrophysiology. The aim of this study was to investigate whether insulin induces similar effects in human pleura, to clarify insulin receptor's involvement, and to demonstrate if glibenclamide (hypoglycemic agent) reverses this effect. Methods. Human parietal pleural specimens were mounted in Ussing chambers. Solutions containing insulin or glibenclamide and insulin with anti-insulin antibody, anti-insulin receptor antibody, and gl...

  15. EFFECT OF CHRONIC ACE INHIBITION ON GLUCOSE TOLERANCE AND INSULIN SENSITIVITY IN HYPERTENSIVE TYPE 2 DIABETIC PATIENTS

    Institute of Scientific and Technical Information of China (English)

    尹卫东; G.Seghieri; C.Boni,G,Sanna; R.Anichinl; G.Bartolomei; E.Ferrannini

    1994-01-01

    We studied 14 moderately overweight Type 2 diabetic patients with essential hypertension in stable metabolic control after a run-in period,and again after 3 months of antihypertensive treatment with the angiotensin-convert-ing enzyme(ACE)inhibitor captopril.Glucose tolerance was tested with a 75g oral glucose load (OGTT) and in-sulin sensitivity was measured by the insulin suppression test (IST)while dietary and drug treatment of the hyper-glycemia was maintained constant.In the whole group,mean blood pressure (MBP) fell progressively over 3 months from a baseline value of 123±3mmHg(1 mmHg=0.133kpa)to a final value of 115±2mmHg(P<0.005).After treatment,fasting plasma glucose,insulin,free fatty acid (FFA),potassium,and glycosylated hemoglobin concentrations were unchanged from baseling.There were no significant differences in glucose toler-ance and insulin sensitivity between pre-and post-trearment values.Neither endogenous (oral glucose)nor exoge-nous(IST)insulin caused any change in plasma potassium concentration. This resistance to the hypokalemic action of insulin was not affected by captopril.

  16. Five-year weight changes associate with blood pressure alterations independent of changes in serum insulin

    DEFF Research Database (Denmark)

    Seven, Ekim; Husemoen, Lise L N; Wachtell, Kristian;

    2014-01-01

    OBJECTIVE: In overweight-related hypertension, the effect of weight changes on blood pressure (BP) is believed to be mediated by insulin. To test this hypothesis, we studied 5-year changes in weight, BP, and insulin in a general population of Danish adults (n = 3443; mean age 45.7 ± 7.6 years). M...... of the insulin variables was significantly associated with SBP or DBP (P ≥ 0.08). The results for changes in DBP were similar to SBP. CONCLUSION: Five-year weight changes associate with BP alterations independent of the insulin changes....

  17. Effects of chronic calorie restriction or dietary resveratrol supplementation on insulin sensitivity markers in a primate, Microcebus murinus.

    Directory of Open Access Journals (Sweden)

    Julia Marchal

    Full Text Available The prevalence of diabetes and hyperinsulinemia increases with age, inducing metabolic failure and limiting lifespan. Calorie restriction (CR without malnutrition delays the aging process, but its long-term application to humans seems difficult. Resveratrol (RSV, a dietary polyphenol, appears to be a promising CR mimetic that can be easily administered in humans. In this work, we hypothesized that both CR and RSV impact insulin sensitivity in a non-human primate compared to standard-fed control (CTL animals. Four- to five-year-old male grey mouse lemurs (Microcebus murinus were assigned to three dietary groups: a CTL group, a CR group receiving 30% fewer calories than the CTL and a RSV group receiving the CTL diet supplemented with RSV (200 mg·day(-1·kg(-1. Insulin sensitivity and glycemia were assessed using an oral glucose tolerance test (OGTT and the homeostasis model assessment of insulin resistance (HOMA-IR index evaluation after 21 or 33 months of chronic treatment. Resting metabolic rate was also measured to assess the potential relationships between this energy expenditure parameter and insulin sensitivity markers. No differences were found after a 21-month period of treatment, except for lower glucose levels 30 min after glucose loading in CR animals. After 33 months, CR and RSV decreased glycemia after the oral glucose loading without decreasing fasting blood insulin. A general effect of treatment was observed on the HOMA-IR index, with an 81% reduction in CR animals and 53% in RSV animals after 33 months of treatment compared to CTL. Chronic CR and dietary supplementation with RSV affected insulin sensitivity by improving the glucose tolerance of animals without disturbing their baseline insulin secretion. These results suggest that both CR and RSV have beneficial effects on metabolic alterations, although these effects are different in amplitude between the two anti-aging treatments and potentially rely on different metabolic

  18. Ageing related changes of insulin secretion and insulin sensitivity among normal glucose tolerance individuals in China%中国正常糖耐量人群胰岛功能及胰岛素敏感性随增龄的变化

    Institute of Scientific and Technical Information of China (English)

    朱海清; 杨兆军; 张波; 萧建中; 杨文英

    2012-01-01

    目的 探讨中国正常糖耐量人群(NGT)胰岛功能及胰岛素敏感性随增龄的变化.方法 以2007-2008年全国糖尿病及代谢综合征患病率变迁调查中的34 293例正常糖耐量者为研究对象,受试者行75 g口服葡萄糖耐量试验,测量血糖、胰岛素水平.按照1999年WHO诊断标准确定正常糖耐量人群,并计算稳态模型法胰岛β细胞分泌指数(HOMA-β)、胰岛素早期分泌指数(△I30/△G30)、30 min胰岛素分泌曲线下面积/30 min血糖曲线下面积(InsAuc30/GluAuc30)、120 min分泌量(InsAuc120/GluAuc120),胰岛素抵抗指数及敏感性指数(HOMA-IR、Matsuda指数)、血糖处置指数(DI30、DI120).结果 NGT人群中HOMA-β及△I30/△G30、InsAuc30/GluAuc30、InsAuc120/GluAuc120随增龄而下降(P<0.05).随着年龄增长,男性中HOMA-β由192±16(20 ~29岁)降至115±7(≥70岁),女性中HOMA-β由162±8(20~29岁)降至120±12(≥70岁);△I30/△G30在男性中由20.0 ±2.0(20~29岁)降至8.6±0.6(≥70岁),女性中由22.4±1.6(20 ~29岁)降至12.5±1.7(≥70岁),线性回归结果发现以上反映胰岛素分泌的指标与年龄呈负相关(P<0.05),但方程中校正体质指数( BMI)及腰围后在女性中HOMA-β与年龄无相关.在男性中HOMA-IR与年龄呈负相关(β=-0.01,P=0.001),Matsuda指数与年龄呈正相关(β=0.02,P=0.001),在回归方程中校正了BMI、腰围的影响后,以上结果仍然有统计学意义;在女性中HOMA-IR 和Matsuda指数与年龄无相关,校正了肥胖相关指标的影响后,HOMA-IR与年龄呈负相关(β=-0.01,P=0.000),Matsuda指数与年龄呈正相关(β=0.03,P=0.000).而DI30、DI120无论校正BMI和腰围与否均随增龄而下降(P<0.01).结论 在中国NGT人群中,基础及口服葡萄糖负荷后胰岛素分泌,胰岛代偿功能均随增龄而下降;但胰岛素敏感性并未随着增龄而导致的体重及体脂分布变化而减弱.%Objective To expiore the aging-related changes of insulin

  19. Effect of Moderate Alcohol Consumption on Adiponectin, Tumor Necrosis Factor-α, and Insulin Sensitivity

    NARCIS (Netherlands)

    Sierksma, A.; Patel, H.; Ouchi, N.; Kihara, S.; Funahashi, T.; Heine, R.J.; Grobbee, D.E.; Kluft, C.; Hendriks, H.F.J.

    2004-01-01

    OBJECTIVE - Epidemiological studies suggest that moderate alcohol consumers have enhanced insulin sensitivity and a reduced risk of type 2 diabetes. Adiponectin, an adipocyte-derived plasma protein, has been found to be negatively associated with adiposity and positively associated with insulin sens

  20. Insulin sensitizing effect of 3 Indian medicinal plants: An in vitro study

    Directory of Open Access Journals (Sweden)

    Samidha A Kalekar

    2013-01-01

    Conclusion: The results suggest that one of the mechanisms for the anti-diabetic effect of Pe, Cl and Tc may be through an insulin sensitizing effect (stimulation of glucose uptake into adipocytes. Further studies using other target sites viz. skeletal muscle and hepatocytes models and in an insulin resistant state would help substantiate this conclusion.

  1. Effects of 7 days of exercise training on insulin sensitivity and responsiveness in type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Kirwan, John P; Solomon, Thomas; Wojta, Daniel M;

    2009-01-01

    The objectives of this study were to determine whether 1) the improvement in insulin action induced by short-term exercise training in patients with type 2 diabetes is due to an improvement in insulin sensitivity, an improvement in insulin responsiveness, or a combination of improved insulin sens...

  2. Lipid accumulation in overweight type 2 diabetic subjects: relationships with insulin sensitivity and adipokines.

    Science.gov (United States)

    Sambataro, Maria; Perseghin, Gianluca; Lattuada, Guido; Beltramello, Giampietro; Luzi, Livio; Pacini, Giovanni

    2013-06-01

    Adipokines are known to play a fundamental role in the etiology of obesity, that is, in the impaired balance between increased feeding and decreased energy expenditure. While the adipokine-induced changes of insulin resistance in obese diabetic and nondiabetic subjects are well known, the possible role of fat source in modulating insulin sensitivity (IS) remains controversial. The aim of our study was to explore in overweight type 2 diabetic patients (T2DM) with metabolic syndrome IS in different energy storage conditions (basal and dynamic) for relating it to leptin and adiponectin. Sixteen T2DM (5/11 F/M; 59 ± 2 years; 29.5 ± 1.1 kg/m(2)) and 16 control (CNT 5/11; 54 ± 2; 29.1 ± 1.0) underwent an oral glucose tolerance test. Fasting IS was measured by QUICKI, while the dynamic one with OGIS. The insulinogenic index (IGI) described beta cell function. Also, the lipid accumulation product parameter (LAP) was assessed. LAP accounts for visceral abdominal fat and triglycerides, and it is known to be related to IS. Possible interrelationships between LAP and adipokines were explored. In T2DM and CNT, adiponectin (7.4 ± 0.5 vs. 7.8 ± 0.9 μg/mL), leptin (13.3 ± 3.0 vs. 12.4 ± 2.6 ng/mL), and QUICKI (0.33 ± 0.01 vs. 0.33 ± 0.01) were not different (P > 0.40), at variance with OGIS (317 ± 11 vs. 406 ± 13 mL/min/m(2); P = 0.006) and IGI (0.029 ± 0.005 vs. 0.185 ± 0.029 × 10(3) pmolI/mmolG; P = 0.00001). LAP was 85 ± 15 cm × mg/dL in T2DM and 74 ± 10 in CNT (P > 0.1), correlated with OGIS in all subjects (R = -0.42, P = 0.02) and QUICKI (R = -0.56, P = 0.025) in T2DM. Leptin correlated with QUICKI (R = -0.45, P = 0.009), and adiponectin correlated with OGIS (R = 0.43, P = 0.015). In overweight T2DM, insulin sensitivity in basal condition appears to be multifaceted with respect to the dynamic one, because it should be more fat-related. Insulin sensitivity appears to be incompletely described by functions of fasting glucose and insulin values alone and the

  3. Insulin Sensitivity and β-Cell Function Improve after Gastric Bypass in Severely Obese Adolescents

    Science.gov (United States)

    Inge, Thomas H.; Prigeon, Ronald L.; Elder, Deborah A.; Jenkins, Todd M.; Cohen, Robert M.; Xanthakos, Stavra A.; Benoit, Stephen C.; Dolan, Lawrence M.; Daniels, Stephen R.; D’Alessio, David A.

    2016-01-01

    Objective To test the hypothesis that insulin secretion and insulin sensitivity would be improved in adolescents after Roux-en-Y gastric bypass (RYGB). Study design A longitudinal study of 22 adolescents and young adults without diabetes undergoing laparoscopic RYGB (mean age 17.1 ± 1.42 years; range 14.5–20.1; male/female 8/14; Non-Hispanic White/African American 17/5) was conducted. Intravenous glucose tolerance tests were done to obtain insulin sensitivity (insulin sensitivity index), insulin secretion (acute insulin response to glucose), and the disposition index as primary outcome variables. These variables were compared over the 1 year of observation using linear mixed modeling. Results In the 1-year following surgery, body mass index fell by 38% from a mean of 61 ± 12.3 to 39 ± 8.0 kg/m2 (P < .01). Over the year following surgery, fasting glucose and insulin values declined by 54% and 63%, respectively. Insulin sensitivity index increased 300% (P < .01), acute insulin response to glucose decreased 56% (P < .01), leading to a nearly 2-fold increase in the disposition index (P < .01). Consistent with improved β-cell function, the proinsulin to C-peptide ratio decreased by 21% (P < .01). Conclusions RYGB reduced body mass index and improved both insulin sensitivity and β-cell function in severely obese teens and young adults. These findings demonstrate that RYGB is associated with marked metabolic improvements in obese young people even as significant obesity persists. Trial registration ClinicalTrials.gov: NCT00360373. PMID:26363548

  4. A single night of partial sleep loss impairs fasting insulin sensitivity but does not affect cephalic phase insulin release in young men

    OpenAIRE

    Cedernaes, Jonathan; Lampola, Lauri; Axelsson, Emil K; Liethof, Lisanne; Hassanzadeh, Sara; Yeganeh, Adine; Broman, Jan-Erik; Schiöth, Helgi B; Benedict, Christian

    2016-01-01

    The present study sought to investigate whether a single night of partial sleep deprivation (PSD) would alter fasting insulin sensitivity and cephalic phase insulin release (CPIR) in humans. A rise in circulating insulin in response to food-related sensory stimulation may prepare tissues to break down ingested glucose, e.g. by stimulating rate-limiting glycolytic enzymes. In addition, given insulin's anorexigenic properties once it reaches the brain, the CPIR may serve as an early peripheral ...

  5. mTORC2 Regulation of Muscle Metabolism and Insulin Sensitivity

    DEFF Research Database (Denmark)

    Kleinert, Maximilian

    Type 2 diabetes (T2D) is a pandemic that continues to grow at alarming rates. In healthy individuals, blood glucose levels are tightly controlled. After eating a meal blood glucose levels rise. This triggers insulin release from the pancreas, which in turn signals organs like the liver, fat...... is required to lower blood glucose levels. If insulin sensitivity is chronically decreased, this can stress the pancreas to the point of organ failure in genetically susceptible individuals, who therefore are unable to produce sufficient amounts of insulin. This highlights a) the importance of understanding....... In the absence of insulin, the majority of GLUT4 resides within the muscle. Conversely, insulin stimulation increases the muscle’s permeability to glucose, by triggering GLUT4 translocation to the plasma membrane. The effect of insulin on GLUT4 translocation is mediated by a chain of molecular signaling events...

  6. Effects of Lactobacillus acidophilus NCFM on insulin sensitivity and the systemic inflammatory response in human subjects

    DEFF Research Database (Denmark)

    Andreasen, Anne Sofie; Larsen, Nadja; Pedersen-Skovsgaard, Theis;

    2010-01-01

    According to animal studies, intake of probiotic bacteria may improve glucose homeostasis. We hypothesised that probiotic bacteria improve insulin sensitivity by attenuating systemic inflammation. Therefore, the effects of oral supplementation with the probiotic bacterium Lactobacillus acidophilus...

  7. Resistance training associated with the administration of anabolic-androgenic steroids improves insulin sensitivity in ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Urtado CB

    2011-11-01

    than the Sed-Intact, Sed-Ovx, and TR-Intact groups. Sed-Intact-ND and TR-Intact-ND groups exhibited higher values of insulin sensitivity than the Sed-Intact group. Except for the TR-Intact group, sensitivity was greater in trained groups than in the Sed-Intact group. There was higher insulin sensitivity in the TR-Intact-ND group than in the Sed-Intact and Sed-Intact-ND groups (P < 0.05. In conclusion, ovariectomy and short-term RT alone induced no change on insulin action. Administration of nandrolone decanoate improved insulin action, mainly when it was associated with RT.Keywords: ovariectomy, glucose, pancreas, nandrolone decanoate

  8. Why do anti-inflammatory therapies fail to improve insulin sensitivity?

    Institute of Scientific and Technical Information of China (English)

    Zhan-guo GAO; Jian-ping YE

    2012-01-01

    Chronic inflammation occurs in obese conditions in both humans and animals.It also contributes to the pathogenesis of type 2 diabetes (T2D) through insulin resistance,a status in which the body loses its ability to respond to insulin.Inflammation impairs insulin signaling through the functional inhibition of IRS-1 and PPARy.Insulin sensitizers (such as rosiglitazone and pioglitazone) inhibit inflammation while improving insulin sensitivity.Therefore,anti-inflammatory agents have been suggested as a treatment strategy for insulin resistance.This strategy has been tested in laboratory studies and clinical trials for more than 10 years; however,no significant progress has been made in any of the model systems.This status has led us to re-evaluate the biological significance of chronic inflammation in obesity.Recent studies have consistently asserted that obesity-associated inflammation helps to maintain insulin sensitivity.Inflammation stimulates local adipose tissue remodeling and promotes systemic energy expenditure.We propose that these beneficial activities of inflammation provide an underlying mechanism for the failure of anti-infiammatory therapy in the treatment of insulin resistance.Current literature will be reviewed in this article to present evidence that supports this viewpoint.

  9. Insulin-sensitizing effects of a novel α-methyl-α-phenoxylpropionate derivative in vitro

    Institute of Scientific and Technical Information of China (English)

    Hao-shu WU; Juan-hong YU; Ying-yin LI; Yu-she YANG; Qiao-jun HE; Yi-jia LOU; Ru-yun JI

    2007-01-01

    Aim: To examine the insulin sensitizing effects of a novel α-methyl-α-phenoxylpropionate derivative YY20 in insulin-sensitive cell lines. Methods: The peroxisome proliferator-activated receptorγ(PPARγ) agonist bioactivities of YY20 were detected by a preadipocyte differentiation assay. RT-PCR and Western blotting analysis were used to detect the expression of the target gene or protein.The effects of YY20 on insulin-mediated glucose consumption were determined in the HepG2 human hepatocellular carcinoma line. Results: YY20 could enhance the differentiation of preadipocytes to adipocytes and upregulate the gene ex-pression of PPAR),2, as well as the protein expression of insulin receptor sub-strate-1 (IRS-1), glucose transporter-4 (GLUT4), and adiponectin (ACRP30). The effects on GLUT4 and ACRP30 could be reversed by the PPARγinhibitor SR-202.Furthermore, YY20 efficiently reduced glucose consumptions in HepG2 cells after 24 h culture, and the effects were related to insulin and YY20 concentrations.Conclusion: YY20, a potential insulin-sensitizing agent like rosiglitazone, could enhance glucose consumption in HepG2 cells in a concentration- and insulin-dependent manner. It may improve the insulin resistance associated with type 2 diabetes.

  10. Characterization of the insulin sensitivity of ghrelin receptor KO mice using glycemic clamps

    Directory of Open Access Journals (Sweden)

    Morgan Kristen

    2011-01-01

    Full Text Available Abstract Background We and others have demonstrated previously that ghrelin receptor (GhrR knock out (KO mice fed a high fat diet (HFD have increased insulin sensitivity and metabolic flexibility relative to WT littermates. A striking feature of the HFD-fed GhrR KO mouse is the dramatic decrease in hepatic steatosis. To characterize further the underlying mechanisms of glucose homeostasis in GhrR KO mice, we conducted both hyperglycemic (HG and hyperinsulinemic-euglycemic (HI-E clamps. Additionally, we investigated tissue glucose uptake and specifically examined liver insulin sensitivity. Results Consistent with glucose tolerance-test data, in HG clamp experiments, GhrR KO mice showed a reduction in glucose-stimulated insulin release relative to WT littermates. Nevertheless, a robust 1st phase insulin secretion was still achieved, indicating that a healthy β-cell response is maintained. Additionally, GhrR KO mice demonstrated both a significantly increased glucose infusion rate and significantly reduced insulin requirement for maintenance of the HG clamp, consistent with their relative insulin sensitivity. In HI-E clamps, both LFD-fed and HFD-fed GhrR KO mice showed higher peripheral insulin sensitivity relative to WT littermates as indicated by a significant increase in insulin-stimulated glucose disposal (Rd, and decreased hepatic glucose production (HGP. HFD-fed GhrR KO mice showed a marked increase in peripheral tissue glucose uptake in a variety of tissues, including skeletal muscle, brown adipose tissue and white adipose tissue. GhrR KO mice fed a HFD also showed a modest, but significant decrease in conversion of pyruvate to glucose, as would be anticipated if these mice displayed increased liver insulin sensitivity. Additionally, the levels of UCP2 and UCP1 were reduced in the liver and BAT, respectively, in GhrR KO mice relative to WT mice. Conclusions These results indicate that improved glucose homeostasis of GhrR KO mice is

  11. Endurance training improves insulin sensitivity and body composition in prostate cancer patients treated with androgen deprivation therapy

    DEFF Research Database (Denmark)

    Hvid, Thine; Winding, Kamilla; Rinnov, Anders;

    2013-01-01

    Insulin resistance and changes in body composition are side effects of androgen deprivation therapy (ADT) given to prostate cancer patients. The present study investigated whether endurance training improves insulin sensitivity and body composition in ADT-treated prostate cancer patients. Nine me...... and magnetic resonance imaging). The secondary endpoint was systemic inflammation. Statistical analysis was carried out using two-way ANOVA. Endurance training increased VO2max (ml(O2)/min per kg) by 11 and 13% in the patients and controls respectively (P...

  12. Relationships of generalized and regional adiposity to insulin sensitivity in men.

    OpenAIRE

    Abate, N.; Garg, A.; Peshock, R M; Stray-Gundersen, J.; Grundy, S M

    1995-01-01

    The relative impacts of regional and generalized adiposity on insulin sensitivity have not been fully defined. Therefore, we investigated the relationship of insulin sensitivity (measured using hyperinsulinemic, euglycemic clamp technique with [3-3H]glucose turnover) to total body adiposity (determined by hydrodensitometry) and regional adiposity. The latter was assessed by determining subcutaneous abdominal, intraperitoneal, and retroperitoneal fat masses (using magnetic resonance imaging) a...

  13. In utero gender dimorphism of adiponectin reflects insulin sensitivity and adiposity of the fetus

    OpenAIRE

    Basu, S; Laffineuse, L.; Presley, L.; Minium, J; Catalano, PM; Hauguel-de Mouzon, S.

    2009-01-01

    Circulating adiponectin reflects the degree of energy homeostasis and insulin sensitivity of adult individuals. Low abundance of the high molecular mass multimers (HMW), the most active forms mediating the insulin-sensitizing effects of adiponectin, is indicative of impaired metabolic status. The increase in fetal adiponectin HMW compared with adults is a distinctive features of human neonates. In order to further understand the functional properties of adiponectin during fetal life, we have ...

  14. A low-fat diet improves peripheral insulin sensitivity in patients with Type 1 diabetes

    DEFF Research Database (Denmark)

    Rosenfalck, A M; Almdal, T; Viggers, L;

    2006-01-01

    To compare the effects on insulin sensitivity, body composition and glycaemic control of the recommended standard weight-maintaining diabetes diet and an isocaloric low-fat diabetes diet during two, 3-month periods in patients with Type 1 diabetes.......To compare the effects on insulin sensitivity, body composition and glycaemic control of the recommended standard weight-maintaining diabetes diet and an isocaloric low-fat diabetes diet during two, 3-month periods in patients with Type 1 diabetes....

  15. Beneficial insulin-sensitizing and vascular effects of S15261 in the insulin-resistant JCR:LA-cp rat.

    Science.gov (United States)

    Russell, J C; Ravel, D; Pégorier, J P; Delrat, P; Jochemsen, R; O'Brien, S F; Kelly, S E; Davidge, S T; Brindley, D N

    2000-11-01

    S15261, a compound developed for the oral treatment of type II diabetes, is cleaved by esterases to the fragments Y415 and S15511. The aim was to define the insulin-sensitizing effects of S15261, the cleavage products, and troglitazone and metformin in the JCR:LA-cp rat, an animal model of the obesity/insulin resistance syndrome that exhibits an associated vasculopathy and cardiovascular disease. Treatment of the animals from 8 to 12 weeks of age with S15261 or S15511 resulted in reductions in food intake and body weights, whereas Y415 had no effect. Troglitazone caused a small increase in food intake (P JCR:LA-cp rat. S15261 may thus offer effective treatment for the insulin resistance syndrome and its associated vascular complications.

  16. Co-associations between insulin sensitivity and measures of liver function, subclinical inflammation, and hematology.

    Science.gov (United States)

    Godsland, Ian F; Johnston, Desmond G

    2008-09-01

    Clustering of risk factors for coronary heart disease and diabetes is well established, particularly in relation to insulin resistance. To determine whether evaluation of risk factor clustering will contribute to risk assessment, it is first necessary to discriminate co-association between risk factors from correlation. We undertook this in a large homogenous group, using a sophisticated measure of insulin sensitivity and a broad range of risk factors. Cross-sectional analysis of an occupational cohort using regression and factor analyses was performed. Subjects were 472 apparently healthy white men. The main outcome measures were insulin sensitivity, S(I), by minimal model analysis of the intravenous glucose tolerance test plus liver function and hematologic variables, including the inflammation indices, leukocyte count, and erythrocyte sedimentation rate. The S(I) correlated independently with serum gamma-glutamyl transferase (GGT), aspartate transaminase, and alkaline phosphatase activities; blood pressure; leukocyte count; and erythrocyte sedimentation rate (P GGT activity (loadings >0.40). Mean arterial pressure was not a feature (loading 0.29), neither were indices of subclinical inflammation. In apparently healthy men, blood pressure and indices of subclinical inflammation do not cluster with other insulin resistance-related risk factors, despite correlating with insulin sensitivity. In contrast, both GGT activity and uric acid concentrations correlated with insulin sensitivity and co-associated with insulin resistance-related risk factors and are therefore components of a true risk factor cluster. PMID:18702943

  17. Effect of a 1-week, eucaloric, moderately high-fat diet on peripheral insulin sensitivity in healthy premenopausal women

    Science.gov (United States)

    Branis, Natalia M; Etesami, Marjan; Walker, Ryan W; Berk, Evan S; Albu, Jeanine B

    2015-01-01

    Objectives To determine whether a weight-maintaining, moderate (50%) high-fat diet is deleterious to insulin sensitivity in healthy premenopausal women. Design/setting/participants 23 African-American and non-Hispanic white, healthy, overweight, and obese premenopausal women recruited in New York City, USA, fed either a eucaloric, 1-week long high-fat (50% of total Kcal from fat) diet or a eucaloric, 1-week long low-fat (30% of total Kcal from fat) diet, assigned in a randomized crossover design. Main outcome measures Peripheral insulin sensitivity and metabolic flexibility during a euglycemic hyperinsulinemic (80 mU/m2/min) clamp measured during the follicular phase of the menstrual cycle, at the end of each diet period. Results Peripheral insulin sensitivity (mg kg/fat-free mass/min (µU/mL)×10−1) was not decreased after the high-fat diet vs the low-fat diet (0.09±0.01 vs 0.08±0.01, p=0.09, respectively) in the combined group of African-American and white women, with no significant diet by race interaction (p=0.6). Metabolic flexibility (change in substrate utilization, ΔNPRQ, in response to insulin during the clamp) was similarly unaltered by the diet (0.12±0.01 vs 0.11, p=0.48, for the high-fat diet vs the low-fat diet, respectively) in the combined group of women, with no significant diet by race interaction (p=0.9). African–American women had a lower insulin clearance compared with the white women, regardless of the diet (p<0.05). Conclusions We conclude that a short term (1 week), moderate (50%), eucaloric high-fat diet does not lower peripheral insulin sensitivity in healthy, overweight and obese premenopausal women. PMID:26203360

  18. Over-expression of Follistatin-like 3 attenuates fat accumulation and improves insulin sensitivity in mice

    DEFF Research Database (Denmark)

    Brandt, Claus; Hansen, Rasmus Hvass; Hansen, Jakob Bondo;

    2015-01-01

    adipose tissue. Fstl3 mice displayed improved insulin sensitivity and muscle insulin signalling. In contrast, glucose tolerance was impaired in high-fat fed fstl3 mice, which was explained by increased hepatic glucagon sensitivity and glucose output, as well as a decrease in the pancreatic insulin...

  19. The association of adipose-derived dimethylarginine dimethylaminohydrolase-2 with insulin sensitivity in experimental type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    Jie Zheng; Kuansong Wang; Ping Jin; Changsheng Dong; Qiong Yuan; Yuanjian Li; Zhichun Yang

    2013-01-01

    Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS),which can be hydrolyzed by dimethylarginine-dimethylaminohydrolase (DDAH).It has been reported that adipocytes can produce DDAH/ADMA,but its role remains unknown.In the present study,we examined the effects of adipocyte-derived DDAH/ADMA on insulin sensitivity using animal and cell models.Results showed that in adipose tissue of high fat diet-fed diabetic rats,as well as in high glucose (25 mM) plus insulin (100nM)-treated 3T3-L1 adipocytes,expression levels of insulin receptor substance-1 (IRS-1),glucose transporter-4 (GLUT-4),and DDAH isoform-2 (DDAH-2) were down-regulated compared with control,although DDAH-1 expression showed no significant changes.We also observed that nitric oxide bioavailability,DDAH and NOS activities were subsequently decreased,while the local ADMA content was elevated in diabetic adipose tissue.Transfection of human DDAH-2 gene into high glucose-and insulin-treated 3T3-L1 adipocytes significantly ameliorated DDAH activity,reduced ADMA contents,and up-regulated the mRNA expression levels of IRS-1 and GLUT-4.These findings suggested that in the development of type 2 diabetes mellitus,local DDAH-2 in adipocytes might play an important role in regulating insulin sensitivity.

  20. Enhanced insulin sensitivity associated with provision of mono and polyunsaturated fatty acids in skeletal muscle cells involves counter modulation of PP2A.

    Directory of Open Access Journals (Sweden)

    Francesca Nardi

    Full Text Available AIMS/HYPOTHESIS: Reduced skeletal muscle insulin sensitivity is a feature associated with sustained exposure to excess saturated fatty acids (SFA, whereas mono and polyunsaturated fatty acids (MUFA and PUFA not only improve insulin sensitivity but blunt SFA-induced insulin resistance. The mechanisms by which MUFAs and PUFAs institute these favourable changes remain unclear, but may involve stimulating insulin signalling by counter-modulation/repression of protein phosphatase 2A (PP2A. This study investigated the effects of oleic acid (OA; a MUFA, linoleic acid (LOA; a PUFA and palmitate (PA; a SFA in cultured myotubes and determined whether changes in insulin signalling can be attributed to PP2A regulation. PRINCIPAL FINDINGS: We treated cultured skeletal myotubes with unsaturated and saturated fatty acids and evaluated insulin signalling, phosphorylation and methylation status of the catalytic subunit of PP2A. Unlike PA, sustained incubation of rat or human myotubes with OA or LOA significantly enhanced Akt- and ERK1/2-directed insulin signalling. This was not due to heightened upstream IRS1 or PI3K signalling nor to changes in expression of proteins involved in proximal insulin signalling, but was associated with reduced dephosphorylation/inactivation of Akt and ERK1/2. Consistent with this, PA reduced PP2Ac demethylation and tyrosine307phosphorylation - events associated with PP2A activation. In contrast, OA and LOA strongly opposed these PA-induced changes in PP2Ac thus exerting a repressive effect on PP2A. CONCLUSIONS/INTERPRETATION: Beneficial gains in insulin sensitivity and the ability of unsaturated fatty acids to oppose palmitate-induced insulin resistance in muscle cells may partly be accounted for by counter-modulation of PP2A.

  1. Insulin binding changes the interface region between α subunits of the insulin receptor

    International Nuclear Information System (INIS)

    The homobifunctional cross-linking reagent disuccinimidyl suberate (DSS) was used to probe the interface region between the two α subunits of the α2β2 human insulin receptor. The two α subunits formed a covalent dimer when affinity-purified receptor or membrane-bound receptor was reacted with DSS. The α2 species was detected on protein blots from SDS gels using an anti-α-subunit antibody or 125I-concanavalin A. Alternatively, iodinated receptor was reacted with DSS and the α2 species measured directly in an SDS gel. As shown by all three assay systems, more α2 was formed when insulin was bound to receptor than when insulin was absent. These data indicate that the conformational change which occurs in the α subunit response to insulin binding results in a change in the α-α interaction within the receptor complex. The results are consistent with a kinase activation mechanism involving communication between the two αβ receptor halves

  2. A 2-wk reduction of ambulatory activity attenuates peripheral insulin sensitivity

    DEFF Research Database (Denmark)

    Krogh-Madsen, Rikke; Thyfault, John P; Broholm, Christa;

    2010-01-01

    US adults take between approximately 2,000 and approximately 12,000 steps per day, a wide range of ambulatory activity that at the low range could increase risk for developing chronic metabolic diseases. Dramatic reductions in physical activity induce insulin resistance; however, it is uncertain...... possible biological cause for the public health problem of Type 2 diabetes has been identified. Reduced ambulatory activity for 2 wk in healthy, nonexercising young men significantly reduced peripheral insulin sensitivity, cardiovascular fitness, and lean leg mass....... if and how low ambulatory activity would influence peripheral insulin sensitivity. We aimed to explore if healthy, nonexercising subjects who went from a normal to a low level of ambulatory activity for 2 wk would display metabolic alterations including reduced peripheral insulin sensitivity. To do this, ten...

  3. Peripheral insulin sensitivity as modified by diet and exercise training.

    Science.gov (United States)

    Grimditch, G K; Barnard, R J; Hendricks, L; Weitzman, D

    1988-07-01

    To determine which component of a high-fat sucrose diet (HFS) caused insulin resistance and whether exercise training or fiber could prevent it, six dietary treatments were tested in rats: low-fat complex carbohydrate (LFCC); high-fat complex carbohydrate (HFCC); low-fat sucrose (LFS); high-fat sucrose (HFS); HFS plus fiber (HFS + F); and HFS plus exercise training (HFS + EX). After 10 wk rats were subjected to an intravenous glucose-tolerance test. The HFS and HFS + F groups developed glucose intolerance, as indicated by significantly greater areas under their glucose curves compared with the LFCC group's areas. The LFS, HFS, HFS + F, and HFS + EX groups developed insulin resistance, as indicated by significantly greater areas under their insulin curves compared with the LFCC and HFCC groups' areas. Either the presence of sucrose or the absence of complex carbohydrates, not high fat, was responsible for the insulin resistance and it was not improved by adding fiber to the diet or by exercise training.

  4. Insulin sensitivity and carotid intima-media thickness

    DEFF Research Database (Denmark)

    Kozakova, Michaela; Natali, Andrea; Dekker, Jacqueline;

    2013-01-01

    Despite a wealth of experimental data in animal models, the independent association of insulin resistance with early carotid atherosclerosis in man has not been demonstrated. APPROACH AND RESULTS: We studied a European cohort of 525 men and 655 women (mean age, 44±8 years) free of conditions know...

  5. Insulin sensitivity : modulation by the gut-brain axis

    NARCIS (Netherlands)

    Heijboer, Annemieke Corine

    2006-01-01

    Er zijn steeds meer aanwijzingen dat neuropeptiden in de hypothalamus en maagdarmhormonen die hun werking hebben op de hypothalamus en betrokken zijn bij de regulatie van voedselinname, ook betrokken zouden kunnen zijn bij de regulatie van insuline gevoeligheid. Daarom hebben we eerst de effecten va

  6. Total adiponectin and adiponectin multimeric complexes in relation to weight loss-induced improvements in insulin sensitivity in obese women

    DEFF Research Database (Denmark)

    Polak, J.; Kovacova, Z.; Holst, C.;

    2008-01-01

    diet induced changes in insulin sensitivity (responders and non-responders respectively), matched for weight loss (body mass index (BMI)=34.5 (s.d. 2.9) resp. 36.5 kg/m(2) (s.d. 4.0) for responders and non-responders), were selected from 292 women who underwent a 10-week low-caloric diet (LCD; 600 kcal....../d less than energy requirements). Plasma HMW, MMW, and LMW forms of adiponectin were quantified using Western blot method. RESULTS: LCD induced comparable weight reduction in responders and non-responders by 8.2 and 7.6 kg. Homeostasis model assessment insulin resistance index decreased by 48......, and LMW were negatively associated with fasting insulin levels at baseline. CONCLUSION: No differences in total plasma adiponectin, HMW, MMW, and LMW forms were observed between responders and non-responders following 10-week LCD, suggesting that adiponectin is not a major determinant of weight loss...

  7. Changes of ghrelin following oral glucose tolerance test in obese children with insulin resistance

    Institute of Scientific and Technical Information of China (English)

    Xiu-Min Wang; You-Jun Jiang; Li Liang; Li-Zhong Du

    2008-01-01

    AIM: To characterize changes in ghrelin levels in response to oral glucose tolerance test (OGTT) and to correlate changes in ghrelin levels with changes in insulin and glucose following OGTT in Chinese obese children of Tanner I and Ⅱ stage with insulin resistance.METHODS: 22 obese children with insulin resistance state were divided into four groups according to their Tanner stage and gender: boys of Tanner I (BT-Ⅰ), boys of Tanner Ⅱ (BT- Ⅱ), girls of Tanner Ⅰ (GT-Ⅰ), girls of Tanner Ⅱ (GT-Ⅱ). Ghrelin, insulin and glucose were measured at 0, 30, 60 and 120 min following OGTT. The control children with normal BMI were divided into control boys of Tanner I (CBT-Ⅰ, n = 6), control boys of Tanner Ⅱ (CBT- Ⅱ, n = 5), control girls of Tanner I (CGT-1, n = 6), control girls of Tanner II (CGT- Ⅱ, n = 5). Fasting serum ghrelin levels were analyzed.RESULTS: Ghrelin levels were lower in obese groups. Ghrelin levels of control group decreased in Tanner Ⅱ stage (CGT-Ⅰ vs CGT-Ⅱ t = -4.703, P = 0.001; CBT-Ⅰ vs CBT-n t = -4.794, P = 0.001). Basal ghrelin levels in BT- Ⅱ decreased more significantly than that in BT-Ⅰ group (t = 2.547, P = 0.029). Ghrelin levels expressed a downward trend after OGTT among obese children. The decrease in ghrelin levels at 60 min with respect to basal values was 56.9% in BT-Ⅰ. Ghrelin concentrations at 0 min correlated directly with glucose level at 0 min in BT-Ⅰ (r = 0.898, P = 0.015). There wasn't a significant correlation of ghrelin changes with glucose changes and insulin changes during OGTT in obese children with insulin resistance.CONCLUSION: In conclusion, in obese children with insulin resistance, ghrelin levels decreased with advancing pubertal stage. Ghrelin secretion suppression following OGTT was influenced by gender and pubertal stage. Baseline ghrelin levels and ghrelin suppression after OGTT did not significantly correlate with the degree of insulin resistance and insulin sensitivity.

  8. Proinsulin and Insulin Sensitivity as Predictors of Type 2 Diabetes Mellitus and Coronary Heart Disease : Clinical Epidemiological Studies with up to 27 Years of Follow-Up

    OpenAIRE

    Zethelius, Björn

    2002-01-01

    Defects in insulin secretion and insulin action are the major abnormalities in the development of Type 2 diabetes. Hyperinsulinemia is a risk marker for Type 2 diabetes and according to some, but not in all studies also for coronary heart disease (CHD). Conventional insulin assays measure immunoreactive insulin including proinsulin-like molecules. Proinsulin and insulin measured by specific methods, insulin sensitivity measured by the euglycemic insulin clamp and early insulin response after...

  9. Acute High-Intensity Interval Exercise-Induced Redox Signaling Is Associated with Enhanced Insulin Sensitivity in Obese Middle-Aged Men

    Science.gov (United States)

    Parker, Lewan; Stepto, Nigel K.; Shaw, Christopher S.; Serpiello, Fabio R.; Anderson, Mitchell; Hare, David L.; Levinger, Itamar

    2016-01-01

    Background: Obesity and aging are associated with increased oxidative stress, activation of stress and mitogen activated protein kinases (SAPK), and the development of insulin resistance and metabolic disease. In contrast, acute exercise also increases oxidative stress and SAPK signaling, yet is reported to enhance insulin sensitivity and reduce the risk of metabolic disease. This study explored this paradox by investigating the effect of a single session of high-intensity interval-exercise (HIIE) on redox status, muscle SAPK and insulin protein signaling in eleven middle-aged obese men. Methods: Participants completed a 2 h hyperinsulinaemic-euglycaemic clamp at rest, and 60 min after HIIE (4 × 4 mins at 95% HRpeak; 2 min recovery periods), separated by 1–3 weeks. Results: Irrespective of exercise-induced changes to redox status, insulin stimulation both at rest and after HIIE similarly increased plasma superoxide dismutase activity, plasma catalase activity, and skeletal muscle 4-HNE; and significantly decreased plasma TBARS and hydrogen peroxide. The SAPK signaling pathways of p38 MAPK, NF-κB p65, and JNK, and the distal insulin signaling protein AS160Ser588, were activated with insulin stimulation at rest and to a greater extent with insulin stimulation after a prior bout of HIIE. Higher insulin sensitivity after HIIE was associated with higher insulin-stimulated SOD activity, JNK, p38 MAPK and NF-κB phosphorylation (r = 0.63, r = 0.71, r = 0.72, r = 0.71; p < 0.05, respectively). Conclusion:These findings support a role for redox homeostasis and SAPK signaling in insulin-stimulated glucose uptake which may contribute to the enhancement of insulin sensitivity in obese men 3 h after HIIE.

  10. Determination of Insulin Secretory Defect and Insulin Sensitivity in Type 2 Diabetic Subjects in Bangladesh.

    Science.gov (United States)

    Ferdous, J; Ahmed, S; Laila, R; Islam, M T; Rahaman, M F; Snigdha, K R; Sarkar, S; Khan, A S; Sarkar, A K

    2016-01-01

    Diabetes mellitus (DM) is defined as a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. This study was undertaken to explore the basic defect in type 2 diabetes patients in Bangladesh. This was an observational study with case control design, was conducted in the Biomedical Research Group, Research Division, Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine Metabolic Disorders (BIRDEM), Dhaka, Bangladesh, during the period of July 2008 to June 2009. A total of 153 subjects were included in study of which 63 belonged to type 2 diabetes mellitus group and 90 were healthy controls. Fasting and 2 hours postprandial blood glucose, serum insulin, HOMA%B, HOMA%S, QuickI, Glucose /insulin ratio, TG were measured and age, BMI, WHR were recorded. Waist-hip ratio (WHR), was significantly higher in T2DM as compared to control subjects [WHR, mean±SD, 0.94±0.12 vs. 0.88±0.06, pBangladesh.

  11. Repeated prolonged whole-body low-intensity exercise: effects on insulin sensitivity and limb muscle adaptations

    DEFF Research Database (Denmark)

    Helge, Jørn Mikael; Overgaard, Kristian; Damsgaard, Rasmus;

    2006-01-01

    . Glycosylated hemoglobin (5.6% ± 0.01%) was not affected by the crossing. The IVGTT data revealed that insulin sensitivity (7.3 ± 0.6 mU · L-1 · min-1) and glucose effectiveness (0.024 ± 0.002 min-1) were not changed after the crossing. Similarly, the IVGTT data, when expressed per kilogram of lean body mass...

  12. MiR-155 Enhances Insulin Sensitivity by Coordinated Regulation of Multiple Genes in Mice

    Science.gov (United States)

    Lin, Taoyan; Lin, Xia; Chen, Li; Zeng, Hui; Han, Yanjiang; Wu, Lihong; Huang, Shun; Wang, Meng; Huang, Shenhao; Xie, Raoying; Liang, Liqi; Liu, Yu; Liu, Ruiyu; Zhang, Tingting; Li, Jing; Wang, Shengchun; Sun, Penghui; Huang, Wenhua; Yao, Kaitai; Xu, Kang; Du, Tao; Xiao, Dong

    2016-01-01

    miR-155 plays critical roles in numerous physiological and pathological processes, however, its function in the regulation of blood glucose homeostasis and insulin sensitivity and underlying mechanisms remain unknown. Here, we reveal that miR-155 levels are downregulated in serum from type 2 diabetes (T2D) patients, suggesting that miR-155 might be involved in blood glucose control and diabetes. Gain-of-function and loss-of-function studies in mice demonstrate that miR-155 has no effects on the pancreatic β-cell proliferation and function. Global transgenic overexpression of miR-155 in mice leads to hypoglycaemia, improved glucose tolerance and insulin sensitivity. Conversely, miR-155 deficiency in mice causes hyperglycemia, impaired glucose tolerance and insulin resistance. In addition, consistent with a positive regulatory role of miR-155 in glucose metabolism, miR-155 positively modulates glucose uptake in all cell types examined, while mice overexpressing miR-155 transgene show enhanced glycolysis, and insulin-stimulated AKT and IRS-1 phosphorylation in liver, adipose tissue or skeletal muscle. Furthermore, we reveal these aforementioned phenomena occur, at least partially, through miR-155-mediated repression of important negative regulators (i.e. C/EBPβ, HDAC4 and SOCS1) of insulin signaling. Taken together, these findings demonstrate, for the first time, that miR-155 is a positive regulator of insulin sensitivity with potential applications for diabetes treatment. PMID:27711113

  13. The insulin receptor activation process involves localized conformational changes.

    Science.gov (United States)

    Baron, V; Kaliman, P; Gautier, N; Van Obberghen, E

    1992-11-15

    The molecular process by which insulin binding to the receptor alpha-subunit induces activation of the receptor beta-subunit with ensuing substrate phosphorylation remains unclear. In this study, we aimed at approaching this molecular mechanism of signal transduction and at delineating the cytoplasmic domains implied in this process. To do this, we used antipeptide antibodies to the following sequences of the receptor beta-subunit: (i) positions 962-972 in the juxtamembrane domain, (ii) positions 1247-1261 at the end of the kinase domain, and (iii) positions 1294-1317 and (iv) positions 1309-1326, both in the receptor C terminus. We have previously shown that insulin binding to its receptor induces a conformational change in the beta-subunit C terminus. Here, we demonstrate that receptor autophosphorylation induces an additional conformational change. This process appears to be distinct from the one produced by ligand binding and can be detected in at least three different beta-subunit regions: the juxtamembrane domain, the kinase domain, and the C terminus. Hence, the cytoplasmic part of the receptor beta-subunit appears to undergo an extended conformational change upon autophosphorylation. By contrast, the insulin-induced change does not affect the juxtamembrane domain 962-972 nor the kinase domain 1247-1261 and may be limited to the receptor C terminus. Further, we show that the hormone-dependent conformational change is maintained in a kinase-deficient receptor due to a mutation at lysine 1018. Therefore, during receptor activation, the ligand-induced change could precede ATP binding and receptor autophosphorylation. We propose that insulin binding leads to a transient receptor form that may allow ATP binding and, subsequently, autophosphorylation. The second conformational change could unmask substrate-binding sites and stabilize the receptor in an active conformation. PMID:1331080

  14. Insulin sensitivity is reflected by characteristic metabolic fingerprints--a Fourier transform mass spectrometric non-targeted metabolomics approach.

    Directory of Open Access Journals (Sweden)

    Marianna Lucio

    Full Text Available BACKGROUND: A decline in body insulin sensitivity in apparently healthy individuals indicates a high risk to develop type 2 diabetes. Investigating the metabolic fingerprints of individuals with different whole body insulin sensitivity according to the formula of Matsuda, et al. (ISI(Matsuda by a non-targeted metabolomics approach we aimed a to figure out an unsuspicious and altered metabolic pattern, b to estimate a threshold related to these changes based on the ISI, and c to identify the metabolic pathways responsible for the discrimination of the two patterns. METHODOLOGY AND PRINCIPAL FINDINGS: By applying infusion ion cyclotron resonance Fourier transform mass spectrometry, we analyzed plasma of 46 non-diabetic subjects exhibiting high to low insulin sensitivities. The orthogonal partial least square model revealed a cluster of 28 individuals with alterations in their metabolic fingerprints associated with a decline in insulin sensitivity. This group could be separated from 18 subjects with an unsuspicious metabolite pattern. The orthogonal signal correction score scatter plot suggests a threshold of an ISI(Matsuda of 15 for the discrimination of these two groups. Of note, a potential subgroup represented by eight individuals (ISI(Matsuda value between 8.5 and 15 was identified in different models. This subgroup may indicate a metabolic transition state, since it is already located within the cluster of individuals with declined insulin sensitivity but the metabolic fingerprints still show some similarities with unaffected individuals (ISI >15. Moreover, the highest number of metabolite intensity differences between unsuspicious and altered metabolic fingerprints was detected in lipid metabolic pathways (arachidonic acid metabolism, metabolism of essential fatty acids and biosynthesis of unsaturated fatty acids, steroid hormone biosyntheses and bile acid metabolism, based on data evaluation using the metabolic annotation interface Mass

  15. Vitamin D intake is associated with insulin sensitivity in African American, but not European American, women

    Directory of Open Access Journals (Sweden)

    Oster Robert A

    2010-04-01

    Full Text Available Abstract Background The prevalence of type 2 diabetes is higher among African Americans (AA vs European Americans (EA, independent of obesity and other known confounders. Although the reason for this disparity is not known, it is possible that relatively low levels of vitamin D among AA may contribute, as vitamin D has been positively associated with insulin sensitivity in some studies. The objective of this study was to test the hypothesis that dietary vitamin D would be associated with a robust measure of insulin sensitivity in AA and EA women. Methods Subjects were 115 African American (AA and 137 European American (EA healthy, premenopausal women. Dietary intake was determined with 4-day food records; the insulin sensitivity index (SI with a frequently-sampled intravenous glucose tolerance test and minimal modeling; the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR with fasting insulin and glucose; and body composition with dual-energy X-ray absorptiometry. Results Vitamin D intake was positively associated with SI (standardized β = 0.18, P = 0.05 and inversely associated with HOMA-IR (standardized β = -0.26, P = 0.007 in AA, and the relationships were independent of age, total body fat, energy intake, and % kcal from fat. Vitamin D intake was not significantly associated with indices of insulin sensitivity/resistance in EA (standardized β = 0.03, P = 0.74 and standardized β = 0.02, P = 0.85 for SI and HOMA-IR, respectively. Similar to vitamin D, dietary calcium was associated with SI and HOMA-IR among AA but not EA. Conclusions This study provides novel findings that dietary vitamin D and calcium were independently associated with insulin sensitivity in AA, but not EA. Promotion of these nutrients in the diet may reduce health disparities in type 2 diabetes risk among AA, although longitudinal and intervention studies are required.

  16. 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.

  17. Effect of weight reduction on insulin sensitivity, sex hormone-binding globulin, sex hormones and gonadotrophins in obese children

    DEFF Research Database (Denmark)

    Birkebaek, N H; Lange, Aksel; Holland-Fischer, P;

    2010-01-01

    Obesity in men is associated with reduced insulin sensitivity and hypoandrogenism, while obesity in women is associated with reduced insulin sensitivity and hyperandrogenism. In children, the effect of obesity and weight reduction on the hypothalamo-pituitary-gonadal axis is rarely investigated. ....... The aim of the present study was to investigate the effect of weight reduction in obese Caucasian children on insulin sensitivity, sex hormone-binding globulin (SHBG), DHEAS and the hypothalamo-pituitary-gonadal axis....

  18. Long-term treatment with losartan versus atenolol improves insulin sensitivity in hypertension: ICARUS, a LIFE substudy

    DEFF Research Database (Denmark)

    Olsen, Michael H; Fossum, Eigil; Høieggen, Aud;

    2005-01-01

    Hypertension and insulin resistance might be associated through peripheral vascular hypertrophy/rarefaction which compromises skeletal muscle blood flow and decreases glucose uptake, inducing insulin resistance. We hypothesized that treatment with losartan as compared to atenolol would improve...... insulin sensitivity through regression of peripheral vascular hypertrophy/rarefaction....

  19. Exercise training augments the peripheral insulin-sensitizing effects of pioglitazone in HIV-infected adults with insulin resistance and central adiposity

    OpenAIRE

    Yarasheski, Kevin E.; Cade, W. Todd; Overton, E Turner; Mondy, Kristin E.; HUBERT, Sara; Laciny, Erin; Bopp, Coco; Lassa-Claxton, Sherry; Reeds, Dominic N.

    2010-01-01

    The prevalence and incidence of insulin resistance and type 2 diabetes mellitus (DM) are higher in people treated for human immunodeficiency virus-1 (HIV) infection than in the general population. Identifying safe and effective interventions is a high priority. We evaluated whether the peroxisome proliferator-activated receptor-γ agonist pioglitazone with exercise training improves central and peripheral insulin sensitivity more than pioglitazone alone in HIV-infected adults with insulin resi...

  20. How does acupuncture affect insulin sensitivity in women with polycystic ovary syndrome and insulin resistance? Study protocol of a prospective pilot study

    OpenAIRE

    Zheng, Yanhua; Stener-Victorin, Elisabet; Ng, Ernest H. Y.; Li, Juan; Wu, Xiaoke; Ma, Hongxia

    2015-01-01

    Introduction Hyperinsulinaemia and insulin resistance (IR) are key features of polycystic ovary syndrome (PCOS) and metabolic syndrome. The effect of 5 weeks of acupuncture treatment has been investigated in a completed prospective pilot trial (Clinicaltrials.gov: NCT01457209), and acupuncture with electrical stimulation applied to insulin-resistant rats with dihydrotestosterone-induced PCOS was shown to improve insulin sensitivity. Therefore, we now aim to conduct a prospective pilot study t...

  1. Surgical removal of visceral fat decreases plasma free fatty acid and increases insulin sensitivity on liver and peripheral tissue in monosodium glutamate (MSG)-obese rats.

    Science.gov (United States)

    Kim, Y W; Kim, J Y; Lee, S K

    1999-10-01

    In order to evaluate the role of visceral and subcutaneous fat tissue in insulin sensitivity and lipid metabolism, we measured the fasting levels of plasma free fatty acid (FFA) and insulin, glucose disappearance rate (Rd), and hepatic glucose production rate (HGP) after surgical removal of visceral (VF) or subcutaneous (SF) fat tissue in monosodium glutamate-obese (MSG-Ob) rats. Monosodium glutamate obesity was induced in rats by neonatal injection of MSG. Surgery to remove fat was done at 15 weeks of age. The experiments were done four weeks after the surgery. MSG-Ob rats showed increased levels of FFA, insulin, and HGP and decreased Rd compared to normal rats. In the VF group, the FFA level and HGP were decreased to normal values, Rd was partially normalized, but the level of insulin did not change significantly compared to MSG-Ob. In the SF group, FFA and Rd were partially normalized, but HGP was not suppressed significantly compared to MSG-Ob. These results suggest that visceral fat affects the insulin sensitivity of liver and FFA concentration more than subcutaneous fat; however, no significant difference was shown on whole body insulin sensitivity and fasting insulin concentration. PMID:10576150

  2. pH-Sensitive oral insulin delivery systems using Eudragit microspheres.

    Science.gov (United States)

    Mundargi, Raghavendra C; Rangaswamy, Vidhya; Aminabhavi, Tejraj M

    2011-08-01

    In this paper, we present in vitro and in vivo release data on pH-sensitive microspheres of Eudragit L100, Eudragit RS100 and their blend systems prepared by double emulsion-solvent evaporation technique for oral delivery of insulin. Of the three systems developed, Eudragit L100 was chosen for preclinical studies. Insulin was encapsulated and in vitro experiments performed on insulin-loaded microspheres in pH 1.2 media did not release insulin during the first 2 h, but maximum insulin was released in pH 7.4 buffer media from 4 to 6 h. The microspheres were characterized by scanning electron microscopy to understand particle size, shape and surface morphology. The size of microspheres ranged between 1 and 40 μm. Circular dichroism spectra indicated the structural integrity of insulin during encapsulation as well as after its release in pH 7.4 buffer media. The in vivo release studies on diabetic-induced rat models exhibited maximum inhibition of up to 86%, suggesting absorption of insulin in the intestine.

  3. Modulation of Insulin Sensitivity of Hepatocytes by the Pharmacological Downregulation of Phospholipase D

    Directory of Open Access Journals (Sweden)

    Nataliya A. Babenko

    2015-01-01

    Full Text Available Background. The role of phospholipase D (PLD as a positive modulator of glucose uptake activation by insulin in muscle and adipose cells has been demonstrated. The role of PLD in the regulation of glucose metabolism by insulin in the primary hepatocytes has been determined in this study. Methods. For this purpose, we studied effects of inhibitors of PLD on glucose uptake and glycogen synthesis stimulation by insulin. To determine the PLD activity, the method based on determination of products of transphosphatidylation reaction, phosphatidylethanol or phosphatidylbutanol, was used. Results. Inhibition of PLD by a general antagonist (1-butanol or specific inhibitor, halopemide, or N-hexanoylsphingosine, or by cellular ceramides accumulated in doxorubicin-treated hepatocytes decreased insulin-stimulated glucose metabolism. Doxorubicin-induced hepatocytes resistance to insulin action could be abolished by inhibition of ceramide production. Halopemide could nullify this effect. Addition of propranolol, as well as inhibitors of phosphatidylinositol 3-kinase (PI3-kinase (wortmannin, LY294002 or suppressors of Akt phosphorylation/activity, luteolin-7-O-glucoside or apigenin-7-O-glucoside, to the culture media could block cell response to insulin action. Conclusion. PLD plays an important role in the insulin signaling in the hepatocytes. PLD is activated downstream of PI3-kinase and Akt and is highly sensitive to ceramide content in the liver cells.

  4. Infection with Soil-Transmitted Helminths Is Associated with Increased Insulin Sensitivity.

    Directory of Open Access Journals (Sweden)

    Aprilianto E Wiria

    Full Text Available Given that helminth infections have been shown to improve insulin sensitivity in animal studies, which may be explained by beneficial effects on energy balance or by a shift in the immune system to an anti-inflammatory profile, we investigated whether soil-transmitted helminth (STH-infected subjects are more insulin sensitive than STH-uninfected subjects.We performed a cross-sectional study on Flores island, Indonesia, an area with high prevalence of STH infections.From 646 adults, stool samples were screened for Trichuris trichiura by microscopy and for Ascaris lumbricoides, Necator americanus, Ancylostoma duodenale, and Strongyloides stercoralis by qPCR. No other helminth was found. We collected data on body mass index (BMI, kg/m2, waist-to-hip ratio (WHR, fasting blood glucose (FBG, mmol/L, insulin (pmol/L, high sensitive C-reactive protein (ng/ml and Immunoglobulin E (IU/ml. The homeostatic model assessment for insulin resistance (HOMAIR was calculated and regression models were used to assess the association between STH infection status and insulin resistance.424 (66% participants had at least one STH infection. STH infected participants had lower BMI (23.2 vs 22.5 kg/m2, p value = 0.03 and lower HOMAIR (0.97 vs 0.81, p value = 0.05. In an age-, sex- and BMI-adjusted model a significant association was seen between the number of infections and HOMAIR: for every additional infection with STH species, the HOMAIR decreased by 0.10 (p for linear trend 0.01. This effect was mainly accounted for by a decrease in insulin of 4.9 pmol/L for every infection (p for trend = 0.07.STH infections are associated with a modest improvement of insulin sensitivity, which is not accounted for by STH effects on BMI alone.

  5. Glucose homeostasis and insulin sensitivity in growth hormone-transgenic mice: a cross-sectional analysis.

    Science.gov (United States)

    Boparai, Ravneet K; Arum, Oge; Khardori, Romesh; Bartke, Andrzej

    2010-10-01

    In contrast to its stimulatory effects on musculature, bone, and organ development, and its lipolytic effects, growth hormone (GH) opposes insulin effects on glucose metabolism. Chronic GH overexposure is thought to result in insulin insensitivity and decreased blood glucose homeostatic control. Yet, despite the importance of this concept for basic biology, as well as human conditions of GH excess or deficiency, no systematic assessment of the impact of GH over- expression on glucose homeostasis and insulin sensitivity has been conducted. We report that male and female adult GH transgenic mice have enhanced glucose tolerance compared to littermate controls and this effect is not dependent on age or on the particular heterologous GH transgene used. Furthermore, increased glucose-stimulated insulin secretion, augmented insulin sensitivity, and muted gluconeogenesis were also observed in bovine GH overexpressing mice. These results show that markedly increased systemic GH concentration in GH-transgenic mice exerts unexpected beneficial effects on glucose homeostasis, presumably via a compensatory increase in insulin release. The counterintuitive nature of these results challenges previously held presumptions of the physiology of these mice and other states of GH overexpression or suppression. In addition, they pose intriguing queries about the relationships between GH, endocrine control of metabolism, and aging. PMID:20707609

  6. Nickel nanoparticle-modified electrode for ultra-sensitive electrochemical detection of insulin.

    Science.gov (United States)

    Yu, Yanan; Guo, Meisong; Yuan, Mengwei; Liu, Weitong; Hu, Jingbo

    2016-03-15

    An ultra-sensitive electrochemical sensor for the detection of insulin was fabricated, using low-cost and environmentally friendly nickel nanoparticles (NiNPs) by ion implantation. The morphology and structure of the NiNPs are characterized by scanning electron microscopy (SEM), revealing diameters ranging from 4 to 8 nm. The insulin assay performances were evaluated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and chronoamperometry (I-t). The NiNPs-modified indium tin oxide electrode (NiNPs/ITO) showed excellent analytical features, including ultra-high sensitivity (2140 μAμM(-1)) for detecting low concentrations of insulin, an incredibly low detection limit (10 pM) and a wide dynamic range (100 pM to 2400 pM and 1 nM to 125 nM). In addition, the NiNPs/ITO electrode was also used to analyze the insulin concentration in bovine insulin injections. The NiNPs/ITO electrode is expected to be used as a potential biosensor for insulin.

  7. Differentiation of the insulin-sensitive glucose transporter in 3T3-L1 adipocytes

    International Nuclear Information System (INIS)

    3T3-L1 fibroblasts differentiate in culture to resemble adipocytes both morphologically and biochemically. Insulin-sensitive glucose transport, as measured by 2-deoxy-[1-14C]- glucose uptake in the undifferentiated cell is small (2X). In contrast, the rate of glucose transport in fully differentiated cells is elevated 15-fold over basal in the presence of insulin. To determine if this is due to an increase in the number of transporters/cell or accessibility to the transporters, the number of transporters was measured in subcellular fractions over differentiation using a 3H-cytochalasin B binding assay. The increase in the rate of insulin-sensitive glucose transport directly parallels an increase in the number of transporters which reside in an insulin-responsive intracellular compartment. This observation was confirmed by identifying the transporters by immunoblotting using an antibody generated against the human erythrocyte transporter. The molecular weight of this transporter increases over differentiation from a single band of 40kDa to a heterogeneous triplet of 40, 44 and 48kDa. These data suggest that the transporter undergoes differential processing and that the functional, insulin-responsive transporter may be different from the insulin-insensitive (basal) transporter

  8. Stimulatory effect of insulin on glucose uptake by muscle involves the central nervous system in insulin-sensitive mice

    NARCIS (Netherlands)

    Coomans, C.P.; Biermasz, N.R.; Geerling, J.J.; Guigas, B.; Rensen, P.C.N.; Havekes, L.M.; Romijn, J.A.

    2011-01-01

    OBJECTIVE - Insulin inhibits endogenous glucose production (EGP) and stimulates glucose uptake in peripheral tissues. Hypothalamic insulin signaling is required for the inhibitory effects of insulin on EGP. We examined the contribution of central insulin signaling on circulating insulin-stimulated t

  9. Early Clinical Detection of Pharmacologic Response in Insulin Action in a Nondiabetic Insulin-Resistant Population

    Directory of Open Access Journals (Sweden)

    Sudha S. Shankar, MD

    2015-12-01

    Conclusions: Significant changes in insulin action across multiple insulin-sensitive tissues can be detected within 2 weeks of initiation of insulin-sensitizing therapy with pioglitazone in obese patients with nondiabetic insulin resistance. ClinicalTrials.gov identifier: NCT01115712.

  10. Early enhancements of hepatic and later of peripheral insulin sensitivity combined with increased postprandial insulin secretion contribute to improved glycemic control after Roux-en-Y gastric bypass

    DEFF Research Database (Denmark)

    Bojsen-Møller, Kirstine N; Dirksen, Carsten; Jørgensen, Nils Bruun;

    2014-01-01

    to an intravenous glucose-glucagon challenge as well as an oral glucose load. Already within 1 week, RYGB reduced basal glucose production, improved basal hepatic insulin sensitivity and increased insulin clearance highlighting the liver as an important organ responsible for the early effects on glucose metabolism...

  11. Developmental Programming: Impact of Gestational Steroid and Metabolic Milieus on Adiposity and Insulin Sensitivity in Prenatal Testosterone-Treated Female Sheep.

    Science.gov (United States)

    Cardoso, Rodolfo C; Veiga-Lopez, Almudena; Moeller, Jacob; Beckett, Evan; Pease, Anthony; Keller, Erica; Madrigal, Vanessa; Chazenbalk, Gregorio; Dumesic, Daniel; Padmanabhan, Vasantha

    2016-02-01

    Prenatally testosterone (T)-treated sheep present metabolic disruptions similar to those seen in women with polycystic ovary syndrome. These females exhibit an increased ratio of small to large adipocytes, which may be the earliest event in the development of adult insulin resistance. Additionally, our longitudinal studies suggest the existence of a period of compensatory adaptation during development. This study tested whether 1) in utero cotreatment of prenatally T-treated sheep with androgen antagonist (flutamide) or insulin sensitizer (rosiglitazone) prevents juvenile insulin resistance and adult changes in adipocyte size; and 2) visceral adiposity and insulin sensitivity are both unaltered during early adulthood, confirming the predicted developmental trajectory in this animal model. Insulin sensitivity was tested during juvenile development and adipose tissue distribution, adipocyte size, and concentrations of adipokines were determined during early adulthood. Prenatal T-treated females manifested juvenile insulin resistance, which was prevented by prenatal rosiglitazone cotreatment. Neither visceral adiposity nor insulin sensitivity differed between groups during early adulthood. Prenatal T-treated sheep presented an increase in the relative proportion of small adipocytes, which was not substantially prevented by either prenatal intervention. A large effect size was observed for increased leptin concentrations in prenatal T-treated sheep compared with controls, which was prevented by prenatal rosiglitazone. In conclusion, gestational alterations in insulin-glucose homeostasis likely play a role in programming insulin resistance, but not adipocyte size distribution, in prenatal T-treated sheep. Furthermore, these results support the notion that a period of compensatory adaptation of the metabolic system to prenatal T exposure occurs between puberty and adulthood. PMID:26650569

  12. Insulin sensitivity in type 2 diabetes is closely associated with LDL particle size

    OpenAIRE

    Krayenbuehl, P A; Wiesli, P; Schmid, C.; Lehmann, R.; Spinas, G A; Berneis, K.

    2008-01-01

    PRINCIPLES: Small dense LDLs have been found to be associated with type 2 diabetes (T2DM). This association has been observed in the context of decreased HDL cholesterol and increased triglycerides. METHODS: In the present study the relationship between LDL particle size and insulin sensitivity was assessed in 46 patients with T2DM (mean age 60 (11) years, HbA1c 7.6 (0.8) %). 75 g oral glucose tolerance testing was performed and composite insulin sensitivity index was calculated by the method...

  13. Partial disruption of lipolysis increases postexercise insulin sensitivity in skeletal muscle despite accumulation of DAG

    DEFF Research Database (Denmark)

    Serup, Annette Karen Lundbeck; Alsted, Thomas Junker; Jordy, Andreas Børsting;

    2016-01-01

    reactivity in vitro, we investigated if the described function of DAGs as mediators of lipid-induced insulin resistance was depending on the different DAG-isomers. We measured insulin stimulated glucose uptake in hormone sensitive lipase (HSL) knock out (KO) mice after treadmill exercise to stimulate...... accumulation of DAGs in skeletal muscle. We found that despite an increased DAG content in muscle after exercise in HSL KO mice, the HSL KO mice showed a higher insulin stimulated glucose uptake post exercise compared to wildtype. Further analysis of the chemical structure and cellular localization of DAG...... in skeletal muscle revealed that HSL KO mice accumulated sn-1,3 DAG and not sn-1,2 DAG. Accordingly, these results highlight the importance of taking the chemical structure and cellular localization of DAG into account when evaluating the role of DAG in lipid induced insulin resistance in skeletal muscle...

  14. Hormone-sensitive lipase deficiency suppresses insulin secretion from pancreatic islets of Lepob/ob mice

    International Nuclear Information System (INIS)

    It has long been a matter of debate whether the hormone-sensitive lipase (HSL)-mediated lipolysis in pancreatic β-cells can affect insulin secretion through the alteration of lipotoxicity. We generated mice lacking both leptin and HSL (Lepob/ob/HSL-/-) and explored the role of HSL in pancreatic β-cells in the setting of obesity. Lepob/ob/HSL-/- developed elevated blood glucose levels and reduced plasma insulin levels compared with Lepob/ob/HSL+/+ in a fed state, while the deficiency of HSL did not affect glucose homeostasis in Lep+/+ background. The deficiency of HSL exacerbated the accumulation of triglycerides in Lepob/ob islets, leading to reduced glucose-stimulated insulin secretion. The deficiency of HSL also diminished the islet mass in Lepob/ob mice due to decreased cell proliferation. In conclusion, HSL affects insulin secretary capacity especially in the setting of obesity.

  15. Adipose Triglyceride Lipase Deficiency Causes Tissue-specific Changes in Insulin Signaling*

    OpenAIRE

    Kienesberger, Petra C.; Lee, Daeho; Pulinilkunnil, Thomas; Brenner, Daniel S.; Cai, Lingzhi; Magnes, Christoph; Koefeler, Harald C.; Streith, Ingo E.; Rechberger, Gerald N.; Haemmerle, Guenter; Flier, Jeffrey S.; Zechner, Rudolf; Kim, Young-Bum; Kershaw, Erin E.

    2009-01-01

    Triacylglycerol accumulation in insulin target tissues is associated with insulin resistance. Paradoxically, mice with global targeted deletion of adipose triglyceride lipase (ATGL), the rate-limiting enzyme in triacylglycerol hydrolysis, display improved glucose tolerance and insulin sensitivity despite triacylglycerol accumulation in multiple tissues. To determine the molecular mechanisms for this phenotype, ATGL-deficient (ATGL−/−) and wild-type mice were injected with saline or insulin (1...

  16. Chronic hyperinsulinemia reduces insulin sensitivity and metabolic functions of brown adipocyte.

    Science.gov (United States)

    Rajan, Sujith; Shankar, Kripa; Beg, Muheeb; Varshney, Salil; Gupta, Abhishek; Srivastava, Ankita; Kumar, Durgesh; Mishra, Raj K; Hussain, Zakir; Gayen, Jiaur R; Gaikwad, Anil N

    2016-09-01

    The growing pandemics of diabetes have become a real threat to world economy. Hyperinsulinemia and insulin resistance are closely associated with the pathophysiology of type 2 diabetes. In pretext of brown adipocytes being considered as the therapeutic strategy for the treatment of obesity and insulin resistance, we have tried to understand the effect of hyperinsulinemia on brown adipocyte function. We here with for the first time report that hyperinsulinemia-induced insulin resistance in brown adipocyte is also accompanied with reduced insulin sensitivity and brown adipocyte characteristics. CI treatment decreased expression of brown adipocyte-specific markers (such as PRDM16, PGC1α, and UCP1) and mitochondrial content as well as activity. CI-treated brown adipocytes showed drastic decrease in oxygen consumption rate (OCR) and spare respiratory capacity. Morphological study indicates increased accumulation of lipid droplets in CI-treated brown adipocytes. We have further validated these findings in vivo in C57BL/6 mice implanted with mini-osmotic insulin pump for 8weeks. CI treatment in mice leads to increased body weight gain, fat mass and impaired glucose intolerance with reduced energy expenditure and insulin sensitivity. CI-treated mice showed decreased BAT characteristics and function. We also observed increased inflammation and ER stress markers in BAT of CI-treated animals. The above results conclude that hyperinsulinemia has deleterious effect on brown adipocyte function, making it susceptible to insulin resistance. Thus, the above findings have greater implication in designing approaches for the treatment of insulin resistance and diabetes via recruitment of brown adipocytes. PMID:27340034

  17. Association of oxidative status and insulin sensitivity in periparturient dairy cattle: an observational study.

    Science.gov (United States)

    Abuelo, A; Hernández, J; Benedito, J L; Castillo, C

    2016-04-01

    Post-parturient insulin resistance (IR) is a common feature in all mammalian animals. However, in dairy cows, it can be exacerbated because of high milk yield, leading to excessive negative energy balance, which is related with increased disease incidence, reduced milk production and worsened reproductive performance. IR has been extensively investigated in humans suffering from diabetes mellitus. In these subjects, it is known that oxidative stress (OS) plays a causative role in the onset of IR. Although OS occurs in transitional dairy cattle, there are yet no studies that investigated the association between IR and OS in dairy cattle. Therefore, the aim of this study was to investigate whether there is a relationship between OS and IR in dairy cattle. Serum samples were taken repeatedly from 22 dairy cows from 2 months prior to the expected calving date to 2 months after calving and were analysed for markers of metabolic and redox balance. Surrogate indices of insulin sensitivity were also calculated. Generalised linear mixed models revealed an effect of the oxidative status on peripheral insulin concentration and on indices of insulin sensitivity. Hence, field trials should investigate the effectiveness of antioxidant therapy on insulin sensitivity in peripheral tissues during the transition period of dairy cattle.

  18. Vasopeptidase inhibition improves insulin sensitivity and endothelial function in the JCR:LA-cp rat.

    Science.gov (United States)

    Russell, James C; Kelly, Sandra E; Schäfer, Stefan

    2004-08-01

    The insulin-resistant, hyperinsulinemic, normoglycemic, and obese JCR:LA-cp rat was used to study the effects of ramipril (an ACE inhibitor) and AVE7688 (a dual inhibitor of ACE and neutral endopeptidases) on insulin sensitivity and vascular function. Both compounds reduced the surge of plasma insulin in a meal tolerance test by approximately 50%. Ramipril had no effect on acetylcholine-induced relaxation but increased the sensitivity to sodium nitroprus-side at low concentrations. AVE7688 significantly reduced the EC50 for acetylcholine to relax phenylephrine-contracted aortic rings. None of the compounds affected the baseline coronary flow and reactive hyperemia. Coronary flow response to bradykinin in AVE7688- and ramipril-treated rat hearts showed a significantly lower EC50 than in control rats. Maximum flow rate was not different between groups. In summary, both ramipril and AVE7688 had significant hypoinsulinemic and insulin-sensitizing effects. Whereas ramipril had limited vascular effects, AVE7688 had more marked beneficial vascular effects, probably of endothelial origin and possibly related to lowered insulin levels.

  19. Insulin sensitivity and complications in type 1 diabetes:New insights

    Institute of Scientific and Technical Information of China (English)

    Petter Bjornstad; Janet K Snell-Bergeon; Kristen J Nadeau; David M Maahs

    2015-01-01

    Despite improvements in glucose, lipids and bloodpressure control, vascular complications remain themost important cause of morbidity and mortality inpatients with type 1 diabetes. For that reason, there is aneed to identify additional risk factors to utilize in clinicalpractice or translate to novel therapies to preventvascular complications. Reduced insulin sensitivityis an increasingly recognized component of type 1diabetes that has been linked with the developmentand progression of both micro- and macrovascularcomplications. Adolescents and adults with type 1diabetes have reduced insulin sensitivity, even whencompared to their non-diabetic counterparts of similaradiposity, serum triglycerides, high-density lipoproteincholesterol, level of habitual physical activity, and inadolescents, pubertal stage. Reduced insulin sensitivityis thought to contribute both to the initiation andprogression of macro- and microvascular complicationsin type 1 diabetes. There are currently clinical trialsunderway examining the benefits of improving insulinsensitivity with regards to vascular complications in type1 diabetes. Reduced insulin sensitivity is an increasinglyrecognized component of type 1 diabetes, is implicatedin the pathogenesis of vascular complications and ispotentially an important therapeutic target to preventvascular complications. In this review, we will focus onthe pathophysiologic contribution of insulin sensitivity tovascular complications and summarize related ongoingclinical trials.

  20. Association of oxidative status and insulin sensitivity in periparturient dairy cattle: an observational study.

    Science.gov (United States)

    Abuelo, A; Hernández, J; Benedito, J L; Castillo, C

    2016-04-01

    Post-parturient insulin resistance (IR) is a common feature in all mammalian animals. However, in dairy cows, it can be exacerbated because of high milk yield, leading to excessive negative energy balance, which is related with increased disease incidence, reduced milk production and worsened reproductive performance. IR has been extensively investigated in humans suffering from diabetes mellitus. In these subjects, it is known that oxidative stress (OS) plays a causative role in the onset of IR. Although OS occurs in transitional dairy cattle, there are yet no studies that investigated the association between IR and OS in dairy cattle. Therefore, the aim of this study was to investigate whether there is a relationship between OS and IR in dairy cattle. Serum samples were taken repeatedly from 22 dairy cows from 2 months prior to the expected calving date to 2 months after calving and were analysed for markers of metabolic and redox balance. Surrogate indices of insulin sensitivity were also calculated. Generalised linear mixed models revealed an effect of the oxidative status on peripheral insulin concentration and on indices of insulin sensitivity. Hence, field trials should investigate the effectiveness of antioxidant therapy on insulin sensitivity in peripheral tissues during the transition period of dairy cattle. PMID:26174108

  1. The relationship between heat shock protein 72 expression in skeletal muscle and insulin sensitivity is dependent on adiposity

    DEFF Research Database (Denmark)

    Henstridge, Darren C; Forbes, Josephine M; Penfold, Sally A;

    2010-01-01

    Decreased gene expression of heat shock protein 72 (HSP72) in skeletal muscle is associated with insulin resistance in humans. We aimed to determine whether HSP72 protein expression in insulin-sensitive tissues is related to criterion standard measures of adiposity and insulin resistance in a young...... insulin sensitivity. Skeletal muscle and subcutaneous adipose tissue biopsies were obtained by percutaneous needle biopsy. HSP72 protein expression in skeletal muscle was inversely related to percentage body fat (r = -0.54, P <.05) and remained significant after adjustment for age and sex (P <.05......). Insulin sensitivity was also related to HSP72 protein expression in skeletal muscle (r = 0.52, P <.05); however, this relationship disappeared after adjustment for percentage body fat (P = .2). In adipose tissue, HSP72 protein expression was not related to adiposity or insulin sensitivity. Physical...

  2. Acute effects of 17 β-estradiol and genistein on insulin sensitivity and spatial memory in aged ovariectomized female rats.

    Science.gov (United States)

    Alonso, Ana; González-Pardo, Héctor; Garrido, Pablo; Conejo, Nélida M; Llaneza, Plácido; Díaz, Fernando; Del Rey, Carmen González; González, Celestino

    2010-12-01

    Aging is characterized by decline in metabolic function and insulin resistance, and both seem to be in the basis of neurodegenerative diseases and cognitive dysfunction. Estrogens prevent age-related changes, and phytoestrogens influence learning and memory. Our hypothesis was that estradiol and genistein, using rapid-action mechanisms, are able to modify insulin sensitivity, process of learning, and spatial memory. Young and aged ovariectomized rats received acute treatment with estradiol or genistein. Aged animals were more insulin-resistant than young. In each age, estradiol and genistein-treated animals were less insulin-resistant than the others, except in the case of young animals treated with high doses of genistein. In aged rats, no differences between groups were found in spatial memory test, showing a poor performance in the water maze task. However, young females treated with estradiol or high doses of genistein performed well in spatial memory task like the control group. Only rats treated with high doses of genistein showed an optimal spatial memory similar to the control group. Conversely, acute treatment with high doses of phytoestrogens improved spatial memory consolidation only in young rats, supporting the critical period hypothesis for the beneficial effects of estrogens on memory. Therefore, genistein treatment seems to be suitable treatment in aged rats in order to prevent insulin resistance but not memory decline associated with aging. Acute genistein treatment is not effective to restore insulin resistance associated to the early loss of ovarian function, although it can be useful to improve memory deficits in this condition. PMID:20467821

  3. A low-fat Diet improves insulin sensitivity in patients with type 1 diabetes

    DEFF Research Database (Denmark)

    Rosenfalck, AM; Almdal, Thomas Peter; Viggers, Lone;

    2006-01-01

    diet (P = 0.039). The daily protein and carbohydrate intake increased (+4.4% of total energy intake, P = 0.0049 and +2.5%, P = 0.34, respectively), while alcohol intake decreased (-3.2% of total energy intake, P = 0.02). There was a significant improvement in insulin sensitivity on the isocaloric, low......AIMS: To compare the effects on insulin sensitivity, body composition and glycaemic control of the recommended standard weight-maintaining diabetes diet and an isocaloric low-fat diabetes diet during two, 3-month periods in patients with Type 1 diabetes. METHODS: Thirteen Type 1 patients were...... by the insulin clamp technique at baseline and after each of the diet intervention periods. RESULTS: On an isocaloric low-fat diet, Type 1 diabetic patients significantly reduced the proportion of fat in the total daily energy intake by 12.1% (or -3.6% of total energy) as compared with a conventional diabetes...

  4. Weight-loss changes PPAR expression, reduces atherosclerosis and improves cardiovascular function in obese insulin-resistant mice

    Energy Technology Data Exchange (ETDEWEB)

    Verreth, Wim; Verhamme, Peter; Pelat, Michael; Ganame, Javier; Bielicki, John K.; Mertens, Ann; Quarck, Rozenn; Benhabiles, Nora; Marguerie, Gerard; Mackness, Bharti; Mackness, Mike; Ninio, Ewa; Herregods, Marie-Christine; Balligand, Jean-Luc; Holvoet, Paul

    2003-09-01

    Weight-loss in obese insulin-resistant, but not in insulin-sensitive, persons reduces CHD risk. It is not known to what extent changes in the adipose gene expression profile are important for reducing CHD risk. We studied the effect of diet restriction-induced weight-loss on gene expression in adipose tissue, atherosclerosis and cardiovascular function in mice with combined leptin and LDL-receptor deficiency. Obesity, hypertriglyceridemia and insulin-resistance are associated with hypertension, impaired left ventricle function and accelerated atherosclerosis in those mice. Diet restriction during 12 weeks caused a 45% weight-loss and changes in the gene expression in adipose tissue of PPARa and PPAR? and of key genes regulating glucose transport and insulin sensitivity, lipid metabolism, oxidative stress and inflammation, most of which are under the transcriptional control of PPARs. These changes were associated with increased insulin-sensitivity, decreased hypertriglyceridemia, reduced mean 24-hour blood pressure and heart rate, restored circadian variations of blood pressure and heart rate, increased ejection fraction, and reduced atherosclerosis. Thus, induction of PPARa and PPAR? in adipose tissue is a key mechanism for reducing atherosclerosis and improving cardiovascular function resulting from weight-loss. Our observations point to the critical role of PPARs in the pathogenesis of cardiovascular features of the metabolic syndrome.

  5. Strength Exercise Improves Muscle Mass and Hepatic Insulin Sensitivity in Obese Youth

    NARCIS (Netherlands)

    Van Der Heijden, Gert-Jan; Wang, Zhiyue J.; Chu, Zili; Toffolo, Gianna; Manesso, Erica; Sauer, Pieter J. J.; Sunehag, Agneta L.

    2010-01-01

    VAN DER HEIJDEN, G.-J., Z. J. WANG, Z. CHU, G. TOFFOLO, E. MANESSO, P. J. J. SAUER, and A. L. SUNEHAG. Strength Exercise Improves Muscle Mass and Hepatic Insulin Sensitivity in Obese Youth. Med. Sci. Sports Exerc., Vol. 42, No. 11, pp. 1973-1980, 2010. Introduction: Data on the metabolic effects of

  6. PUFAs acutely affect triacylglycerol-derived skeletal muscle fatty acid uptake and increase postprandial insulin sensitivity

    NARCIS (Netherlands)

    Jans, A.; Konings, E.; Goossens, G.H.; Bouwman, F.G.; Moors, C.C.; Boekschoten, M.V.; Afman, L.A.; Muller, M.R.; Mariman, E.C.; Blaak, E.E.

    2012-01-01

    Background: Dietary fat quality may influence skeletal muscle lipid processing and fat accumulation, thereby modulating insulin sensitivity. Objective: The objective was to examine the acute effects of meals with various fatty acid (FA) compositions on skeletal muscle FA processing and postprandial

  7. Moderate alcohol consumption increases insulin sensitivity and ADIPOQ expression in postmenopausal women: A randomised, crossover trial

    NARCIS (Netherlands)

    Joosten, M.M.; Beulens, J.W.J.; Kersten, S.; Hendriks, H.F.J.

    2008-01-01

    Aims/hypothesis: To determine whether 6 weeks of daily, moderate alcohol consumption increases expression of the gene encoding adiponectin (ADIPOQ) and plasma levels of the protein, and improves insulin sensitivity in postmenopausal women. Methods: In a randomised, open-label, crossover trial conduc

  8. Enhanced insulin sensitivity in skeletal muscle and liver by physiological overexpression of SIRT6

    Directory of Open Access Journals (Sweden)

    Jason G. Anderson

    2015-11-01

    Conclusions: Our data indicate that moderate, physiological overexpression of SIRT6 enhances insulin sensitivity in skeletal muscle and liver, engendering protective actions against diet-induced T2DM. Hence, the present study provides support for the anti-T2DM effect of SIRT6 and suggests SIRT6 as a putative molecular target for anti-T2DM treatment.

  9. Infection with Soil-Transmitted Helminths Is Associated with Increased Insulin Sensitivity

    NARCIS (Netherlands)

    Wiria, A.E.; Hamid, F.; Wammes, L.J.; Prasetyani, M.A.; Dekkers, O.M.; May, L.; Kaisar, M.M.; Verweij, J.J.; Guigas, B.; Partono, F.; Sartono, E.; Supali, T.; Yazdanbakhsh, M.; Smit, J.W.A.

    2015-01-01

    OBJECTIVE: Given that helminth infections have been shown to improve insulin sensitivity in animal studies, which may be explained by beneficial effects on energy balance or by a shift in the immune system to an anti-inflammatory profile, we investigated whether soil-transmitted helminth (STH)-infec

  10. Saffron (Crocus sativus L.) increases glucose uptake and insulin sensitivity in muscle cells via multipathway mechanisms.

    Science.gov (United States)

    Kang, Changkeun; Lee, Hyunkyoung; Jung, Eun-Sun; Seyedian, Ramin; Jo, MiNa; Kim, Jehein; Kim, Jong-Shu; Kim, Euikyung

    2012-12-15

    Saffron (Crocus sativus Linn.) has been an important subject of research in the past two decades because of its various biological properties, including anti-cancer, anti-inflammatory, and anti-atherosclerotic activities. On the other hand, the molecular bases of its actions have been scarcely understood. Here, we elucidated the mechanism of the hypoglycemic actions of saffron through investigating its signaling pathways associated with glucose metabolism in C(2)C(12) skeletal muscle cells. Saffron strongly enhanced glucose uptake and the phosphorylation of AMPK (AMP-activated protein kinase)/ACC (acetyl-CoA carboxylase) and MAPKs (mitogen-activated protein kinases), but not PI 3-kinase (Phosphatidylinositol 3-kinase)/Akt. Interestingly, the co-treatment of saffron and insulin further improved the insulin sensitivity via both insulin-independent (AMPK/ACC and MAPKs) and insulin-dependent (PI 3-kinase/Akt and mTOR) pathways. It also suggested that there is a crosstalk between the two signaling pathways of glucose metabolism in skeletal muscle cells. These results could be confirmed from the findings of GLUT4 translocation. Taken together, AMPK plays a major role in the effects of saffron on glucose uptake and insulin sensitivity in skeletal muscle cells. Our study provides important insights for the possible mechanism of action of saffron and its potential as a therapeutic agent in diabetic patients.

  11. Diuretics Prevent Thiazolidinedione-Induced Cardiac Hypertrophy without Compromising Insulin-Sensitizing Effects in Mice

    Science.gov (United States)

    Chang, Cherng-Shyang; Tsai, Pei-Jane; Sung, Junne-Ming; Chen, Ju-Yi; Ho, Li-Chun; Pandya, Kumar; Maeda, Nobuyo; Tsai, Yau-Sheng

    2015-01-01

    Much concern has arisen regarding critical adverse effects of thiazolidinediones (TZDs), including rosiglitazone and pioglitazone, on cardiac tissue. Although TZD-induced cardiac hypertrophy (CH) has been attributed to an increase in plasma volume or a change in cardiac nutrient preference, causative roles have not been established. To test the hypothesis that volume expansion directly mediates rosiglitazone-induced CH, mice were fed a high-fat diet with rosiglitazone, and cardiac and metabolic consequences were examined. Rosiglitazone treatment induced volume expansion and CH in wild-type and PPARγ heterozygous knockout (Pparg+/−) mice, but not in mice defective for ligand binding (PpargP465L/+). Cotreatment with the diuretic furosemide in wild-type mice attenuated rosiglitazone-induced CH, hypertrophic gene reprogramming, cardiomyocyte apoptosis, hypertrophy-related signal activation, and left ventricular dysfunction. Similar changes were observed in mice treated with pioglitazone. The diuretics spironolactone and trichlormethiazide, but not amiloride, attenuated rosiglitazone effects on volume expansion and CH. Interestingly, expression of glucose and lipid metabolism genes in the heart was altered by rosiglitazone, but these changes were not attenuated by furosemide cotreatment. Importantly, rosiglitazone-mediated whole-body metabolic improvements were not affected by furosemide cotreatment. We conclude that releasing plasma volume reduces adverse effects of TZD-induced volume expansion and cardiac events without compromising TZD actions in metabolic switch in the heart and whole-body insulin sensitivity. PMID:24287404

  12. Gender differences in skeletal muscle substrate metabolism - molecular mechanisms and insulin sensitivity

    DEFF Research Database (Denmark)

    Lundsgaard, Anne-Marie; Kiens, Bente

    2014-01-01

    favorable effect on glucose homeostasis, and the available evidence from hyperinsulinemic-euglycemic clamp studies is summarized to delineate whether there is a gender difference in whole-body insulin sensitivity and in particular insulin-stimulated glucose uptake of skeletal muscle. Whether an eventual...... fasted state, and during periods of physical activity and recovery. Together, handling of carbohydrate and lipids and regulation of their utilization in skeletal muscle have implications for whole-body glucose homeostasis in men and women. 17-β estradiol is the most important female sex hormone, and the...

  13. Gender dimorphism in aspartame-induced impairment of spatial cognition and insulin sensitivity.

    Directory of Open Access Journals (Sweden)

    Kate S Collison

    Full Text Available Previous studies have linked aspartame consumption to impaired retention of learned behavior in rodents. Prenatal exposure to aspartame has also been shown to impair odor-associative learning in guinea pigs; and recently, aspartame-fed hyperlipidemic zebrafish exhibited weight gain, hyperglycemia and acute swimming defects. We therefore investigated the effects of chronic lifetime exposure to aspartame, commencing in utero, on changes in blood glucose parameters, spatial learning and memory in C57BL/6J mice. Morris Water Maze (MWM testing was used to assess learning and memory, and a random-fed insulin tolerance test was performed to assess glucose homeostasis. Pearson correlation analysis was used to investigate the associations between body characteristics and MWM performance outcome variables. At 17 weeks of age, male aspartame-fed mice exhibited weight gain, elevated fasting glucose levels and decreased insulin sensitivity compared to controls (P<0.05. Females were less affected, but had significantly raised fasting glucose levels. During spatial learning trials in the MWM (acquisition training, the escape latencies of male aspartame-fed mice were consistently higher than controls, indicative of learning impairment. Thigmotactic behavior and time spent floating directionless was increased in aspartame mice, who also spent less time searching in the target quadrant of the maze (P<0.05. Spatial learning of female aspartame-fed mice was not significantly different from controls. Reference memory during a probe test was affected in both genders, with the aspartame-fed mice spending significantly less time searching for the former location of the platform. Interestingly, the extent of visceral fat deposition correlated positively with non-spatial search strategies such as floating and thigmotaxis, and negatively with time spent in the target quadrant and swimming across the location of the escape platform. These data suggest that lifetime

  14. Gender dimorphism in aspartame-induced impairment of spatial cognition and insulin sensitivity.

    Science.gov (United States)

    Collison, Kate S; Makhoul, Nadine J; Zaidi, Marya Z; Saleh, Soad M; Andres, Bernard; Inglis, Angela; Al-Rabiah, Rana; Al-Mohanna, Futwan A

    2012-01-01

    Previous studies have linked aspartame consumption to impaired retention of learned behavior in rodents. Prenatal exposure to aspartame has also been shown to impair odor-associative learning in guinea pigs; and recently, aspartame-fed hyperlipidemic zebrafish exhibited weight gain, hyperglycemia and acute swimming defects. We therefore investigated the effects of chronic lifetime exposure to aspartame, commencing in utero, on changes in blood glucose parameters, spatial learning and memory in C57BL/6J mice. Morris Water Maze (MWM) testing was used to assess learning and memory, and a random-fed insulin tolerance test was performed to assess glucose homeostasis. Pearson correlation analysis was used to investigate the associations between body characteristics and MWM performance outcome variables. At 17 weeks of age, male aspartame-fed mice exhibited weight gain, elevated fasting glucose levels and decreased insulin sensitivity compared to controls (Paspartame-fed mice were consistently higher than controls, indicative of learning impairment. Thigmotactic behavior and time spent floating directionless was increased in aspartame mice, who also spent less time searching in the target quadrant of the maze (Paspartame-fed mice was not significantly different from controls. Reference memory during a probe test was affected in both genders, with the aspartame-fed mice spending significantly less time searching for the former location of the platform. Interestingly, the extent of visceral fat deposition correlated positively with non-spatial search strategies such as floating and thigmotaxis, and negatively with time spent in the target quadrant and swimming across the location of the escape platform. These data suggest that lifetime exposure to aspartame, commencing in utero, may affect spatial cognition and glucose homeostasis in C57BL/6J mice, particularly in males.

  15. Gender dimorphism in aspartame-induced impairment of spatial cognition and insulin sensitivity.

    Science.gov (United States)

    Collison, Kate S; Makhoul, Nadine J; Zaidi, Marya Z; Saleh, Soad M; Andres, Bernard; Inglis, Angela; Al-Rabiah, Rana; Al-Mohanna, Futwan A

    2012-01-01

    Previous studies have linked aspartame consumption to impaired retention of learned behavior in rodents. Prenatal exposure to aspartame has also been shown to impair odor-associative learning in guinea pigs; and recently, aspartame-fed hyperlipidemic zebrafish exhibited weight gain, hyperglycemia and acute swimming defects. We therefore investigated the effects of chronic lifetime exposure to aspartame, commencing in utero, on changes in blood glucose parameters, spatial learning and memory in C57BL/6J mice. Morris Water Maze (MWM) testing was used to assess learning and memory, and a random-fed insulin tolerance test was performed to assess glucose homeostasis. Pearson correlation analysis was used to investigate the associations between body characteristics and MWM performance outcome variables. At 17 weeks of age, male aspartame-fed mice exhibited weight gain, elevated fasting glucose levels and decreased insulin sensitivity compared to controls (Pglucose levels. During spatial learning trials in the MWM (acquisition training), the escape latencies of male aspartame-fed mice were consistently higher than controls, indicative of learning impairment. Thigmotactic behavior and time spent floating directionless was increased in aspartame mice, who also spent less time searching in the target quadrant of the maze (Paspartame-fed mice was not significantly different from controls. Reference memory during a probe test was affected in both genders, with the aspartame-fed mice spending significantly less time searching for the former location of the platform. Interestingly, the extent of visceral fat deposition correlated positively with non-spatial search strategies such as floating and thigmotaxis, and negatively with time spent in the target quadrant and swimming across the location of the escape platform. These data suggest that lifetime exposure to aspartame, commencing in utero, may affect spatial cognition and glucose homeostasis in C57BL/6J mice, particularly in

  16. Consumption of a diet low in advanced glycation end products for 4 weeks improves insulin sensitivity in overweight women

    DEFF Research Database (Denmark)

    Mark, Alicja Budek; Poulsen, Malene Wibe; Andersen, Stine;

    2014-01-01

    OBJECTIVE High-heat cooking of food induces the formation of advanced glycation end products (AGEs), which are thought to impair glucose metabolism in type 2 diabetic patients. High intake of fructose might additionally affect endogenous formation of AGEs. This parallel intervention study...... investigated whether the addition of fructose or cooking methods influencing the AGE content of food affect insulin sensitivity in overweight individuals. RESEARCH DESIGN AND METHODS Seventy-four overweight women were randomized to follow either a high- or low-AGE diet for 4 weeks, together with consumption...... AGE concentrations were measured (liquid chromatography tandem mass spectrometry) to estimate AGE intake and excretion. RESULTS When adjusted for changes in anthropometric measures during the intervention, the low-AGE diet decreased urinary AGEs, fasting insulin concentrations, and HOMA-IR, compared...

  17. Resolution of lipohypertrophy following change of short-acting insulin to insulin lispro (Humalog).

    Science.gov (United States)

    Roper, N A; Bilous, R W

    1998-12-01

    Lipohypertrophy as a local complication of insulin therapy is well recognized. Despite improvements in insulin purity and the introduction of recombinant human insulin its prevalence has remained high. Rotation of injection sites can reduce the frequency of the problem but does not abolish it. The importance of this complication is not only cosmetic but also in its impact on insulin absorption, and hence glycaemic control. We report a patient who had intractable lipohypertrophy with human recombinant insulin but experienced no such problem when converted onto the insulin analogue lispro. We suggest that the faster speed of absorption of insulin lispro may lead to less hypertrophic stimulation of subcutaneous adipocytes. This difference may be clinically useful in susceptible individuals.

  18. Insulin analogues: have they changed insulin treatment and improved glycaemic control?

    DEFF Research Database (Denmark)

    Madsbad, Sten

    2002-01-01

    To improve insulin therapy, new insulin analogues have been developed. Two fast-acting analogues with a more rapid onset of effect and a shorter duration of action combined with a low day-to-day variation in absorption rate are now available. Despite this favourable time-action profile most studies....... This is probably the main explanation for the absence of improvement in overall glycaemic control when compared with regular human insulin. A tendency to a reduction in hypoglycaemic events during treatment with fast-acting analogues has been observed in most studies. Recent studies have indicated that NPH insulin...... administered several times daily at mealtimes can improve glycaemic control without increasing the risk of hypoglycaemia. The fast-acting analogues are now also available as insulin mixed with NPH. Insulin glargine is a new long-acting insulin which is soluble and precipitates after injection, resulting...

  19. Increase of insulin sensitivity in diabetic rats received Die-Huang-Wan, a herbal mixture used in Chinese traditional medicine

    Institute of Scientific and Technical Information of China (English)

    WU Yang-Chang; HSU Jen-Hao; LIU I-Min; LIOU Shorong-Shii; SU Hui-Chen; CHENG Juei-Tang

    2002-01-01

    AIM: Effects on insulin sensitivity of Die-Huang-Wan, the herbal mixture widely used to treat diabetic disorder in Chinese traditional medicine, were investigated in vivo. METHODS: The obese Zucker rats were employed as insulin-resistant animal model. Also, insulin-resistance was induced by the repeated intraperitoneal injections of long-acting human insulin at 0.5 U/kg three times daily into adult male Wistar rats. Insulin resistance was identified using the loss of tolbutamide (10 mg/kg) or electroacupuncture (EA)-induced plasma glucose lowering action. The plasma glucose concentration was examined by glucose oxidase assay. RESULTS: The plasma glucose-lowering action induced by tolbutamide was significantly enhanced in obese Zucker rats receiving the repeated administration of Die-Huang-Wan at dosage of 26 mg/kg for 3 d. Furthermore, administration of Die-Huang-Wan delayed the formation of insulin resistance in rats that were induced by the daily repeated injection of human long-acting insulin at 0.5 U/kg three times daily and identified by the loss of tolbutamide- or EA-induced hypoglycemia. In streptozotocininduced diabetic rats, oral administration of metformin at 320 mg/kg once daily made an increase of the response to exogenous short-acting human insulin 15 d later. This is consistent with the view that metformin can increase insulin sensitivity. Similar treatment with Die-Huang-Wan at an effective dose (26.0 mg/kg) also increased the plasma glucose lowering action of exogenous insulin at 10 d later. The effect of Die-Huang-Wan on insulin sensitivity seems to produce more rapidly than that of metformin. CONCLUSION: The present study found that oral administration of Die-Huang-Wan increased insulin sensitivity and delayed the development of insulin resistance in rats.

  20. An acute bout of endurance exercise but not sprint interval exercise enhances insulin sensitivity.

    Science.gov (United States)

    Brestoff, Jonathan R; Clippinger, Benjamin; Spinella, Thomas; von Duvillard, Serge P; Nindl, Bradley C; Nindl, Bradley; Arciero, Paul J

    2009-02-01

    An acute bout of endurance exercise (EE) enhances insulin sensitivity, but the effects of sprint interval exercise (SIE) have not yet been described. We sought to compare insulin sensitivity at baseline and after an acute bout of EE and SIE in healthy men (n = 8) and women (n = 5) (age, 20.7 +/- 0.3 years; peak oxygen consumption (VO2 peak), 42.6 +/- 1.7 mL.kg(-1).min(-1); men vs. women, p > 0.05). Pearson's correlation coefficients between ISI-COMP and ISI-HOMA for each condition were highly correlated (p < 0.01), and followed similar patterns of response. ISI-COMP(EE) was 71.4% higher than ISI-COMP(B) (8.4 +/- 1.4 vs. 4.9 +/- 1.0; p < 0.01) and 40.0% higher than ISI-COMPSIE (8.4 +/- 1.4 vs. 6.0 +/- 1.5; p < 0.05), but there was no difference between ISI-COMP(B) and ISI-COMP(SIE) (p = 0.182). VO(2 peak) was highly correlated with both ISI-COMP and ISI-HOMA during baseline and SIE test conditions (p < 0.02). These findings demonstrate that an acute bout of EE, but not SIE, increases insulin sensitivity relative to a no-exercise control condition in healthy males and females. While these findings underscore the use of regular EE as an effective intervention strategy against insulin resistance, additional research examining repeated sessions of SIE on insulin sensitivity is warranted.

  1. Sensitive detection of human insulin using a designed combined pore approach.

    Science.gov (United States)

    Lei, Chang; Noonan, Owen; Jambhrunkar, Siddharth; Qian, Kun; Xu, Chun; Zhang, Jun; Nouwens, Amanda; Yu, Chengzhong

    2014-06-25

    A unique combined pore approach to the sensitive detection of human insulin is developed. Through a systematic study to understand the impact of pore size and surface chemistry of nanoporous materials on their enrichment and purification performance, the advantages of selected porous materials are integrated to enhance detection sensitivity in a unified two-step process. In the first purification step, a rationally designed large pore material (ca. 100 nm in diameter) is chosen to repel the interferences from nontarget molecules. In the second enrichment step, a hydrophobically modified mesoporous material with a pore size of 5 nm is selected to enrich insulin molecules. A low detection limit of 0.05 ng mL(-1) in artificial urine is achieved by this advanced approach, similar to most antibody-based analysis protocols. This designer approach is efficient and low cost, and thus has great potential in the sensitive detection of biomolecules in complex biological systems. PMID:24599559

  2. Synthesis and evaluation of temperature- and glucose-sensitive nanoparticles based on phenylboronic acid and N-vinylcaprolactam for insulin delivery.

    Science.gov (United States)

    Wu, Jun-Zi; Bremner, David H; Li, He-Yu; Sun, Xiao-Zhu; Zhu, Li-Min

    2016-12-01

    Poly N-vinylcaprolactam-co-acrylamidophenylboronic acid p(NVCL-co-AAPBA) was prepared from N-vinylcaprolactam (NVCL) and 3-acrylamidophenylboronic acid (AAPBA), using 2,2-azobisisobutyronitrile (AIBN) as initiator. The synthesis and structure of the polymer were examined by Fourier Transform infrared spectroscopy (FT-IR) and (1)H-NMR. Dynamic light scattering (DLS), lower critical solution temperature (LCST) and transmission electron microscopy (TEM) were utilized to characterize the nanoparticles, CD spectroscopy was used to determine if there were any changes to the conformation of the insulin, and cell and animal toxicity were also investigated. The prepared nanoparticles were found to be monodisperse submicron particles and were glucose- and temperature-sensitive. In addition, the nanoparticles have good insulin-loading characteristics, do not affect the conformation of the insulin and show low-toxicity to cells and animals. These p(NVCL-co-AAPBA) nanoparticles may have some value for insulin or other hypoglycemic protein delivery. PMID:27612799

  3. Bezafibrate Improves Insulin Sensitivity and Metabolic Flexibility in STZ-Induced Diabetic Mice.

    Science.gov (United States)

    Franko, Andras; Huypens, Peter; Neschen, Susanne; Irmler, Martin; Rozman, Jan; Rathkolb, Birgit; Neff, Frauke; Prehn, Cornelia; Dubois, Guillaume; Baumann, Martina; Massinger, Rebecca; Gradinger, Daniel; Przemeck, Gerhard K H; Repp, Birgit; Aichler, Michaela; Feuchtinger, Annette; Schommers, Philipp; Stöhr, Oliver; Sanchez-Lasheras, Carmen; Adamski, Jerzy; Peter, Andreas; Prokisch, Holger; Beckers, Johannes; Walch, Axel K; Fuchs, Helmut; Wolf, Eckhard; Schubert, Markus; Wiesner, Rudolf J; Hrabě de Angelis, Martin

    2016-09-01

    Bezafibrate (BEZ), a pan activator of peroxisome proliferator-activated receptors (PPARs), has been generally used to treat hyperlipidemia for decades. Clinical trials with type 2 diabetes patients indicated that BEZ also has beneficial effects on glucose metabolism, although the underlying mechanisms of these effects remain elusive. Even less is known about a potential role for BEZ in treating type 1 diabetes. Here we show that BEZ markedly improves hyperglycemia and glucose and insulin tolerance in mice with streptozotocin (STZ)-induced diabetes, an insulin-deficient mouse model of type 1 diabetes. BEZ treatment of STZ mice significantly suppressed the hepatic expression of genes that are annotated in inflammatory processes, whereas the expression of PPAR and insulin target gene transcripts was increased. Furthermore, BEZ-treated mice also exhibited improved metabolic flexibility as well as an enhanced mitochondrial mass and function in the liver. Finally, we show that the number of pancreatic islets and the area of insulin-positive cells tended to be higher in BEZ-treated mice. Our data suggest that BEZ may improve impaired glucose metabolism by augmenting hepatic mitochondrial performance, suppressing hepatic inflammatory pathways, and improving insulin sensitivity and metabolic flexibility. Thus, BEZ treatment might also be useful for patients with impaired glucose tolerance or diabetes. PMID:27284107

  4. Hypothalamic neurogenesis is not required for the improved insulin sensitivity following exercise training.

    Science.gov (United States)

    Borg, Melissa L; Lemus, Moyra; Reichenbach, Alex; Selathurai, Ahrathy; Oldfield, Brian J; Andrews, Zane B; Watt, Matthew J

    2014-11-01

    Neurons within the hypothalamic arcuate nucleus (ARC) are important regulators of energy balance. Recent studies suggest that neurogenesis in the ARC is an important regulator of body mass in response to pharmacological stressors. Regular exercise training improves insulin action, and is a primary treatment modality for obesity and type 2 diabetes. We examined whether exercise training causes hypothalamic neurogenesis and whether this contributes to exercise-induced improvements in insulin action. Short-term exercise in adult mice induced a proneurogenic transcriptional program involving growth factors, cell proliferation, and neurogenic regulators in the hypothalamus. Daily exercise training for 7 days increased hypothalamic cell proliferation 3.5-fold above that of sedentary mice, and exercise-induced cell proliferation was maintained in diet-induced obese mice. Colocalization studies indicated negligible neurogenesis in the ARC of sedentary or exercise-trained mice. Blocking cell proliferation via administration of the mitotic blocker arabinosylcytosine (AraC) did not affect food intake or body mass in obese mice. While 4 weeks of exercise training improved whole-body insulin sensitivity compared with sedentary mice, insulin action was not affected by AraC administration. These data suggest that regular exercise training induces significant non-neuronal cell proliferation in the hypothalamus of obese mice, but this proliferation is not required for enhanced insulin action.

  5. Insulin sensitivity is normalized in the third generation (F3 offspring of developmentally programmed insulin resistant (F2 rats fed an energy-restricted diet

    Directory of Open Access Journals (Sweden)

    Martin John F

    2008-10-01

    Full Text Available Abstract Background/Aims The offspring and grandoffspring of female rats fed low protein diets during pregnancy and lactation, but fed nutritionally adequate diets thereafter, have been shown to exhibit altered insulin sensitivity in adulthood. The current study investigates the insulin sensitivity of the offspring and grandoffspring of female rats fed low protein diets during pregnancy, and then maintained on energy-restricted diets post weaning over three generations. Methods Female Sprague Dawley rats (F0 were mated with control males and protein malnourished during pregnancy/lactation. F1 offspring were then weaned to adequate but energy-restricted diets into adulthood. F1 dams were fed energy-restricted diets throughout pregnancy/lactation. F2 offspring were also fed energy-restricted diets post weaning. F2 pregnant dams were maintained as described above. Their F3 offspring were split into two groups; one was maintained on the energy-restricted diet, the other was maintained on an adequate diet consumed ad libitum post weaning. Results F2 animals fed energy-restricted diets were insulin resistant (p ad libitum postweaning diets (p Conclusion Maternal energy-restriction did not consistently program reduced insulin sensitivity in offspring over three consecutive generations. The reasons for this remain unclear. It is possible that the intergenerational transmission of developmentally programmed insulin resistance is determined in part by the relative insulin sensitivity of the mother during pregnancy/lactation.

  6. Spironolactone in the treatment of polycystic ovary syndrome: effects on clinical features, insulin sensitivity and lipid profile.

    Science.gov (United States)

    Zulian, E; Sartorato, P; Benedini, S; Baro, G; Armanini, D; Mantero, F; Scaroni, C

    2005-01-01

    This prospective clinical trial was designed to assess the effects of a long-term therapy with spironolactone, with and without dietary-induced weight-loss, on clinical features, lipid profile and insulin levels in women with polycystic ovary syndrome (PCOS). Twenty-five patients (range of age 16-32 yr; 13 lean and 12 overweight) fulfilling formal diagnostic criteria for PCOS (oligomenorrhea and/or amenorrhea, biochemical and/or clinical evidence of hyperadrogenism) were studied at baseline and then received oral spironolactone (100 mg/die) for 12 months; association with lifestyle modifications was recommended to all over-weight patients. Clinical, endocrine and metabolic parameters [oral glucose tolerance test (OGTT), lipid profile] were measured at baseline and at the end of the antiandrogen treatment. The therapy was associated with a significant average decline of triglycerides in overweight subjects and with increased HDL-cholesterol levels in lean patients. The insulin levels at 60 min during OGTT, homeostasis model assessment-insulin resistance and area under curve of insulin were significantly lowered in overweight women after 12 months of spironolactone and weight loss and no negative changes in insulin secretion and sensitivity were observed in PCOS women after pharmacological treatment alone. The efficacy of spironolactone on the androgenic clinical aspects of PCOS has been confirmed in this study. Furthermore, our data show that long-term treatment with spironolactone exerts no negative effects on lipoprotein profile and glucose metabolism; more relevant beneficial effects on glucose and lipid metabolism were observed when the antiandrogen was associated with weight loss in overweight PCOS women. PMID:15816371

  7. Changes in transferrin are related to changes in insulin resistance: the SLIM study

    NARCIS (Netherlands)

    Roumen, C.; Feskens, E.J.M.; Jansen, E.H.; Saris, W.H.; Blaak, E.E.

    2008-01-01

    Aims To determine the effect of a lifestyle intervention on serum transferrin and ferritin levels and the relationship between changes in transferrin and ferritin and changes in glucose tolerance and insulin resistance. Methods Randomized controlled lifestyle intervention directed at a healthy diet

  8. Alterations of Mitochondrial Function and Insulin Sensitivity in Human Obesity and Diabetes Mellitus.

    Science.gov (United States)

    Koliaki, Chrysi; Roden, Michael

    2016-07-17

    Mitochondrial function refers to a broad spectrum of features such as resting mitochondrial activity, (sub)maximal oxidative phosphorylation capacity (OXPHOS), and mitochondrial dynamics, turnover, and plasticity. The interaction between mitochondria and insulin sensitivity is bidirectional and varies depending on tissue, experimental model, methodological approach, and features of mitochondrial function tested. In human skeletal muscle, mitochondrial abnormalities may be inherited (e.g., lower mitochondrial content) or acquired (e.g., impaired OXPHOS capacity and plasticity). Abnormalities ultimately lead to lower mitochondrial functionality due to or resulting in insulin resistance and type 2 diabetes mellitus. Similar mechanisms can also operate in adipose tissue and heart muscle. In contrast, mitochondrial oxidative capacity is transiently upregulated in the liver of obese insulin-resistant humans with or without fatty liver, giving rise to oxidative stress and declines in advanced fatty liver disease. These data suggest a highly tissue-specific interaction between insulin sensitivity and oxidative metabolism during the course of metabolic diseases in humans. PMID:27146012

  9. Stevioside from Stevia rebaudiana Bertoni Increases Insulin Sensitivity in 3T3-L1 Adipocytes

    Directory of Open Access Journals (Sweden)

    Nabilatul Hani Mohd-Radzman

    2013-01-01

    Full Text Available Stevioside from Stevia rebaudiana has been reported to exert antihyperglycemic effects in both rat and human subjects. There have been few studies on these effects in vitro. In this paper, radioactive glucose uptake assay was implemented in order to assess improvements in insulin sensitivity in 3T3-L1 cells by elevation of glucose uptake following treatment with stevioside. Oil Red-O staining and MTT assay were utilized to confirm adipocyte differentiation and cell viability, respectively. Findings from this research showed a significant increase in absorbance values in mature adipocytes following Oil Red-O staining, confirming the differentiation process. Stevioside was noncytotoxic to 3T3-L1 cells as cell viability was reduced by a maximum of 17%, making it impossible to determine its IC50. Stevioside increased glucose uptake activities by 2.1 times (p<0.001 in normal conditions and up to 4.4 times (p<0.001 in insulin-resistant states. At times, this increase was higher than that seen in positive control group treated with rosiglitazone maleate, an antidiabetic agent. Expressions of pY20 and p-IRS1 which were measured via Western blot were improved by stevioside treatment. In conclusion, stevioside has direct effects on 3T3-L1 insulin sensitivity via increase in glucose uptake and enhanced expression of proteins involved in insulin-signalling pathway.

  10. Methazolamide Is a New Hepatic Insulin Sensitizer That Lowers Blood Glucose In Vivo

    Science.gov (United States)

    Konstantopoulos, Nicky; Molero, Juan C.; McGee, Sean L.; Spolding, Briana; Connor, Tim; de Vries, Melissa; Wanyonyi, Stephen; Fahey, Richard; Morrison, Shona; Swinton, Courtney; Jones, Sharon; Cooper, Adrian; Garcia-Guerra, Lucia; Foletta, Victoria C.; Krippner, Guy; Andrikopoulos, Sofianos; Walder, Ken R.

    2012-01-01

    We previously used Gene Expression Signature technology to identify methazolamide (MTZ) and related compounds with insulin sensitizing activity in vitro. The effects of these compounds were investigated in diabetic db/db mice, insulin-resistant diet-induced obese (DIO) mice, and rats with streptozotocin (STZ)-induced diabetes. MTZ reduced fasting blood glucose and HbA1c levels in db/db mice, improved glucose tolerance in DIO mice, and enhanced the glucose-lowering effects of exogenous insulin administration in rats with STZ-induced diabetes. Hyperinsulinemic-euglycemic clamps in DIO mice revealed that MTZ increased glucose infusion rate and suppressed endogenous glucose production. Whole-body or cellular oxygen consumption rate was not altered, suggesting MTZ may inhibit glucose production by different mechanism(s) to metformin. In support of this, MTZ enhanced the glucose-lowering effects of metformin in db/db mice. MTZ is known to be a carbonic anhydrase inhibitor (CAI); however, CAIs acetazolamide, ethoxyzolamide, dichlorphenamide, chlorthalidone, and furosemide were not effective in vivo. Our results demonstrate that MTZ acts as an insulin sensitizer that suppresses hepatic glucose production in vivo. The antidiabetic effect of MTZ does not appear to be a function of its known activity as a CAI. The additive glucose-lowering effect of MTZ together with metformin highlights the potential utility for the management of type 2 diabetes. PMID:22586591

  11. The Effect of Regular Exercise on Insulin Sensitivity in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Way, Kimberley L; Hackett, Daniel A; Baker, Michael K; Johnson, Nathan A

    2016-08-01

    The purpose of this study was to examine the effect of regular exercise training on insulin sensitivity in adults with type 2 diabetes mellitus (T2DM) using the pooled data available from randomised controlled trials. In addition, we sought to determine whether short-term periods of physical inactivity diminish the exercise-induced improvement in insulin sensitivity. Eligible trials included exercise interventions that involved ≥3 exercise sessions, and reported a dynamic measurement of insulin sensitivity. There was a significant pooled effect size (ES) for the effect of exercise on insulin sensitivity (ES, -0.588; 95% confidence interval [CI], -0.816 to -0.359; P<0.001). Of the 14 studies included for meta-analyses, nine studies reported the time of data collection from the last exercise bout. There was a significant improvement in insulin sensitivity in favour of exercise versus control between 48 and 72 hours after exercise (ES, -0.702; 95% CI, -1.392 to -0.012; P=0.046); and this persisted when insulin sensitivity was measured more than 72 hours after the last exercise session (ES, -0.890; 95% CI, -1.675 to -0.105; P=0.026). Regular exercise has a significant benefit on insulin sensitivity in adults with T2DM and this may persist beyond 72 hours after the last exercise session. PMID:27535644

  12. No effect of bicarbonate treatment on insulin sensitivity and glucose control in non-diabetic older adults

    OpenAIRE

    Harris, Susan S.; Dawson-Hughes, Bess

    2010-01-01

    Chronic mild metabolic acidosis is common among older adults, and limited evidence suggests that it may contribute to insulin resistance and type-2 diabetes. This analysis was conducted to determine whether bicarbonate supplementation, an alkalinizing treatment, improves insulin sensitivity or glucose control in non-diabetic older adults. Fasting blood glucose and insulin were measured in stored samples from subjects who had completed a 3-month clinical trial of bicarbonate supplementation to...

  13. Insulin analogues: have they changed insulin treatment and improved glycaemic control?

    DEFF Research Database (Denmark)

    Madsbad, Sten

    2002-01-01

    To improve insulin therapy, new insulin analogues have been developed. Two fast-acting analogues with a more rapid onset of effect and a shorter duration of action combined with a low day-to-day variation in absorption rate are now available. Despite this favourable time-action profile most studi......, the new fast-acting analogues have not achieved the expected commercial success, which emphasises the need for new strategies for basal insulin supplementation, exercise, diet and blood glucose monitoring....

  14. Activation of G proteins by GIV-GEF is a pivot point for insulin resistance and sensitivity.

    Science.gov (United States)

    Ma, Gary S; Lopez-Sanchez, Inmaculada; Aznar, Nicolas; Kalogriopoulos, Nicholas; Pedram, Shabnam; Midde, Krishna; Ciaraldi, Theodore P; Henry, Robert R; Ghosh, Pradipta

    2015-11-15

    Insulin resistance (IR) is a metabolic disorder characterized by impaired insulin signaling and cellular glucose uptake. The current paradigm for insulin signaling centers upon the insulin receptor (InsR) and its substrate IRS1; the latter is believed to be the sole conduit for postreceptor signaling. Here we challenge that paradigm and show that GIV/Girdin, a guanidine exchange factor (GEF) for the trimeric G protein Gαi, is another major hierarchical conduit for the metabolic insulin response. By virtue of its ability to directly bind InsR, IRS1, and phosphoinositide 3-kinase, GIV serves as a key hub in the immediate postreceptor level, which coordinately enhances the metabolic insulin response and glucose uptake in myotubes via its GEF function. Site-directed mutagenesis or phosphoinhibition of GIV-GEF by the fatty acid/protein kinase C-theta pathway triggers IR. Insulin sensitizers reverse phosphoinhibition of GIV and reinstate insulin sensitivity. We also provide evidence for such reversible regulation of GIV-GEF in skeletal muscles from patients with IR. Thus GIV is an essential upstream component that couples InsR to G-protein signaling to enhance the metabolic insulin response, and impairment of such coupling triggers IR. We also provide evidence that GIV-GEF serves as therapeutic target for exogenous manipulation of physiological insulin response and reversal of IR in skeletal muscles. PMID:26378251

  15. Association of obesity risk SNPs in PCSK1 with insulin sensitivity and proinsulin conversion

    Directory of Open Access Journals (Sweden)

    Häring Hans-Ulrich

    2010-06-01

    Full Text Available Abstract Background Prohormone convertase 1 is involved in maturation of peptides. Rare mutations in gene PCSK1, encoding this enzyme, cause childhood obesity and abnormal glucose homeostasis with elevated proinsulin concentrations. Common single nucleotide polymorphisms (SNPs within this gene, rs6232 and rs6235, are associated with obesity. We studied whether these SNPs influence the prediabetic traits insulin resistance, β-cell dysfunction, or glucose intolerance. Methods We genotyped 1498 German subjects for SNPs rs6232 and rs6235 within PCSK1. The subjects were metabolically characterized by oral glucose tolerance test with glucose, insulin, proinsulin, and C-peptide measurements. A subgroup of 512 subjects underwent a hyperinsulinemic-euglycemic clamp. Results The minor allele frequencies were 25.8% for SNP rs6235 and 6.0% for rs6232. After adjustment for sex and age, we found no association of SNPs rs6235 and rs6232 with BMI or other weight-related traits (all p ≥ 0.07. Both minor alleles, adjusted for sex, age, BMI and insulin sensitivity were associated with elevated AUCproinsulin and AUCproinsulin/AUCinsulin (rs6235: padditive model ≤ 0.009, effect sizes 8/8%, rs6232: pdominant model ≤ 0.01, effect sizes 10/21%. Insulin secretion was not affected by the variants (different secretion parameters, all p ≥ 0.08. The minor allele of SNP rs6232 was additionally associated with 15% higher OGTT-derived and 19% higher clamp-derived insulin sensitivity (pdom ≤ 0.0047, 4.5% lower HOMAIR (pdom = 0.02 and 3.5% lower 120-min glucose (pdom = 0.0003 independently of BMI and proinsulin conversion. SNP rs6235 was not associated with parameters of glucose metabolism. Conclusions Like rare mutations in PCSK1, the more common variants tested determine glucose-stimulated proinsulin conversion, but not insulin secretion. In addition, rs6232, encoding the amino acid exchange N221D, influences insulin sensitivity and glucose homeostasis.

  16. pH sensitive thiolated cationic hydrogel for oral insulin delivery.

    Science.gov (United States)

    Sonia, T A; Sharma, Chandra P

    2014-04-01

    The objective of this work is to study the efficacy of pH sensitive thiolated Polydimethylaminoethylmethacrylate for oral delivery of insulin. Synthesis of pH sensitive thiolated Polydimethylaminoethylmethacrylate (PDCPA) was carried out by crosslinking Polymethacrylic acid with thiolated Polydimethylaminoethylmethacrylate (PDCys) via carbodiimide chemistry. Prior to in vivo experiment, various physicochemical and biological characterisation were carried out to evaluate the efficacy of PDCPA. Modification was confirmed by IR and NMR spectroscopy. The particle size was found to be 284 nm with a zeta potential of 37.3+/-1.58 mV. Texture analyser measurements showed that PDCPA is more mucoadhesive than the parent polymer. Transepithelial electrical measurements showed a reduction of greater than 50% on incubation with PDCPA particles. Permeation studies showed that PDCPA is more permeable than the parent polymer. On in vivo evaluation on male diabetic rats, insulin loaded PDCPA exhibited a blood glucose reduction of 19%. PMID:24734516

  17. Receptor for Advanced Glycation End Products Regulates Adipocyte Hypertrophy and Insulin Sensitivity in Mice

    OpenAIRE

    Monden, Masayo; Koyama, Hidenori; Otsuka, Yoshiko; Morioka, Tomoaki; Mori, Katsuhito; Shoji, Takuhito; Mima, Yohei; Motoyama, Koka; Fukumoto, Shinya; Shioi, Atsushi; Emoto, Masanori; Yamamoto, Yasuhiko; Yamamoto, Hiroshi; Nishizawa, Yoshiki; Kurajoh, Masafumi

    2013-01-01

    Receptor for advanced glycation end products (RAGE) has been shown to be involved in adiposity as well as atherosclerosis even in nondiabetic conditions. In this study, we examined mechanisms underlying how RAGE regulates adiposity and insulin sensitivity. RAGE overexpression in 3T3-L1 preadipocytes using adenoviral gene transfer accelerated adipocyte hypertrophy, whereas inhibitions of RAGE by small interfering RNA significantly decrease adipocyte hypertrophy. Furthermore, double knockdown o...

  18. Stevioside from Stevia rebaudiana Bertoni Increases Insulin Sensitivity in 3T3-L1 Adipocytes

    OpenAIRE

    Nabilatul Hani Mohd-Radzman; Wan Iryani Wan Ismail; Siti Safura Jaapar; Zainah Adam; Aishah Adam

    2013-01-01

    Stevioside from Stevia rebaudiana has been reported to exert antihyperglycemic effects in both rat and human subjects. There have been few studies on these effects in vitro. In this paper, radioactive glucose uptake assay was implemented in order to assess improvements in insulin sensitivity in 3T3-L1 cells by elevation of glucose uptake following treatment with stevioside. Oil Red-O staining and MTT assay were utilized to confirm adipocyte differentiation and cell viability, respectively. Fi...

  19. Brown Adipose Tissue Improves Whole-Body Glucose Homeostasis and Insulin Sensitivity in Humans

    OpenAIRE

    Chondronikola, Maria; Volpi, Elena; Børsheim, Elisabet; Porter, Craig; Annamalai, Palam; Enerbäck, Sven; Lidell, Martin E.; Saraf, Manish K.; Sebastien M Labbe; Hurren, Nicholas M; Yfanti, Christina; Chao, Tony; Andersen, Clark R.; Cesani, Fernando; Hawkins, Hal

    2014-01-01

    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. To investigate whether BAT activation alters whole-body glucose homeostasis and insulin sensitivity in humans, we studied seven BAT-positive (BAT+) men and five BAT-negative (BAT−) men under thermon...

  20. Conjugated Linoleic Acid in Humans: Regulation of Adiposity and Insulin Sensitivity1,2

    OpenAIRE

    Brown, J. Mark; McIntosh, Michael K.

    2003-01-01

    Conjugated linoleic acid (CLA) isomers, a group of positional and geometric isomers of linoleic acid [18:2(n-6)], have been studied extensively due to their ability to modulate cancer, atherosclerosis, obesity, immune function and diabetes in a variety of experimental models. The purpose of this review was to examine CLA’s isomer-specific regulation of adiposity and insulin sensitivity in humans and in cultures of human adipocytes. It has been clearly demonstrated that specific CLA isomers or...

  1. Body Composition in Adolescents with Type 1 Diabetes : Aspects of Glycaemic Control and Insulin Sensitivity

    OpenAIRE

    Särnblad, Stefan

    2004-01-01

    Excessive weight gain has frequently been reported in adolescents with type 1 diabetes, especially in girls. In general, puberty is associated with reduced insulin sensitivity that is further diminished by overweight. The causes and consequences of excessive weight gain in adolescents with type 1 diabetes are not fully understood. The studies described in this thesis addressed body composition in adolescents with type 1 diabetes and the relationships between physical activity, energy intake a...

  2. The relationship between thyrotropin and low density lipoprotein cholesterol is modified by insulin sensitivity in healthy euthyroid subjects

    NARCIS (Netherlands)

    Bakker, SJL; ter Maaten, JC; Popp-Snijders, C; Slaets, JPJ; Heine, RJ; Gans, ROB

    2001-01-01

    High levels of TSH are associated with an increased cardiovascular risk. Many cardiovascular risk factors cluster within the insulin resistance syndrome. It is not known whether levels of TSH cluster as well. We conducted this research to test the hypothesis that TSH, insulin sensitivity, and levels

  3. Adiponectin Gene Variants are Associated with Insulin Sensitivity in Response to Dietary Fat Consumption in Caucasian Men

    Science.gov (United States)

    Adiponectin (adipoQ) gene variants have been associated with type 2 diabetes mellitus and insulin resistance. Our aim was to examine whether the presence of several polymorphisms at the adipoQ gene locus (211391 G . A, 211377C.G, 45 T.G, and 276 G.T) influences the insulin sensitivity to dietary fat...

  4. Type 2 diabetes in youth: Are there racial differences in beta-cell responsiveness relative to insulin sensitivity?

    Science.gov (United States)

    Non-diabetic African American (AA) youth have an upregulated insulin secretion relative to insulin sensitivity (IS) compared with their American White (AW) peers. We investigated if similar racial differences exist in youth with T2DM. Fourteen AAs and 14 AWs T2DM adolescents underwent evaluation of ...

  5. No effect of bicarbonate treatment on insulin sensitivity and glucose control in non-diabetic older adults

    Science.gov (United States)

    Chronic mild metabolic acidosis is common among older adults, and limited evidence suggests that it may contribute to insulin resistance and type 2 diabetes. This analysis was conducted to determine whether bicarbonate supplementation, an alkalinizing treatment, improves insulin sensitivity or gluco...

  6. Effects of Insulin Sensitivity and Islet Cell Secretion Change on Glycosylated Hemoglobin in Patients with Gestational Diabetes Mellitus%妊娠期糖尿病患者胰岛素敏感性及胰岛细胞分泌变化对糖化血红蛋白的影响

    Institute of Scientific and Technical Information of China (English)

    王立红; 冯利霞; 李荣华

    2015-01-01

    目的:观察妊娠24~32周妊娠期糖尿病( GDM)患者的胰岛素敏感性以及胰岛细胞分泌变化对体内糖化血红蛋白(HbA1c)和糖化白蛋白(GA)的影响。方法选择2013年1月至2014年3月于邢台县中心医院妇产科就诊的713例妊娠妇女为研究对象,根据糖尿病诊断标准分为GDM组(243组)和非GDM组(470例),通过动态平衡模型分析稳态胰岛素评价指数(HOMA-IR)和胰岛β细胞功能指数(HOMA-β),胰岛素敏感指数(ISOGTT)和早期胰岛素分泌功能指数(ΔI0-30/ΔG0-30)。葡萄糖耐受试验( OGTT)后检测 HbA1c和GA的水平,对比两者在 GDM 患者中的应用价值。结果GDM组ISOGTT和ΔI0-30/ΔG0-30显著低于非GDM组(P<0.01),而HOMA-IR显著高于非GDM组(P<0.01)。 Pearson相关性分析表明,HbA1c与 HOMA-IR呈正相关(r =0.350,P <0.01),GA 与ΔI0-30/ΔG0-30(r=-0.219,P=0.001)和HOMA-β(r=-0.171,P=0.01)呈负相关。多因素回归分析结果显示,舒张压、空腹血糖、摄入葡萄糖120 min 血糖、HOMA-IR是 HbA1c的影响因素;空腹血糖、摄入葡萄糖120 min血糖是GA的影响因素。结论与HbA1c相比,GA与口服和餐后血糖水平显著相关,可更好地监测GDM患者胰岛素和饮食治疗的效果。%Objective To observe the secretion of insulin sensitivity and pancreatic islet cell change in pregnancy 24-32 weeks of gestation diabetes mellitus ( GDM ) patients, and the effect on the hemoglobin (HbA1c) and glycated albumin(GA).Methods A total of 713 pregnant women admitted to Xingtai Central Hospital from Jan.2011 to Mar.2012 were divided into GDM group and non-GDM group by diabetes diagnos-tic criteria.Dynamic balance model of insulin homeostasis assessment index(HOMA-IR),beta cell function (HOMA-β),insulin sensitivity index(ISOGTT) and insulin index(ΔI0-30/ΔG0-30) were measured to analyze insulin sensitivity and insulin

  7. Changes of conformation and aggregation state induced by binding of lanthanide ions to insulin

    Institute of Scientific and Technical Information of China (English)

    程驿; 李荣昌; 王夔

    2002-01-01

    To clarify the mechanism of lanthanide ions (Ln3+) on the across-membrane transport of insulin and subsequent reducing blood glucose, the interactions of Ln3+ with Zn-insulin and Zn-free insulin are investigated by spectroscopic methods. The results reveal that the binding of Ln3+ to insulin can induce its structure changes from secondary to quaternary structure, depending on the Ln3+ concentration. In the lower concentration, it triggers the conformational changes of insulin monomer in the binding region with insulin receptor (B(24-30)). It would affect insulin-insulin receptor interaction. Moreover, Ln3+ binding promotes the assembly of insulin monomer from dimer to polymer. The potency of Ln3+ in inducing insulin's aggregation is stronger than that of Zn2+. Furthermore, the aggregation can be reversed partly by EDTA-treatment, indicating that it is not due to denaturation. Similar to Zn2+ effect, Ln3+ can stabilize insulin hexamer in a certain range of concentration, but is stronger than the former.

  8. A genome-wide siRNA screen to identify modulators of insulin sensitivity and gluconeogenesis.

    Directory of Open Access Journals (Sweden)

    Ruojing Yang

    Full Text Available BACKGROUND: Hepatic insulin resistance impairs insulin's ability to suppress hepatic glucose production (HGP and contributes to the development of type 2 diabetes (T2D. Although the interests to discover novel genes that modulate insulin sensitivity and HGP are high, it remains challenging to have a human cell based system to identify novel genes. METHODOLOGY/PRINCIPAL FINDINGS: To identify genes that modulate hepatic insulin signaling and HGP, we generated a human cell line stably expressing beta-lactamase under the control of the human glucose-6-phosphatase (G6PC promoter (AH-G6PC cells. Both beta-lactamase activity and endogenous G6PC mRNA were increased in AH-G6PC cells by a combination of dexamethasone and pCPT-cAMP, and reduced by insulin. A 4-gene High-Throughput-Genomics assay was developed to concomitantly measure G6PC and pyruvate-dehydrogenase-kinase-4 (PDK4 mRNA levels. Using this assay, we screened an siRNA library containing pooled siRNA targeting 6650 druggable genes and identified 614 hits that lowered G6PC expression without increasing PDK4 mRNA levels. Pathway analysis indicated that siRNA-mediated knockdown (KD of genes known to positively or negatively affect insulin signaling increased or decreased G6PC mRNA expression, respectively, thus validating our screening platform. A subset of 270 primary screen hits was selected and 149 hits were confirmed by target gene KD by pooled siRNA and 7 single siRNA for each gene to reduce G6PC expression in 4-gene HTG assay. Subsequently, pooled siRNA KD of 113 genes decreased PEPCK and/or PGC1alpha mRNA expression thereby demonstrating their role in regulating key gluconeogenic genes in addition to G6PC. Last, KD of 61 of the above 113 genes potentiated insulin-stimulated Akt phosphorylation, suggesting that they suppress gluconeogenic gene by enhancing insulin signaling. CONCLUSIONS/SIGNIFICANCE: These results support the proposition that the proteins encoded by the genes identified in

  9. Thecal cell sensitivity to luteinizing hormone and insulin in polycystic ovarian syndrome.

    Science.gov (United States)

    Cadagan, David; Khan, Raheela; Amer, Saad

    2016-03-01

    This study examined whether a defect of steroid synthesis in ovarian theca cells may lead to the development of PCOS, through contributions to excess androgen secretion. Polycystic ovarian syndrome (PCOS) is one of the leading causes of infertility worldwide affecting around 1 in 10 of women of a reproductive age. One of the fundamental abnormalities in this syndrome is the presence of hormonal irregularities, including hyperandrogenemia, hyperinsulinemia and hypersecretion of luteinizing hormone (LH). Studies suggest that insulin treatment increases progesterone and androstenedione secretion in PCOS theca cells when compared to insulin treated normal theca cells. Furthermore the augmented effects of LH and insulin have been seen to increase ovarian androgen synthesis in non-PCOS theca cultures whilst also increasing the expression of steroidogenic enzymes specific to the PI3-K pathway. Our examination of primary thecal cultures showed an increase in both the expression of the steroidogenic enzyme CYP17 and androgen secretion in PCOS theca cells under basal conditions, when compared to non-PCOS cells. This was increased significantly under treatments of LH and insulin combined. Our results support the previous reported hypothesis that a dysfunction may exist within the PI3-K pathway. Specifically, that sensitivity exists to physiological symptoms including hyperinsulinemia and hyper secretion of LH found in PCOS through co-stimulation. The impact of these findings may allow the development of a therapeutic target in PCOS. PMID:26952754

  10. The neuronal insulin sensitizer dicholine succinate reduces stress-induced depressive traits and memory deficit: possible role of insulin-like growth factor 2

    Directory of Open Access Journals (Sweden)

    Cline Brandon H

    2012-09-01

    Full Text Available Abstract Background A number of epidemiological studies have established a link between insulin resistance and the prevalence of depression. The occurrence of depression was found to precede the onset of diabetes and was hypothesized to be associated with inherited inter-related insufficiency of the peripheral and central insulin receptors. Recently, dicholine succinate, a sensitizer of the neuronal insulin receptor, was shown to stimulate insulin-dependent H2O2 production of the mitochondrial respiratory chain leading to an enhancement of insulin receptor autophosphorylation in neurons. As such, this mechanism can be a novel target for the elevation of insulin signaling. Results Administration of DS (25 mg/kg/day, intraperitoneal in CD1 mice for 7 days prior to the onset of stress procedure, diminished manifestations of anhedonia defined in a sucrose test and behavioral despair in the forced swim test. Treatment with dicholine succinate reduced the anxiety scores of stressed mice in the dark/light box paradigm, precluded stress-induced decreases of long-term contextual memory in the step-down avoidance test and hippocampal gene expression of IGF2. Conclusions Our data suggest that dicholine succinate has an antidepressant-like effect, which might be mediated via the up-regulation of hippocampal expression of IGF2, and implicate the neuronal insulin receptor in the pathogenesis of stress-induced depressive syndrome.

  11. A sensitive chemiluminescent enzyme immunoassay for the bioanalysis of carboxyl-terminal B-chain analogues of human insulin.

    Science.gov (United States)

    Cao, Y; Smith, W C; Bowsher, R R

    2001-08-01

    Quantification of analogues of human insulin in biological matrices is complicated by differences in their immunoreactivity and the presence of both the analogue and endogenous concentrations of insulin in test samples. To facilitate pharmacokinetic comparisons of carboxyl-terminal B-chain analogues of human insulin, we undertook development of a sensitive ELISA. The ELISA detection method was optimized systematically to permit routine analysis of 10-microl serum samples. Accordingly, a noncompetitive 'sandwich' chemiluminescent ELISA was validated for the quantification of carboxyl-terminal B-chain insulin analogues in human serum over a concentration range from 5 to 3125 pM. The mean bias (RE%) within the validated range varied from -10.3 to 4.3%, with an intermediate precision (inter-assay CV%) from 4.2 to 11.5%. The two-sided 90% expectation tolerance interval for total measurement error was within +/-25% of the nominal concentration for all levels of validation samples. Insulin lispro, human insulin, proinsulin, despentapeptide insulin (DPI) and porcine insulin displayed comparable crossreactivity in the ELISA. Potential utility of the new assay for insulin bioanalysis in nonhuman species was investigated by assessing the pharmacokinetic profile of DPI in rats following administration of a single subcutaneous dose. The sensitive chemiluminescent detection method is simple to perform and should be readily adaptable for ELISAs of other therapeutic proteins.

  12. Effects of Hydroalcoholic Nettle Extract on Insulin Sensitivity and Some Inflammatory Indicator in type 2 Diabetic Patients

    Directory of Open Access Journals (Sweden)

    N. Namazi

    2012-01-01

    Full Text Available Introduction & Objective: Diabetes mellitus is a common disease that almost 1.5 million people in Iran are affected, Regarding to the adverse effects of chemical drugs, the tendency to use medicinal plants, among which nettle was chosen to be studied, is growing. In this research the effect of hydroalcoholic extract of nettle on insulin sensitivity and some inflammatory factors in type II diabetic patients were studied.Materials & Methods: A blind randomized clinical trial on 50 men and women with type 2 diabetes; (mean age: 52.39±13.75 was designed to determine the aforementioned effect. Patients were randomly divided into intervention and control groups who received 100 mg/kg, Nettle extract or placebo respectively three times a day for 8 weeks. Fasting Insulin and some inflammatory factors (Interleukin-6 (IL-6, Tumor Necrosis Factor-α (TNF-α, and hsCRP (High Sensitive C-Reactive Protein levels at the beginning and end of the study were measured. Results: IL-6 and hsCRP showed a significant decrease (P <0.05, TNF-α, insulin sensitivity and hsCRP showed no significant change at the end of the study in the intervention group compared to the control. Statistical analysis was performed with SPSS software version 18 and P <0.05 was considered significant for all measurements. Conclusion: The hydroalcoholic extract of nettle showed significant decrease in IL-6 and hsCRP after 2 months of intervention in patients with type 2 diabetes. (Sci J Hamadan Univ Med Sci 2012;18(4:10-14

  13. Prostaglandin A2 enhances cellular insulin sensitivity via a mechanism that involves the orphan nuclear receptor NR4A3.

    Science.gov (United States)

    Zhu, X; Walton, R G; Tian, L; Luo, N; Ho, S-R; Fu, Y; Garvey, W T

    2013-03-01

    We have previously reported that members of the NR4A family of orphan nuclear receptors can augment insulin's ability to stimulate glucose transport in adipocytes. In the current study, we endeavored to test for an insulin-sensitizing effect in muscle cells and to identify a potential transactivator. Lentiviral constructs were used to engineer both hyperexpression and shRNA silencing of NR4A3 in C2C12 myocytes. The NR4A3 hyper-expression construct led to a significant increase in glucose transport rates in the presence of maximal insulin while the NR4A3 knock-down exhibited a significant reduction in insulin-stimulated glucose transport rates. Consistently, insulin-mediated AKT phosphorylation was increased by NR4A3 hyperexpression and decreased following shRNA NR4A3 suppression. Then, we examined effects of prostaglandin A2 (PGA2) on insulin action and NR4A3 transactivation. PGA2 augmented insulin-stimulated glucose uptake in C2C12 myocytes and AKT phosphorylation after 12-h treatment, without significant effects on basal transport or basal AKT phosphorylation. More importantly, we demonstrated that PGA2 led to a greater improvement in insulin-stimulated glucose rates in NR4A3 overexpressing C2C12 myocytes, when compared with Lac-Z controls stimulated with insulin and PGA2. Moreover, the sensitizing effect of PGA2 was significantly diminished in NR4A3 knockdown myocytes compared to scramble controls. These results show for the first time that: (i) PGA2 augments insulin action in myocytes as manifested by enhanced stimulation of glucose transport and AKT phosphorylation; and (ii) the insulin sensitizing effect is dependent upon the orphan nuclear receptor NR4A3. PMID:23104421

  14. The Effect of Acute Exercise on Serum Vaspin Level and Its Relation to Insulin Sensitivity in Overweight Elderly Men

    OpenAIRE

    Jabbar Bashiri; Adel Rahbaran; Farhad Gholami; Sajad Ahmadizad; Saeid Nikoukheslat; Akram Moradi

    2014-01-01

    Background: Vaspin is a new discovered adipocytokine which is a member of serine protease inhibitor family secreted from adipose tissue and might play a role in insulin sensitivity. The purpose of this study was to investigate the effect of acute exercise on serum vaspin levels and its relation to insulin sensitivity in overweight elderly men. Materials and Methods: In this semi-experimental study, 12 healthy elderly men volunteers randomly selected and performed one session aerobic exerc...

  15. Alterations in whole-body insulin sensitivity resulting from repeated eccentric exercise of a single muscle group: a pilot investigation

    OpenAIRE

    Gonzalez, Javier; Barwood, Martin; Goodall, Stuart; Thomas, Kevin; Howatson, Glyn

    2015-01-01

    Unaccustomed eccentric exercise using large muscle groups elicits soreness, decrements in physical function and impairs markers of whole-body insulin sensitivity; although these effects are attenuated with a repeated exposure. Eccentric exercise of a small muscle group (elbow flexors) displays similar soreness and damage profiles in response to repeated exposure. However, it is unknown whether damage to small muscle groups impacts upon whole-body insulin sensitivity. This pilot investigation ...

  16. Are the beneficial cardiovascular effects of simvastatin and metformin also associated with a hormone-dependent mechanism improving insulin sensitivity?

    Directory of Open Access Journals (Sweden)

    C. Bulcão

    2007-02-01

    Full Text Available In addition to lipid-lowering and cardiovascular protective actions, statins may have beneficial effects on insulin sensitivity. The objective of the present study was to evaluate the effect of simvastatin therapy on insulin resistance and on leptin, adiponectin, and C-reactive protein (CRP levels, as compared to metformin, in overweight pre-diabetic subjects. Forty-one subjects with BMI >25 kg/m² and impaired fasting glucose or impaired glucose tolerance were randomized to take simvastatin, 20 mg/day (N = 20 or metformin, 1.7 g/day (N = 21 for 16 weeks. Blood samples for the determination of metabolic, hormonal, and inflammatory parameters were obtained at baseline and after each treatment. After metformin therapy, significant reductions in mean BMI and waist circumference were observed, and after simvastatin treatment LDL and triglyceride levels were significantly reduced. Insulin resistance determined by the homeostasis model assessment decreased only with metformin. Independently of the type of medication, a significant decrease in CRP levels was detected from baseline to the end of the study. CRP showed a mean reduction of 0.12 ± 0.04 mg/dL (P = 0.002 over time. No change in leptin or adiponectin levels was induced by any therapy. The data suggest that a low dose of simvastatin does not affect insulin resistance in overweight pre-diabetic subjects and has no effect on leptin or adiponectin levels. Further studies including a larger sample size, higher doses of statins, and a placebo control group are necessary to confirm the present data.

  17. Anxiety sensitivity in adolescents with somatoform autonomic dysfunction and adolescents with insulin dependent diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Pisarić Maja

    2011-01-01

    Full Text Available Anxiety sensitivity is defined as a belief that anxiety or fear may cause illness, embarrassment, or additional anxiety. The main purpose of this study was to find out if there were differences among adolescents with insulin dependent diabetes mellitus, adolescents with somatoform autonomic dysfunction and their healthy peers in different aspects of psychological functioning and anxiety sensitivity. The sample consisted of 93 subjects, aged 12 to 16. Hamburg Neuroticism and Extraversion Scale, Child Behaviour Checklist and Childhood Anxiety Sensitivity Index were administrated. The adolescents with somatoform autonomic dysfunction had significantly higher scores on neuroticism scale, different Child Behaviour Checklist subscales, and on anxiety sensitivity. Both groups with diagnosed illness had lower scores on extraversion scale compared to healthy peers. This study has shown that the adolescents with somatoform autonomic dysfunction are more prone to fears regarding bodily functioning, and that they are at a higher risk of developing an anxiety disorder.

  18. Short term low-calorie diet improves insulin sensitivity and metabolic parameters in obese women

    Directory of Open Access Journals (Sweden)

    Grazielle Vilas Bôas Huguenin

    2014-07-01

    Full Text Available Obesity and insulin resistance are associated with an increase of cardiovascular risk factors, including adipocytokines. The aim of this study was to investigate the effect of low-calorie diet on serum lipids, adipokines, insulin resistance and body composition in obese women. It was a clinical trial with class I obese women aged 30-45 years submitted to hypocaloric diet for 90 days. Dietary intake, anthropometric parameters, body composition, serum lipids, glucose, insulin, leptin, adiponectin, HOMA-IR and QUICKI indexes were evaluated at the baseline, 30, 60 and 90 days. There was 30% significant decrease in energy intake, and also decrease in body weight, body mass index and waist circumference (p < 0.01 throughout the treatment period. Despite the amount of lean body mass (kg reduced in average, it was observed that lean body mass (% had increased (p < 0.01 and that the amount of fat body mass (kg had decreased significantly in the third month (p < 0.05. Systolic blood pressure reduced up to -5mmHg (p < 0.05 after 90 days. Was observed a decrease (p < 0.05 on serum insulin and HOMA-IR until the 60th day, while the serum adiponectin increased (p < 0.01 during treatment. Corroborating with the reduction of fat body mass and weight, serum leptin also reduced (p < 0.01. These results suggest that the short-term low-calorie diet reduces total body fat, mainly found in the abdominal region, and efficiently improve insulin sensitivity decreasing cardiovascular risk in obese women.

  19. Increased fetal myocardial sensitivity to insulin-stimulated glucose metabolism during ovine fetal growth restriction.

    Science.gov (United States)

    Barry, James S; Rozance, Paul J; Brown, Laura D; Anthony, Russell V; Thornburg, Kent L; Hay, William W

    2016-04-01

    Unlike other visceral organs, myocardial weight is maintained in relation to fetal body weight in intrauterine growth restriction (IUGR) fetal sheep despite hypoinsulinemia and global nutrient restriction. We designed experiments in fetal sheep with placental insufficiency and restricted growth to determine basal and insulin-stimulated myocardial glucose and oxygen metabolism and test the hypothesis that myocardial insulin sensitivity would be increased in the IUGR heart. IUGR was induced by maternal hyperthermia during gestation. Control (C) and IUGR fetal myocardial metabolism were measured at baseline and under acute hyperinsulinemic/euglycemic clamp conditions at 128-132 days gestation using fluorescent microspheres to determine myocardial blood flow. Fetal body and heart weights were reduced by 33% (P = 0.008) and 30% (P = 0.027), respectively. Heart weight to body weight ratios were not different. Basal left ventricular (LV) myocardial blood flow per gram of LV tissue was maintained in IUGR fetuses compared to controls. Insulin increased LV myocardial blood flow by ∼38% (P flow in IUGR fetuses was 73% greater than controls. Similar to previous reports testing acute hypoxia, LV blood flow was inversely related to arterial oxygen concentration (r(2 )= 0.71) in both control and IUGR animals. Basal LV myocardial glucose delivery and uptake rates were not different between IUGR and control fetuses. Insulin increased LV myocardial glucose delivery (by 40%) and uptake (by 78%) (P < 0.01), but to a greater extent in the IUGR fetuses compared to controls. During basal and hyperinsulinemic-euglycemic clamp conditions LV myocardial oxygen delivery, oxygen uptake, and oxygen extraction efficiency were not different between groups. These novel results demonstrate that the fetal heart exposed to nutrient and oxygen deprivation from placental insufficiency appears to maintain myocardial energy supply in the IUGR condition via increased glucose uptake and

  20. Association Between Thyrotropin Levels and Insulin Sensitivity in Euthyroid Obese Adolescents

    Science.gov (United States)

    Javed, Asma; Balagopal, P. Babu; Vella, Adrian; Fischer, Philip R.; Piccinini, Francesca; Dalla Man, Chiara; Cobelli, Claudio; Giesler, Paula D.; Laugen, Jeanette M.

    2015-01-01

    Background: Thyrotropin (TSH) levels display a positive association with body mass index (BMI), and the prevalence of isolated hyperthyrotropinemia is higher in obese adolescents compared to their normal weight controls. However, the metabolic significance of the higher TSH in obese adolescents is less clear. The objective of this study was to determine the relationship between TSH concentrations and insulin sensitivity, lipids, and adipokines in euthyroid, non-diabetic, obese adolescents. Methods: Thirty-six euthyroid, non-diabetic, obese adolescents between the ages of 12 and 18 years underwent a 75 g oral glucose tolerance test. Insulin sensitivity (Si) and pancreatic β-cell function as assessed by disposition index (DI) were measured using the oral glucose minimal model approach. Cholesterol (total, low-density lipoprotein [LDL-C], and high-density lipoprotein [HDL-C]), triglycerides (TG), interleukin-6 (IL-6), total and high molecular weight (HMW) adiponectin, and retinol binding protein-4 (RBP4) were also determined. Associations between measures of thyroid function and Si, DI, lipids, and adipokines were computed using Pearson's correlation coefficient and multiple regression analysis. Results: The mean age of the subjects was 14.3±1.88 years, and the mean BMI was 32.5±4.65 kg/m2; 97% were non-Hispanic white and 47% were male. The mean TSH was 2.7±1.2 mIU/L. Increasing serum TSH was correlated with decreasing Si (log Si) in the entire cohort (p=0.03), but this relationship persisted only in males (p=0.02). The correlation between TSH and Si in males remained significant after adjusting for BMI (p=0.02). There was no correlation between TSH and pancreatic β-cell function as assessed by DI (p=0.48). TSH correlated positively with LDL-C (p=0.04) and IL-6 (p=0.03), but these associations vanished or weakened after adjusting for BMI (LDL-C p-value=0.44; IL-6 p-value=0.07). Conclusions: This study suggests a sex-specific association between TSH and insulin

  1. Effect of Feeding Status on Adjuvant Arthritis Severity, Cachexia, and Insulin Sensitivity in Male Lewis Rats

    Directory of Open Access Journals (Sweden)

    Andrea Stofkova

    2010-01-01

    Full Text Available We studied the effect of food restriction, overfeeding, and normofeeding on cachexia, inflammatory and metabolic parameters, and insulin sensitivity in chronic adjuvant arthritis (AA in rats. Food restriction during AA increased circulating ghrelin, corticosterone, decreased leptin, and ameliorated arthrogram score and systemic inflammation compared to normofeeding. Overfeeding worsened arthrogram score and systemic inflammation, and led to lipid accumulation in the liver, but not to alterations of adipokine and ghrelin plasma levels relative to normofeeding. Independently of feeding status, AA induced cachexia, in which modulation of mRNA expressions for appetite-regulating neuropeptides (NPY, AgRP, POMC, CART in the arcuate nucleus (ARC does not play a primary role. The overexpression of IL-1β mRNA in the ARC suggests its role in the mechanisms of impaired energy balance during AA under all feeding conditions. Normal HOMA index in all arthritic groups does not indicate the development of insulin resistance by feeding interventions in these rats.

  2. Targeted disruption of the CREB coactivator Crtc2 increases insulin sensitivity

    DEFF Research Database (Denmark)

    Wang, Yiguo; Inoue, Hiroshi; Ravnskjær, Kim;

    2010-01-01

    Under fasting conditions, increases in circulating concentrations of pancreatic glucagon maintain glucose homeostasis through induction of gluconeogenic genes by the CREB coactivator CRTC2. Hepatic CRTC2 activity is elevated in obesity, although the extent to which this cofactor contributes...... to attendant increases in insulin resistance is unclear. Here we show that mice with a knockout of the CRTC2 gene have decreased circulating glucose concentrations during fasting, due to attenuation of the gluconeogenic program. CRTC2 was found to stimulate hepatic gene expression in part through an N......-terminal CREB binding domain that enhanced CREB occupancy over relevant promoters in response to glucagon. Deletion of sequences encoding the CREB binding domain in CRTC2 (-/-) mice lowered circulating blood glucose concentrations and improved insulin sensitivity in the context of diet-induced obesity. Our...

  3. Changes of conformation and aggregation state induced by binding of lanthanide ions to insulin

    Institute of Scientific and Technical Information of China (English)

    程驿; 李荣昌; 王夔

    2002-01-01

    To clarify the mechanism of lanthanide ions (Ln3+) on the across-membrane transport of insulin and subsequent reducing blood glucose, the interactions of Ln3+with Zn-insulin and Zn-free insulin are investigated by spectroscopic methods. The results reveal that the binding of Ln3+ to insulin can induce its structure changes from secondary to quaternary structure, depending on the Ln3+ concentration. In the lower concentration, it triggers the conformational changes of insulin monomer in the binding region with insulin receptor (B(24-30)). It would affect insulin-insulin receptor interaction. Moreover, Ln3+ binding promotes the assembly of insulin monomer from dimer to polymer. The potency of Ln3+ in inducing insulin’s aggregation is stronger than that of Zn2+. Furthermore, the aggregation can be reversed partly by EDTA-treatment, indicating that it is not due to denaturation. Similar to Zn2+ effect, Ln3+ can stabilize insulin hexamer in a certain range of concentration, but is stronger than the former.

  4. Overfeeding Dairy Cattle During Late-Pregnancy Alters Hepatic PPARα-Regulated Pathways Including Hepatokines: Impact on Metabolism and Peripheral Insulin Sensitivity.

    Science.gov (United States)

    Khan, M Jawad; Jacometo, Carolina B; Graugnard, Daniel E; Corrêa, Marcio N; Schmitt, Eduardo; Cardoso, Felipe; Loor, Juan J

    2014-01-01

    Hepatic metabolic gene networks were studied in dairy cattle fed control (CON, 1.34 Mcal/kg) or higher energy (overfed (OVE), 1.62 Mcal/kg) diets during the last 45 days of pregnancy. A total of 57 target genes encompassing PPARα-targets/co-regulators, hepatokines, growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis, lipogenesis, and lipoprotein metabolism were evaluated on -14, 7, 14, and 30 days around parturition. OVE versus CON cows were in more negative energy balance (NEB) postpartum and had greater serum non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHBA), and liver triacylglycerol (TAG) concentrations. Milk synthesis rate did not differ. Liver from OVE cows responded to postpartal NEB by up-regulating expression of PPARα-targets in the fatty acid oxidation and ketogenesis pathways, along with gluconeogenic genes. Hepatokines (fibroblast growth factor 21 (FGF21), angiopoietin-like 4 (ANGPTL4)) and apolipoprotein A-V (APOA5) were up-regulated postpartum to a greater extent in OVE than CON. OVE led to greater blood insulin prepartum, lower NEFA:insulin, and greater lipogenic gene expression suggesting insulin sensitivity was not impaired. A lack of change in APOB, MTTP, and PNPLA3 coupled with upregulation of PLIN2 postpartum in cows fed OVE contributed to TAG accumulation. Postpartal responses in NEFA and FGF21 with OVE support a role of this hepatokine in diminishing adipose insulin sensitivity. PMID:24737933

  5. Overfeeding Dairy Cattle During Late-Pregnancy Alters Hepatic PPARα-Regulated Pathways Including Hepatokines: Impact on Metabolism and Peripheral Insulin Sensitivity

    Science.gov (United States)

    Khan, M Jawad; Jacometo, Carolina B; Graugnard, Daniel E; Corrêa, Marcio N; Schmitt, Eduardo; Cardoso, Felipe; Loor, Juan J

    2014-01-01

    Hepatic metabolic gene networks were studied in dairy cattle fed control (CON, 1.34 Mcal/kg) or higher energy (overfed (OVE), 1.62 Mcal/kg) diets during the last 45 days of pregnancy. A total of 57 target genes encompassing PPARα-targets/co-regulators, hepatokines, growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis, lipogenesis, and lipoprotein metabolism were evaluated on −14, 7, 14, and 30 days around parturition. OVE versus CON cows were in more negative energy balance (NEB) postpartum and had greater serum non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHBA), and liver triacylglycerol (TAG) concentrations. Milk synthesis rate did not differ. Liver from OVE cows responded to postpartal NEB by up-regulating expression of PPARα-targets in the fatty acid oxidation and ketogenesis pathways, along with gluconeogenic genes. Hepatokines (fibroblast growth factor 21 (FGF21), angiopoietin-like 4 (ANGPTL4)) and apolipoprotein A-V (APOA5) were up-regulated postpartum to a greater extent in OVE than CON. OVE led to greater blood insulin prepartum, lower NEFA:insulin, and greater lipogenic gene expression suggesting insulin sensitivity was not impaired. A lack of change in APOB, MTTP, and PNPLA3 coupled with upregulation of PLIN2 postpartum in cows fed OVE contributed to TAG accumulation. Postpartal responses in NEFA and FGF21 with OVE support a role of this hepatokine in diminishing adipose insulin sensitivity. PMID:24737933

  6. Role of changes in insulin and glucagon in glucose homeostasis in exercise.

    OpenAIRE

    Wolfe, R R; Nadel, E. R.; Shaw, J H; Stephenson, L A; Wolfe, M H

    1986-01-01

    This experiment was performed to determine if plasma glucose homeostasis is maintained in normal human volunteers during light exercise (40% maximal oxygen consumption [VO2 max]) when changes in insulin and glucagon are prevented. Hormonal control was achieved by the infusion of somatostatin, insulin, and glucagon. Glucose kinetics and oxidation rates were determined with stable isotopic tracers of glucose, and by indirect calorimetry. Two different rates of replacement of insulin and glucago...

  7. Molecular Dynamics Simulations of Insulin: Elucidating the Conformational Changes that Enable Its Binding.

    Directory of Open Access Journals (Sweden)

    Anastasios Papaioannou

    Full Text Available A sequence of complex conformational changes is required for insulin to bind to the insulin receptor. Recent experimental evidence points to the B chain C-terminal (BC-CT as the location of these changes in insulin. Here, we present molecular dynamics simulations of insulin that reveal new insights into the structural changes occurring in the BC-CT. We find three key results: 1 The opening of the BC-CT is inherently stochastic and progresses through an open and then a "wide-open" conformation--the wide-open conformation is essential for receptor binding, but occurs only rarely. 2 The BC-CT opens with a zipper-like mechanism, with a hinge at the Phe24 residue, and is maintained in the dominant closed/inactive state by hydrophobic interactions of the neighboring Tyr26, the critical residue where opening of the BC-CT (activation of insulin is initiated. 3 The mutation Y26N is a potential candidate as a therapeutic insulin analogue. Overall, our results suggest that the binding of insulin to its receptor is a highly dynamic and stochastic process, where initial docking occurs in an open conformation and full binding is facilitated through interactions of insulin receptor residues with insulin in its wide-open conformation.

  8. Genetic Markers of Insulin Sensitivity and Insulin Secretion Are Associated With Spontaneous Postnatal Growth and Response to Growth Hormone Treatment in Short SGA Children

    DEFF Research Database (Denmark)

    Jensen, Rikke Beck; Thankamony, Ajay; Day, Felix;

    2015-01-01

    PURPOSE: The wide heterogeneity in the early growth and metabolism of children born small for gestational age (SGA), both before and during GH therapy, may reflect common genetic variations related to insulin secretion or sensitivity. METHOD: Combined multiallele single nucleotide polymorphism sc...

  9. Effect of Candesartan Cilexetil as a Sensitive and Effective Inhibitor of SHP-1 on Insulin Signaling Pathway

    Institute of Scientific and Technical Information of China (English)

    ZHANG Lei; ZHANG Shi-tao; ZHANG Xiao-ping; SUN Jing; WANG Yong-sen; LIU Yue-long; XUE Miao-miao

    2013-01-01

    The protein tyrosine phosphatases(PTPs) comprise a family of enzymes that specifically dephosphorylate tyrosyl residues.Among them,SHP-1 has been regarded as one of the best validated intracellular tyrosine phosphatases.Downregulation of SHP-1 has shown remarkable efficacy in improving insulin sensitivity in vivo in insulin signaling pathway.In this study,we found the role of Candesartan cilexetil targeting at SHP-1.The results indicate that Candesartan cilexetil was a competitive inhibitor to SHP-1(IC50=85.6 μmol/L and Ki=24 μmol/L).We also found that Candesartan cilexetil was more sensitive towards SHP-1 compared with other PTPs.Through the consequence of Western blotting,it showed that Candesartan cilexetil can strengthen the level of tyrosine phosphorylation of several key cellular proteins[such as insulin receptor(IR),insulin receptor substrate(IRS) and ERK] in insulin signaling pathway in HepG2 cells and improve the insulin sensitivity through inhibiting the protein phosphorylation of SHP-1.These findings showed that Candesartan cilexetil might be an important inhibitor of SHP-1 and had a great application potential in the treatment of diabetes through inhibiting the level of SHP-1 in insulin signaling pathway.

  10. Insulin secretory defects in polycystic ovary syndrome. Relationship to insulin sensitivity and family history of non-insulin-dependent diabetes mellitus.

    OpenAIRE

    Ehrmann, D A; Sturis, J; Byrne, M M; Karrison, T; Rosenfield, R L; Polonsky, K S

    1995-01-01

    The increased prevalence of non-insulin-dependent diabetes mellitus (NIDDM) among women with polycystic ovary syndrome (PCOS) has been ascribed to the insulin resistance characteristic of PCOS. This study was undertaken to determine the role of defects in insulin secretion as well as familial factors to the predisposition to NIDDM seen in PCOS. We studied three groups of women: PCOS with a family history of NIDDM (PCOS FHx POS; n = 11), PCOS without a family history of NIDDM (PCOS FHx NEG; n ...

  11. The Role of Insulin, Insulin Growth Factor, and Insulin-Degrading Enzyme in Brain Aging and Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Claude Messier

    2005-01-01

    Full Text Available Most brain insulin comes from the pancreas and is taken up by the brain by what appears to be a receptor-based carrier. Type 2 diabetes animal models associated with insulin resistance show reduced insulin brain uptake and content. Recent data point to changes in the insulin receptor cascade in obesity-related insulin resistance, suggesting that brain insulin receptors also become less sensitive to insulin, which could reduce synaptic plasticity. Insulin transport to the brain is reduced in aging and in some animal models of type 2 diabetes; brain insulin resistance may be present as well. Studies examining the effect of the hyperinsulinic clamp or intranasal insulin on cognitive function have found a small but consistent improvement in memory and changes in brain neuroelectric parameters in evoked brain potentials consistent with improved attention or memory processing. These effects appear to be due to raised brain insulin levels. Peripheral levels of Insulin Growth Factor-I (IGF-I are associated with glucose regulation and influence glucose disposal. There is some indication that reduced sensitivity to insulin or IGF-I in the brain, as observed in aging, obesity, and diabetes, decreases the clearance of Aβ amyloid. Such a decrease involves the insulin receptor cascade and can also increase amyloid toxicity. Insulin and IGF-I may modulate brain levels of insulin degrading enzyme, which would also lead to an accumulation of Aβ amyloid.

  12. The effects of diet- and RYGB-induced weight loss on insulin sensitivity in obese patients with and without type 2 diabetes

    DEFF Research Database (Denmark)

    Hansen, Merethe; Lund, Michael Taulo; Jørgensen, Anne Line Kjærholm;

    2016-01-01

    AIMS: The impact of diet-induced weight loss and weight loss due to RYGB in patients with (T2DM, N = 16) and without (OB, N = 27) type 2 diabetes was studied. METHODS: At inclusion (A), after diet-induced weight loss (B), 4 months post-surgery (C) and 18 months post-surgery (D) body composition......, and approximately one-third of the total improvement in GIR in T2DM was observed after the diet-induced weight loss of only ~6 kg (B). Insulin clearance, visceral fat and fasting plasma insulin also improved significantly after the diet (P ... not change significantly, but IMTG decreased significantly consistent with significant increases in GIR. Metabolic flexibility and hepatic insulin sensitivity improved after RYGB. CONCLUSIONS: Metabolic improvements of RYGB are present already after the diet-induced weight loss prior to surgery. GLUT4...

  13. Clinical significance of changes of serum leptin and insulin levels in patients with polycystic ovary syndrome

    International Nuclear Information System (INIS)

    Objective: To explore the relationship between the serum leptin, insulin levels and development of polycystic ovary syndrome (PCOS). Methods: Serum leptin and insulin levels (with RIA) were determined in 34 patients with PCOS and 30 controls. Results: The serum leptin and insulin levels in the 34 PCOS patients were significantly higher than those in controls (P<0. 01), and those in obese patients (n=22) were significantly higher than those in non-obese ones (n=12) too(P<0.01). Conclusion: Changes of serum leptin and insulin levels were closely related to the development of PCOS and leptin might be used as a diagnostic indicator for PCOS. (authors)

  14. Insulin-sensitizing and beneficial lipid-metabolic effects of the water-soluble melanin complex extracted from Inonotus obliquus.

    Science.gov (United States)

    Lee, Jung-Han; Hyun, Chang-Kee

    2014-09-01

    Inonotus obliquus has been traditionally used for treatment of metabolic diseases; however, the mechanism remains to be elucidated. In this study, we found that the water-soluble melanin complex extracted from I. obliquus improved insulin sensitivity and reduced adiposity in high fat (HF)-fed obese mice. When the melanin complex was treated to 3T3-L1 adipocytes, insulin-stimulated glucose uptake was increased significantly, and its phosphoinositide 3-kinase-dependent action was proven with wortmannin treatment. Additionally, dose-dependent increases in Akt phosphorylation and glucose transporter 4 translocation into the plasma membrane were observed in melanin complex-treated cells. Adiponectin gene expression in 3T3-L1 cells incubated with melanin complex increased which was corroborated by increased AMP-activated protein kinase phosphorylation in HepG2 and C2C12 cells treated with conditioned media from the 3T3-L1 culture. Melanin complex-treated 3T3-L1 cells showed no significant change in expression of several lipogenic genes, whereas enhanced expressions of fatty acid oxidative genes were observed. Similarly, the epididymal adipose tissue of melanin complex-treated HF-fed mice had higher expression of fatty acid oxidative genes without significant change in lipogenic gene expression. Together, these results suggest that the water-soluble melanin complex of I. obliquus exerts antihyperglycemic and beneficial lipid-metabolic effects, making it a candidate for promising antidiabetic agent. PMID:24615848

  15. Rapid changes in plasma androgens during insulin withdrawal in male type 1 (insulin-dependent) diabetics

    DEFF Research Database (Denmark)

    Madsbad, S; Gluud, C; Bennett, Patrick;

    1986-01-01

    significant difference was found in androgen concentrations between the diabetic and the normal subjects. The normal diurnal profiles, with highest androgen concentrations in the morning before insulin withdrawal (08:00) and lowest concentrations at 20:00 h were maintained in the diabetics. However...... patients without B-cell function were more metabolically decompensated from after 4 h of insulin withdrawal compared with patients with B-cell function, no significant differences were found in androgen concentrations between the two groups although a tendency to lower concentrations were seen in the group...

  16. Beneficial effects of canagliflozin in combination with pioglitazone on insulin sensitivity in rodent models of obese type 2 diabetes.

    Directory of Open Access Journals (Sweden)

    Yoshinori Watanabe

    Full Text Available Despite its insulin sensitizing effects, pioglitazone may induce weight gain leading to an increased risk of development of insulin resistance. A novel sodium glucose co-transporter 2 (SGLT2 inhibitor, canagliflozin, provides not only glycemic control but also body weight reduction through an insulin-independent mechanism. The aim of this study was to investigate the combined effects of these agents on body weight control and insulin sensitivity.Effects of combination therapy with canagliflozin and pioglitazone were evaluated in established diabetic KK-Ay mice and prediabetic Zucker diabetic fatty (ZDF rats.In the KK-Ay mice, the combination therapy further improved glycemic control compared with canagliflozin or pioglitazone monotherapy. Furthermore, the combination significantly attenuated body weight and fat gain induced by pioglitazone and improved hyperinsulinemia. In the ZDF rats, early intervention with pioglitazone monotherapy almost completely prevented the progressive development of hyperglycemia, and no further improvement was observed by add-on treatment with canagliflozin. However, the combination significantly reduced pioglitazone-induced weight gain and adiposity and improved the Matsuda index, suggesting improved whole-body insulin sensitivity.Our study indicates that combination therapy with canagliflozin and pioglitazone improves insulin sensitivity partly by preventing glucotoxicity and, at least partly, by attenuating pioglitazone-induced body weight gain in two different obese diabetic animal models. This combination therapy may prove to be a valuable option for the treatment and prevention of obese type 2 diabetes.

  17. Trans fatty acid intake is associated with insulin sensitivity but independently of inflammation

    Directory of Open Access Journals (Sweden)

    C.T. Angelieri

    2012-07-01

    Full Text Available High saturated and trans fatty acid intake, the typical dietary pattern of Western populations, favors a proinflammatory status that contributes to generating insulin resistance (IR. We examined whether the consumption of these fatty acids was associated with IR and inflammatory markers. In this cross-sectional study, 127 non-diabetic individuals were allocated to a group without IR and 56 to another with IR, defined as homeostasis model assessment-IR (HOMA-IR >2.71. Diet was assessed using 24-h food recalls. Multiple linear regression was employed to test independent associations with HOMA-IR. The IR group presented worse anthropometric, biochemical and inflammatory profiles. Energy intake was correlated with abdominal circumference and inversely with adiponectin concentrations (r = -0.227, P = 0.002, while saturated fat intake correlated with inflammatory markers and trans fat with HOMA-IR (r = 0.160, P = 0.030. Abdominal circumference was associated with HOMA-IR (r = 0.430, P < 0.001. In multiple analysis, HOMA-IR remained associated with trans fat intake (β = 1.416, P = 0.039 and body mass index (β = 0.390, P < 0.001, and was also inversely associated with adiponectin (β = -1.637, P = 0.004. Inclusion of other nutrients (saturated fat and added sugar or other inflammatory markers (IL-6 and CRP into the models did not modify these associations. Our study supports that trans fat intake impairs insulin sensitivity. The hypothesis that its effect could depend on transcription factors, resulting in expression of proinflammatory genes, was not corroborated. We speculate that trans fat interferes predominantly with insulin signaling via intracellular kinases, which alter insulin receptor substrates.

  18. Long-term corticosterone exposure decreases insulin sensitivity and induces depressive-like behaviour in the C57BL/6NCrl mouse.

    Directory of Open Access Journals (Sweden)

    Eva L van Donkelaar

    Full Text Available Chronic stress or long-term administration of glucocorticoids disrupts the hypothalamus-pituitary-adrenal system leading to continuous high levels of glucocorticoids and insulin resistance (IR. This pre-diabetic state can eventually develop into type 2 diabetes mellitus and has been associated with a higher risk to develop depressive disorders. The mechanisms underlying the link between chronic stress, IR and depression remains unclear. The present study aimed to establish a stress-depression model in mice to further study the effects of stress-induced changes upon insulin sensitivity and behavioural consequences. A pilot study was conducted to establish the optimal administration route and a pragmatic measurement of IR. Subsequently, 6-month-old C57BL/6NCrl mice were exposed to long-term oral corticosterone treatment via the drinking water. To evaluate insulin sensitivity changes, blood glucose and plasma insulin levels were measured at different time-points throughout treatment and mice were behaviourally assessed in the elevated zero maze (EZM, forced swimming test (FST and open field test to reveal behavioural changes. Long-term corticosterone treatment increased body weight and decreased insulin sensitivity. The latter was revealed by a higher IR index and increased insulin in the plasma, whereas blood glucose levels remained unchanged. Corticosterone treatment induced longer immobility times in the FST, reflecting depressive-like behaviour. No effects were observed upon anxiety as measured in the EZM. The effect of the higher body weight of the CORT treated animals at time of testing did not influence behaviour in the EZM or FST, as no differences were found in general locomotor activity. Long-term corticosterone treatment via the drinking water reduces insulin sensitivity and induces depressive-like behaviour in the C57BL/6 mouse. This mouse model could thus be used to further explore the underlying mechanisms of chronic stress-induced T2

  19. Effect of fruit juice on glucose control and insulin sensitivity in adults: a meta-analysis of 12 randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Bin Wang

    Full Text Available BACKGROUND: Diabetes mellitus has become a worldwide health problem. Whether fruit juice is beneficial in glycemic control is still inconclusive. This study aimed to synthesize evidence from randomized controlled trials on fruit juice in relationship to glucose control and insulin sensitivity. METHODS: A strategic literature search of PubMed, EMBASE, and the Cochrane Library (updated to March, 2014 was performed to retrieve the randomized controlled trials that evaluated the effects of fruit juice on glucose control and insulin sensitivity. Study quality was assessed using the Jadad scale. Weighted mean differences were calculated for net changes in the levels of fasting glucose, fasting insulin, hemoglobin A1c (HbA1c, and homeostatic model assessment of insulin resistance (HOMA-IR using fixed- or random-effects model. Prespecified subgroup and sensitivity analyses were performed to explore the potential heterogeneity. RESULTS: Twelve trials comprising a total of 412 subjects were included in the current meta-analysis. The numbers of these studies that reported the data on fasting glucose, fasting insulin, HbA1c and HOMA-IR were 12, 5, 3 and 3, respectively. Fruit juice consumption did not show a significant effect on fasting glucose and insulin concentrations. The net change was 0.79 mg/dL (95% CI: -1.44, 3.02 mg/dL; P = 0.49 for fasting glucose concentrations and -0.74 µIU/ml (95% CI: -2.62, 1.14 µIU/ml; P = 0.44 for fasting insulin concentrations in the fixed-effects model. Subgroup analyses further suggested that the effect of fruit juice on fasting glucose concentrations was not influenced by population region, baseline glucose concentration, duration, type of fruit juice, glycemic index of fruit juice, fruit juice nutrient constitution, total polyphenols dose and Jadad score. CONCLUSION: This meta-analysis showed that fruit juice may have no overall effect on fasting glucose and insulin concentrations. More RCTs are warranted to

  20. Effect of Fruit Juice on Glucose Control and Insulin Sensitivity in Adults: A Meta-Analysis of 12 Randomized Controlled Trials

    Science.gov (United States)

    Mi, Mantian; Wang, Jian

    2014-01-01

    Background Diabetes mellitus has become a worldwide health problem. Whether fruit juice is beneficial in glycemic control is still inconclusive. This study aimed to synthesize evidence from randomized controlled trials on fruit juice in relationship to glucose control and insulin sensitivity. Methods A strategic literature search of PubMed, EMBASE, and the Cochrane Library (updated to March, 2014) was performed to retrieve the randomized controlled trials that evaluated the effects of fruit juice on glucose control and insulin sensitivity. Study quality was assessed using the Jadad scale. Weighted mean differences were calculated for net changes in the levels of fasting glucose, fasting insulin, hemoglobin A1c (HbA1c), and homeostatic model assessment of insulin resistance (HOMA-IR) using fixed- or random-effects model. Prespecified subgroup and sensitivity analyses were performed to explore the potential heterogeneity. Results Twelve trials comprising a total of 412 subjects were included in the current meta-analysis. The numbers of these studies that reported the data on fasting glucose, fasting insulin, HbA1c and HOMA-IR were 12, 5, 3 and 3, respectively. Fruit juice consumption did not show a significant effect on fasting glucose and insulin concentrations. The net change was 0.79 mg/dL (95% CI: −1.44, 3.02 mg/dL; P = 0.49) for fasting glucose concentrations and −0.74 µIU/ml (95% CI: −2.62, 1.14 µIU/ml; P = 0.44) for fasting insulin concentrations in the fixed-effects model. Subgroup analyses further suggested that the effect of fruit juice on fasting glucose concentrations was not influenced by population region, baseline glucose concentration, duration, type of fruit juice, glycemic index of fruit juice, fruit juice nutrient constitution, total polyphenols dose and Jadad score. Conclusion This meta-analysis showed that fruit juice may have no overall effect on fasting glucose and insulin concentrations. More RCTs are warranted to further

  1. Cinnamon improves insulin sensitivity and alters the body composition in an animal model of the metabolic syndrome.

    OpenAIRE

    Couturier, Karine; Batandier, Cécile; Awada, M.; Hininger-Favier, Isabelle; Canini, Frédéric; Anderson, Richard; Leverve, Xavier,; Roussel, Anne-Marie

    2010-01-01

    International audience Polyphenols from cinnamon (CN) have been described recently as insulin sensitizers and antioxidants but their effects on the glucose/insulin system in vivo have not been totally investigated. The aim of this study was to determine the effects of CN on insulin resistance and body composition, using an animal model of the metabolic syndrome, the high fat/high fructose (HF/HF) fed rat. Four groups of 22 male Wistar rats were fed for 12 weeks with: (i) (HF/HF) diet to in...

  2. Gender differences in skeletal muscle substrate metabolism - molecular mechanisms and insulin sensitivity

    Directory of Open Access Journals (Sweden)

    Anne-Marie eLundsgaard

    2014-11-01

    Full Text Available It has become increasingly apparent that substrate metabolism is subject to gender specific regulation, and the aim of this review is to outline the available evidence of molecular gender differences in glucose and lipid metabolism of skeletal muscle. Female sex has been suggested to have a favorable effect on glucose homeostasis, and the available evidence from hyperinsulinemic-euglycemic clamp studies is summarized to delineate whether there is a gender difference in whole body insulin sensitivity and in particular insulin-stimulated glucose uptake of skeletal muscle. Whether an eventual higher insulin sensitivity of female skeletal muscle can be related to gender specific regulation of molecular metabolism will be topic for discussion. Gender differences in muscle fiber type distribution and substrate availability to and in skeletal muscle are highly relevant for substrate metabolism in men and women. In particular, the molecular machinery for glucose and fatty acid oxidative and storage capacities in skeletal muscle and its implications for substrate utilization during metabolic situations of daily living are discussed, emphasizing their relevance for substrate choice in the fed and fasted state, and during periods of physical activity and recovery. Together, handling of carbohydrate and lipids and regulation of their utilization in skeletal muscle have implications for whole body glucose homeostasis in men and women. 17-β estradiol is the most important female sex hormone, and the identification of estradiol receptors in skeletal muscle has opened for a role in regulation of substrate metabolism. Also, higher levels of circulating adipokines as adiponectin and leptin in women and their implications for muscle metabolism will be considered.

  3. Beef Fat Enriched with Polyunsaturated Fatty Acid Biohydrogenation Products Improves Insulin Sensitivity Without Altering Dyslipidemia in Insulin Resistant JCR:LA-cp Rats.

    Science.gov (United States)

    Diane, Abdoulaye; Borthwick, Faye; Mapiye, Cletos; Vahmani, Payam; David, Rolland C; Vine, Donna F; Dugan, Michael E R; Proctor, Spencer D

    2016-07-01

    The main dietary sources of trans fatty acids are partially hydrogenated vegetable oils (PHVO), and products derived from polyunsaturated fatty acid biohydrogenation (PUFA-BHP) in ruminants. Trans fatty acid intake has historically been associated with negative effects on health, generating an anti-trans fat campaign to reduce their consumption. The profiles and effects on health of PHVO and PUFA-BHP can, however, be quite different. Dairy products naturally enriched with vaccenic and rumenic acids have many purported health benefits, but the putative benefits of beef fat naturally enriched with PUFA-BHP have not been investigated. The objective of the present experiment was to determine the effects of beef peri-renal fat (PRF) with differing enrichments of PUFA-BHP on lipid and insulin metabolism in a rodent model of dyslipidemia and insulin resistance (JCR:LA-cp rat). The results showed that 6 weeks of diet supplementation with beef PRF naturally enriched due to flaxseed (FS-PRF) or sunflower-seed (SS-PRF) feeding to cattle significantly improved plasma fasting insulin levels and insulin sensitivity, postprandial insulin levels (only in the FS-PRF) without altering dyslipidemia. Moreover, FS-PRF but not SS-PRF attenuated adipose tissue accumulation. Therefore, enhancing levels of PUFA-BHP in beef PRF with FS feeding may be a useful approach to maximize the health-conferring value of beef-derived fats.

  4. Beef Fat Enriched with Polyunsaturated Fatty Acid Biohydrogenation Products Improves Insulin Sensitivity Without Altering Dyslipidemia in Insulin Resistant JCR:LA-cp Rats.

    Science.gov (United States)

    Diane, Abdoulaye; Borthwick, Faye; Mapiye, Cletos; Vahmani, Payam; David, Rolland C; Vine, Donna F; Dugan, Michael E R; Proctor, Spencer D

    2016-07-01

    The main dietary sources of trans fatty acids are partially hydrogenated vegetable oils (PHVO), and products derived from polyunsaturated fatty acid biohydrogenation (PUFA-BHP) in ruminants. Trans fatty acid intake has historically been associated with negative effects on health, generating an anti-trans fat campaign to reduce their consumption. The profiles and effects on health of PHVO and PUFA-BHP can, however, be quite different. Dairy products naturally enriched with vaccenic and rumenic acids have many purported health benefits, but the putative benefits of beef fat naturally enriched with PUFA-BHP have not been investigated. The objective of the present experiment was to determine the effects of beef peri-renal fat (PRF) with differing enrichments of PUFA-BHP on lipid and insulin metabolism in a rodent model of dyslipidemia and insulin resistance (JCR:LA-cp rat). The results showed that 6 weeks of diet supplementation with beef PRF naturally enriched due to flaxseed (FS-PRF) or sunflower-seed (SS-PRF) feeding to cattle significantly improved plasma fasting insulin levels and insulin sensitivity, postprandial insulin levels (only in the FS-PRF) without altering dyslipidemia. Moreover, FS-PRF but not SS-PRF attenuated adipose tissue accumulation. Therefore, enhancing levels of PUFA-BHP in beef PRF with FS feeding may be a useful approach to maximize the health-conferring value of beef-derived fats. PMID:27072368

  5. State of the Art Review: Emerging Therapies: The Use of Insulin Sensitizers in the Treatment of Adolescents with Polycystic Ovary Syndrome (PCOS

    Directory of Open Access Journals (Sweden)

    Gordon Catherine M

    2011-08-01

    Full Text Available Abstract PCOS, a heterogeneous disorder characterized by cystic ovarian morphology, androgen excess, and/or irregular periods, emerges during or shortly after puberty. Peri- and post-pubertal obesity, insulin resistance and consequent hyperinsulinemia are highly prevalent co-morbidities of PCOS and promote an ongoing state of excess androgen. Given the relationship of insulin to androgen excess, reduction of insulin secretion and/or improvement of its action at target tissues offer the possibility of improving the physical stigmata of androgen excess by correction of the reproductive dysfunction and preventing metabolic derangements from becoming entrenched. While lifestyle changes that concentrate on behavioral, dietary and exercise regimens should be considered as first line therapy for weight reduction and normalization of insulin levels in adolescents with PCOS, several therapeutic options are available and in wide use, including oral contraceptives, metformin, thiazolidenediones and spironolactone. Overwhelmingly, the data on the safety and efficacy of these medications derive from the adult PCOS literature. Despite the paucity of randomized control trials to adequately evaluate these modalities in adolescents, their use, particularly that of metformin, has gained popularity in the pediatric endocrine community. In this article, we present an overview of the use of insulin sensitizing medications in PCOS and review both the adult and (where available adolescent literature, focusing specifically on the use of metformin in both mono- and combination therapy.

  6. FXR agonist INT-747 upregulates DDAH expression and enhances insulin sensitivity in high-salt fed Dahl rats.

    Directory of Open Access Journals (Sweden)

    Yohannes T Ghebremariam

    Full Text Available AIMS: Genetic and pharmacological studies have shown that impairment of the nitric oxide (NO synthase (NOS pathway is associated with hypertension and insulin-resistance (IR. In addition, inhibition of NOS by the endogenous inhibitor, asymmetric dimethylarginine (ADMA, may also result in hypertension and IR. On the other hand, overexpression of dimethylarginine dimethylaminohydrolase (DDAH, an enzyme that metabolizes ADMA, in mice is associated with lower ADMA, increased NO and enhanced insulin sensitivity. Since DDAH carries a farnesoid X receptor (FXR-responsive element, we aimed to upregulate its expression by an FXR-agonist, INT-747, and evaluate its effect on blood pressure and insulin sensitivity. METHODS AND RESULTS: In this study, we evaluated the in vivo effect of INT-747 on tissue DDAH expression and insulin sensitivity in the Dahl rat model of salt-sensitive hypertension and IR (Dahl-SS. Our data indicates that high salt (HS diet significantly increased systemic blood pressure. In addition, HS diet downregulated tissue DDAH expression while INT-747 protected the loss in DDAH expression and enhanced insulin sensitivity compared to vehicle controls. CONCLUSION: Our study may provide the basis for a new therapeutic approach for IR by modulating DDAH expression and/or activity using small molecules.

  7. Relationships of serum soluble E-selectin concentration with insulin sensitivity and metabolic flexibility in lean and obese women.

    Science.gov (United States)

    Adamska, Agnieszka; Karczewska-Kupczewska, Monika; Nikołajuk, Agnieszka; Otziomek, Elżbieta; Górska, Maria; Kowalska, Irina; Strączkowski, Marek

    2014-04-01

    The markers of endothelial dysfunction, including soluble E-selectin (sE-selectin), are related to insulin resistance, which is associated with metabolic inflexibility, i.e., impaired stimulation of carbohydrate oxidation and impaired inhibition of lipid oxidation by insulin. Endothelial dysfunction may also be important in the metabolic syndrome. The aim of our study was to analyze the association of sE-selectin with insulin sensitivity and metabolic flexibility in lean and obese women. We examined 22 lean women (BMI 25 kg m(-2)) with normal glucose tolerance. A hyperinsulinemic euglycemic clamp and indirect calorimetry were performed. An increase in the respiratory exchange ratio in response to insulin was used as a measure of metabolic flexibility. Obese women had lower insulin sensitivity (P metabolic syndrome total Z-score (MS Z-score) (P metabolic flexibility (r = -0.34, P = 0.003). MS Z-score correlated positively with sE-selectin level and negatively with metabolic flexibility and insulin sensitivity (r = 0.49, P metabolic flexibility and sE-selectin (β = -0.36; P = 0.004) was independent of the other evaluated factors. Our data suggest that endothelial dysfunction as assessed by plasma sE-selectin is associated with metabolic flexibility, inversely and independently of the other estimated factors. PMID:23934358

  8. MsrA Overexpression Targeted to the Mitochondria, but Not Cytosol, Preserves Insulin Sensitivity in Diet-Induced Obese Mice.

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    JennaLynn Hunnicut

    Full Text Available There is growing evidence that oxidative stress plays an integral role in the processes by which obesity causes type 2 diabetes. We previously identified that mice lacking the protein oxidation repair enzyme methionine sulfoxide reductase A (MsrA are particularly prone to obesity-induced insulin resistance suggesting an unrecognized role for this protein in metabolic regulation. The goals of this study were to test whether increasing the expression of MsrA in mice can protect against obesity-induced metabolic dysfunction and to elucidate the potential underlying mechanisms. Mice with increased levels of MsrA in the mitochondria (TgMito MsrA or in the cytosol (TgCyto MsrA were fed a high fat/high sugar diet and parameters of glucose homeostasis were monitored. Mitochondrial content, markers of mitochondrial proteostasis and mitochondrial energy utilization were assessed. TgMito MsrA, but not TgCyto MsrA, mice remain insulin sensitive after high fat feeding, though these mice are not protected from obesity. This metabolically healthy obese phenotype of TgMito MsrA mice is not associated with changes in mitochondrial number or biogenesis or with a reduction of proteostatic stress in the mitochondria. However, our data suggest that increased mitochondrial MsrA can alter metabolic homeostasis under diet-induced obesity by activating AMPK signaling, thereby defining a potential mechanism by which this genetic alteration can prevent insulin resistance without affecting obesity. Our data suggest that identification of targets that maintain and regulate the integrity of the mitochondrial proteome, particular against oxidative damage, may play essential roles in the protection against metabolic disease.

  9. Cinnamon counteracts the negative effects of a high fat/high fructose diet on behavior, brain insulin signaling and Alzheimer-associated changes.

    Directory of Open Access Journals (Sweden)

    Richard A Anderson

    Full Text Available Insulin resistance leads to memory impairment. Cinnamon (CN improves peripheral insulin resistance but its effects in the brain are not known. Changes in behavior, insulin signaling and Alzheimer-associated mRNA expression in the brain were measured in male Wistar rats fed a high fat/high fructose (HF/HFr diet to induce insulin resistance, with or without CN, for 12 weeks. There was a decrease in insulin sensitivity associated with the HF/HFr diet that was reversed by CN. The CN fed rats were more active in a Y maze test than rats fed the control and HF/HFr diets. The HF/HFr diet fed rats showed greater anxiety in an elevated plus maze test that was lessened by feeding CN. The HF/HFr diet also led to a down regulation of the mRNA coding for GLUT1 and GLUT3 that was reversed by CN in the hippocampus and cortex. There were increases in Insr, Irs1 and Irs2 mRNA in the hippocampus and cortex due to the HF/HFr diet that were not reversed by CN. Increased peripheral insulin sensitivity was also associated with increased glycogen synthase in both hippocampus and cortex in the control and HF/HFr diet animals fed CN. The HF/HFr diet induced increases in mRNA associated with Alzheimers including PTEN, Tau and amyloid precursor protein (App were also alleviated by CN. In conclusion, these data suggest that the negative effects of a HF/HFr diet on behavior, brain insulin signaling and Alzheimer-associated changes were alleviated by CN suggesting that neuroprotective effects of CN are associated with improved whole body insulin sensitivity and related changes in the brain.

  10. Replacing Fish Oil with Vegetable Oils in Salmon Feed Increases Hepatic Lipid Accumulation and Reduces Insulin Sensitivity in Mice

    DEFF Research Database (Denmark)

    Midtbø, Lisa Kolden

    levels of diacylglycerol (DAG), ceramides and arachidonic acid (AA)-derived oxylipins compared with mice fed WD-FO. In addition, C57BL/6J mice were fed fish oil-enriched diets with different carbohydrate sources, and we observed that sucrose dose-dependently abrogate the antiobesity effect of fish oil....... High-GI starch had a stronger effect on reducing the antiobesity effect of FO compared with low-GI starch. Conclusions: In summary, our results demonstrate that the background diet affects the antiobesity effect of FO and that replacement of FO with SO in aqua feed increased hepatic lipid accumulation...... these changes affects obesity development and insulin sensitivity in mice eating the salmon. In addition, we wanted to investigate how the background diet affects the antiobesity effect of FO. Results: Western diets (WDs) were produced containing salmon fed either FO (WD-FO), or with partly replacement (80...

  11. Involvement of insulin-degrading enzyme in insulin- and atrial natriuretic peptide-sensitive internalization of amyloid-β peptide in mouse brain capillary endothelial cells.

    Science.gov (United States)

    Ito, Shingo; Ohtsuki, Sumio; Murata, Sho; Katsukura, Yuki; Suzuki, Hiroya; Funaki, Miho; Tachikawa, Masanori; Terasaki, Tetsuya

    2014-01-01

    Cerebral clearance of amyloid-β peptide (Aβ), which is implicated in Alzheimer's disease, involves elimination across the blood-brain barrier (BBB), and we previously showed that an insulin-sensitive process is involved in the case of Aβ1-40. The purpose of this study was to clarify the molecular mechanism of the insulin-sensitive Aβ1-40 elimination across mouse BBB. An in vivo cerebral microinjection study demonstrated that [125I]hAβ1-40 elimination from mouse brain was inhibited by human natriuretic peptide (hANP), and [125I]hANP elimination was inhibited by hAβ1-40, suggesting that hAβ1-40 and hANP share a common elimination process. Internalization of [125I]hAβ1-40 into cultured mouse brain capillary endothelial cells (TM-BBB4) was significantly inhibited by either insulin, hANP, other natriuretic peptides or insulin-degrading enzyme (IDE) inhibitors, but was not inhibited by phosphoramidon or thiorphan. Although we have reported the involvement of natriuretic peptide receptor C (Npr-C) in hANP internalization, cells stably expressing Npr-C internalized [125I]hANP but not [125I]hAβ1-40, suggesting that there is no direct interaction between Npr-C and hAβ1-40. IDE was detected in plasma membrane of TM-BBB4 cells, and internalization of [125I]hAβ1-40 by TM-BBB4 cells was reduced by IDE-targeted siRNAs. We conclude that elimination of hAβ1-40 from mouse brain across the BBB involves an insulin- and ANP-sensitive process, mediated by IDE expressed in brain capillary endothelial cells.

  12. Dietary intervention increases n-3 long-chain polyunsaturated fatty acids in skeletal muscle membrane phospholipids of obese subjects. Implications for insulin sensitivity

    DEFF Research Database (Denmark)

    Haugaard, S.B.; Madsbad, S.; Høy, Carl-Erik;

    2006-01-01

    analysis that included changes in weight, fat mass, waist circumference, plasma lipids, PUFA, SFA and long-chain PUFAn-3 indicated that SFA and long-chain PUFAn-3 were independent predictors of HOMA-IR (R-2 = 0.33, P ...Objective Cross-sectional studies suggest that the fatty acid (FA) composition of phospholipids in skeletal muscle cell membrane may modulate insulin sensitivity in humans. We examined the impact of a hypocaloric low-fat dietary intervention on membrane FA composition and insulin sensitivity....... Design Muscle membrane FA profiles were determined in muscle (vastus lateralis) biopsies from 21 obese subjects before and after 6 months of dietary restriction. Diet instructions emphasized low intake of FA of marine origin by recommending lean fish and prohibiting fatty fish and fish oil supplements...

  13. Dietary intervention increases n-3 long-chain polyunsaturated fatty acids in sceletal muscle membrane phospholipids of obese subjects. Inplications for insulin sensitivity

    DEFF Research Database (Denmark)

    Haugaard, Steen B; Madsbad, Sten; Høy, C-E;

    2006-01-01

    that included changes in weight, fat mass, waist circumference, plasma lipids, PUFA, SFA and long-chain PUFAn-3 indicated that SFA and long-chain PUFAn-3 were independent predictors of HOMA-IR (R(2)=0.33, P...OBJECTIVE: Cross-sectional studies suggest that the fatty acid (FA) composition of phospholipids in skeletal muscle cell membrane may modulate insulin sensitivity in humans. We examined the impact of a hypocaloric low-fat dietary intervention on membrane FA composition and insulin sensitivity....... DESIGN Muscle membrane FA profiles were determined in muscle (vastus lateralis) biopsies from 21 obese subjects before and after 6 months of dietary restriction. Diet instructions emphasized low intake of FA of marine origin by recommending lean fish and prohibiting fatty fish and fish oil supplements...

  14. The Relationship between Adiposity and Insulin Sensitivity in African Women Living with the Polycystic Ovarian Syndrome: A Clamp Study

    Science.gov (United States)

    Dohbit, Sama; Tchana-Sinou, Mycilline; Foumane, Pascal; Donfack, Olivier Trésor; Doh, Anderson S.

    2016-01-01

    Objectives. We aimed to assess the variation of insulin sensitivity in relation to obesity in women living with PCOS in a sub-Sahara African setting. Methods. We studied body composition, insulin sensitivity, and resting energy expenditure in 14 PCOS patients (6 obese and 8 nonobese) compared to 10 matched nonobese non-PCOS subjects. Insulin sensitivity was assessed using the gold standard 80 mU/m2/min euglycemic-hyperinsulinemic clamp and resting energy expenditure was measured by indirect calorimetry. Results. Insulin sensitivity adjusted to lean mass was lowest in obese PCOS subjects and highest in healthy subjects (11.2 [10.1–12.4] versus 12.9 [12.1–13.8] versus 16.6 [13.8–17.9], p = 0.012); there was a tendency for resting energy expenditure adjusted for total body mass to decrease across the groups highest in obese PCOS subjects (1411 [1368–1613] versus 1274 [1174–1355] versus 1239 [1195–1454], p = 0.306). Conclusion. In this sub-Saharan population, insulin resistance is associated with PCOS per se but is further aggravated by obesity. Obesity did not seem to be explained by low resting energy expenditure suggesting that dietary intake may be a determinant of the obesity in this context. PMID:27672393

  15. Coordinate Transcriptomic and Metabolomic Effects of the Insulin Sensitizer Rosiglitazone on Fundamental Metabolic Pathways in Liver, Soleus Muscle, and Adipose Tissue in Diabetic db/db Mice

    Directory of Open Access Journals (Sweden)

    Sabrina Le Bouter

    2010-01-01

    Full Text Available Rosiglitazone (RSG, developed for the treatment of type 2 diabetes mellitus, is known to have potent effects on carbohydrate and lipid metabolism leading to the improvement of insulin sensitivity in target tissues. To further assess the capacity of RSG to normalize gene expression in insulin-sensitive tissues, we compared groups of 18-day-treated db/db mice with increasing oral doses of RSG (10, 30, and 100 mg/kg/d with untreated non-diabetic littermates (db/+. For this aim, transcriptional changes were measured in liver, inguinal adipose tissue (IAT and soleus muscle using microarrays and real-time PCR. In parallel, targeted metabolomic assessment of lipids (triglycerides (TGs and free fatty acids (FFAs in plasma and tissues was performed by UPLC-MS methods. Multivariate analyses revealed a relationship between the differential gene expressions in liver and liver trioleate content and between blood glucose levels and a combination of differentially expressed genes measured in liver, IAT, and muscle. In summary, we have integrated gene expression and targeted metabolomic data to present a comprehensive overview of RSG-induced changes in a diabetes mouse model and improved the molecular understanding of how RSG ameliorates diabetes through its effect on the major insulin-sensitive tissues.

  16. Expression and regulation of facilitative glucose transporters in equine insulin-sensitive tissue: from physiology to pathology.

    Science.gov (United States)

    Lacombe, Véronique A

    2014-01-01

    Glucose uptake is the rate-limiting step in glucose utilization in mammalians and is tightly regulated by a family of specialized proteins, called the facilitated glucose transporters (GLUTs/SLC2). GLUT4, the major isoform in insulin-responsive tissue, translocates from an intracellular pool to the cell surface and as such determines insulin-stimulated glucose uptake. However, despite intensive research over 50 years, the insulin-dependent and -independent pathways that mediate GLUT4 translocation are not fully elucidated in any species. Insulin resistance (IR) is one of the hallmarks of equine metabolic syndrome and is the most common metabolic predisposition for laminitis in horses. IR is characterized by the impaired ability of insulin to stimulate glucose disposal into insulin-sensitive tissues. Similar to other species, the functional capability of the insulin-responsive GLUTs is impaired in muscle and adipose tissue during IR in horses. However, the molecular mechanisms of altered glucose transport remain elusive in all species, and there is still much to learn about the physiological and pathophysiological functions of the GLUT family members, especially in regard to class III. Since GLUTs are key regulators of whole-body glucose homeostasis, they have received considerable attention as potential therapeutic targets to treat metabolic disorders in human and equine patients. PMID:24977043

  17. Preventing High Fat Diet-induced Obesity and Improving Insulin Sensitivity through Neuregulin 4 Gene Transfer.

    Science.gov (United States)

    Ma, Yongjie; Gao, Mingming; Liu, Dexi

    2016-01-01

    Neuregulin 4 (NRG4), an epidermal growth factor-like signaling molecule, plays an important role in cell-to-cell communication during tissue development. Its function to regulate energy metabolism has recently been reported. This current study was designed to assess the preventive and therapeutic effects of NRG4 overexpression on high fat diet (HFD)-induced obesity. Using the hydrodynamic gene transfer method, we demonstrate that Nrg4 gene transfer in mice suppressed the development of diet-induced obesity, but did not affect pre-existing adiposity and body weight in obese mice. Nrg4 gene transfer curbed HFD-induced hepatic steatosis by inhibiting lipogenesis and PPARγ-mediated lipid storage. Concurrently, overexpression of NRG4 reduced chronic inflammation in both preventive and treatment studies, evidenced by lower mRNA levels of macrophage marker genes including F4/80, Cd68, Cd11b, Cd11c, and macrophage chemokine Mcp1, resulting in improved insulin sensitivity. Collectively, these results demonstrate that overexpression of the Nrg4 gene by hydrodynamic gene delivery prevents HFD-induced weight gain and fatty liver, alleviates obesity-induced chronic inflammation and insulin resistance, and supports the health benefits of NRG4 in managing obesity and obesity-associated metabolic disorders. PMID:27184920

  18. Characterization of lipid metabolism in insulin-sensitive adipocytes differentiated from immortalized human mesenchymal stem cells

    International Nuclear Information System (INIS)

    There is a great demand for cell models to study human adipocyte function. Here we describe the adipogenic differentiation of a telomerase-immortalized human mesenchymal stem cell line (hMSC-Tert) that maintains numerous features of terminally differentiated adipocytes even after prolonged withdrawal of the peroxisome proliferator activated receptor γ (PPARγ) agonist rosiglitazone. Differentiated hMSC-Tert developed the characteristic monolocular phenotype of mature adipocytes. The expression of adipocyte specific markers was highly increased during differentiation. Most importantly, the presence of the PPARγ agonist rosiglitazone was not required for the stable expression of lipoprotein lipase, adipocyte fatty acid binding protein and perilipin on mRNA and protein levels. Adiponectin expression was post-transcriptionally down-regulated in the absence of rosiglitazone. Insulin sensitivity as measured by insulin-induced phosphorylation of Akt and S6 ribosomal protein was also independent of rosiglitazone. In addition to commonly used adipogenic markers, we investigated further PPARγ-stimulated proteins with a role in lipid metabolism. We observed an increase of lipoprotein receptor (VLDLR, LRP1) and apolipoprotein E expression during differentiation. Despite this increased expression, the receptor-mediated endocytosis of lipoproteins was decreased in differentiated adipocytes, suggesting that these proteins may have an additional function in adipose tissue beyond lipoprotein uptake

  19. The novel ATP-sensitive potassium channel opener iptakalim prevents insulin resistance associated with hypertension via restoring endothelial function

    Institute of Scientific and Technical Information of China (English)

    Yu WANG; Fu-hu ZENG; Chao-liang LONG; Zhi-yuan PAN; Wen-yu CUI; Ru-huan WANG; Guo-shu LIU; Hai WANG

    2011-01-01

    To investigate the effects of iptakalim on endothelial dysfunction induced by insulin resistance (IR) and to determine whether iptakalim improved IR associated with hypertension in fructose-fed rats (FFRs) and spontaneously hypertensive rats (SHRs).Methods:Human umbilical vein endothelial cells (HUVECs) were used for in vitro study.The levels of endothelial vasoactive mediators and eNOS protein expression were determined using radioimmunoassays,ELISAs,colorimetric assays or Western blotting.Sprague-Dawley rats were fed with a high-fructose diet.In both FFRs and SHRs,tail-cuff method was used to measure systolic blood pressure (SBP),and hyperinsulinemic-euglycemic clamp was used to evaluate IR states.Results:(1) Cultured HUVECs incubated with the PI3-kinase inhibitor wortmannin (50 nmol/L) and insulin (100 nmol/L) induced endothelial dysfunction characterized by significantly reduced release of NO and expression of eNOS protein,and significantly increased production of ET-1.Pretreatment with iptakalim (0.1-10 μmol/L) could prevent the endothelial dysfunction.(2) In FFRs,the levels of SBP,fasting plasma glucose and insulin were significantly elevated,whereas the glucose infusion rate (GIR) and insulin sensitive index (ISI) were significantly decreased,and the endothelium-dependent vascular relaxation response to ACh was impaired.These changes could be prevented by oral administration of iptakalim (1,3,or 9 mg-kg-1-d-1,for 4 weeks).The imbalance between serum NO and ET-1 was also ameliorated by iptakalim.(3) In 2-4 month-old SHRs (IR was established at the age of 4 months),oral administration of iptakalim (1,3,or 9 mg.kg-1.d-1,for 8 weeks) significantly ameliorated hypertension and increased the GIR to the normal level.Conclusion:These results demonstrate that iptakalim could protect against IR-induced endothelial dysfunction,and ameliorate IR associated with hypertension,possibly via restoring the balance between NO and ET-1 signaling.

  20. Adipose tissue dysregulation and reduced insulin sensitivity in non-obese individuals with enlarged abdominal adipose cells

    Directory of Open Access Journals (Sweden)

    Hammarstedt Ann

    2012-09-01

    Full Text Available Abstract Background Obesity contributes to Type 2 diabetes by promoting systemic insulin resistance. Obesity causes features of metabolic dysfunction in the adipose tissue that may contribute to later impairments of insulin action in skeletal muscle and liver; these include reduced insulin-stimulated glucose transport, reduced expression of GLUT4, altered expression of adipokines, and adipocyte hypertrophy. Animal studies have shown that expansion of adipose tissue alone is not sufficient to cause systemic insulin resistance in the absence of adipose tissue metabolic dysfunction. To determine if this holds true for humans, we studied the relationship between insulin resistance and markers of adipose tissue dysfunction in non-obese individuals. Method 32 non-obese first-degree relatives of Type 2 diabetic patients were recruited. Glucose tolerance was determined by an oral glucose tolerance test and insulin sensitivity was measured with the hyperinsulinaemic-euglycaemic clamp. Blood samples were collected and subcutaneous abdominal adipose tissue biopsies obtained for gene/protein expression and adipocyte cell size measurements. Results Our findings show that also in non-obese individuals low insulin sensitivity is associated with signs of adipose tissue metabolic dysfunction characterized by low expression of GLUT4, altered adipokine profile and enlarged adipocyte cell size. In this group, insulin sensitivity is positively correlated to GLUT4 mRNA (R = 0.49, p = 0.011 and protein (R = 0.51, p = 0.004 expression, as well as with circulating adiponectin levels (R = 0.46, 0 = 0.009. In addition, insulin sensitivity is inversely correlated to circulating RBP4 (R = −0.61, 0 = 0.003 and adipocyte cell size (R = −0.40, p = 0.022. Furthermore, these features are inter-correlated and also associated with other clinical features of the metabolic syndrome in the absence of obesity. No association could be found

  1. IGF-I bioactivity in an elderly population: Relation to insulin sensitivity, insulin levels, and the metabolic syndrome

    NARCIS (Netherlands)

    M.P. Brugts (Michael); C.M. van Duijn (Cock); L.J. Hofland (Leo); J.C.M. Witteman (Jacqueline); S.W.J. Lamberts (Steven); J.A.M.J.L. Janssen (Joop)

    2010-01-01

    textabstractOBJECTIVE - There is a complex relationship between IGF-I, IGF binding proteins, growth hormone, and insulin. The IGF-I kinase receptor activation assay (KIRA) is a novel method for measuring IGF-I bioactivity in human serum. We speculated that determination of IGF-I bioactivity might br

  2. The changes in levels of C-P and insulin in glucose tolerance test in rats with experimental non-insulin dependent diabetes mellitus

    International Nuclear Information System (INIS)

    The changes in levels of C-P and insulin were investigated in the GT test in rats with non-insulin dependent diabetes mellitus. In order to establish a model of non-insulin dependent diabetes mellitus (NIDDM), the authors injected rats with small dose streptozocoi (i.v.). Two weeks after the injection, the rats developed impaired glucose tolerance (IGT). Then, they were fed with high energy diet for eight weeks to form NIDDM. The results showed that the highest peak time of C-P and insulin in NIDDM was remarkably later than that in normal subjects, the highest peak time was in two hours (P < 0.05). The data suggest that level of C-P could accurately respond to level of insulin, and this experimental non-insulin dependent diabetes mellitus model is ideal

  3. A PPARγ-Bnip3 Axis Couples Adipose Mitochondrial Fusion-Fission Balance to Systemic Insulin Sensitivity.

    Science.gov (United States)

    Tol, Marc J; Ottenhoff, Roelof; van Eijk, Marco; Zelcer, Noam; Aten, Jan; Houten, Sander M; Geerts, Dirk; van Roomen, Cindy; Bierlaagh, Marlou C; Scheij, Saskia; Hoeksema, Marten A; Aerts, Johannes M; Bogan, Jonathan S; Dorn, Gerald W; Argmann, Carmen A; Verhoeven, Arthur J

    2016-09-01

    Aberrant mitochondrial fission plays a pivotal role in the pathogenesis of skeletal muscle insulin resistance. However, fusion-fission dynamics are physiologically regulated by inherent tissue-specific and nutrient-sensitive processes that may have distinct or even opposing effects with respect to insulin sensitivity. Based on a combination of mouse population genetics and functional in vitro assays, we describe here a regulatory circuit in which peroxisome proliferator-activated receptor γ (PPARγ), the adipocyte master regulator and receptor for the thiazolidinedione class of antidiabetic drugs, controls mitochondrial network fragmentation through transcriptional induction of Bnip3. Short hairpin RNA-mediated knockdown of Bnip3 in cultured adipocytes shifts the balance toward mitochondrial elongation, leading to compromised respiratory capacity, heightened fatty acid β-oxidation-associated mitochondrial reactive oxygen species generation, insulin resistance, and reduced triacylglycerol storage. Notably, the selective fission/Drp1 inhibitor Mdivi-1 mimics the effects of Bnip3 knockdown on adipose mitochondrial bioenergetics and glucose disposal. We further show that Bnip3 is reciprocally regulated in white and brown fat depots of diet-induced obesity and leptin-deficient ob/ob mouse models. Finally, Bnip3(-/-) mice trade reduced adiposity for increased liver steatosis and develop aggravated systemic insulin resistance in response to high-fat feeding. Together, our data outline Bnip3 as a key effector of PPARγ-mediated adipose mitochondrial network fragmentation, improving insulin sensitivity and limiting oxidative stress. PMID:27325287

  4. Hyperandrogenism and Insulin Resistance, Not Changes in Body Weight, Mediate the Development of Endothelial Dysfunction in a Female Rat Model of Polycystic Ovary Syndrome (PCOS).

    Science.gov (United States)

    Hurliman, Amanda; Keller Brown, Jennifer; Maille, Nicole; Mandala, Maurizio; Casson, Peter; Osol, George

    2015-11-01

    This study was designed to differentiate the contributions of hyperandrogenism, insulin resistance (IR), and body weight to the development of endothelial dysfunction in polycystic ovary syndrome and determine the effectiveness of insulin sensitization and antiandrogenic therapy after the establishment of vascular and metabolic dysfunction using a rat model of polycystic ovary syndrome. We hypothesized that the observed endothelial dysfunction was a direct steroidal effect, as opposed to changes in insulin sensitivity or body weight. Prepubertal female rats were randomized to the implantation of a pellet containing DHT or sham procedure. In phase 1, DHT-exposed animals were randomized to pair feeding to prevent weight gain or metformin, an insulin-sensitizing agent, from 5 to 14 weeks. In phase 2, DHT-exposed animals were randomized to treatment with metformin or flutamide, a nonsteroidal androgen receptor blocker from 12 to 16 weeks. Endothelial function was assessed by the vasodilatory response of preconstricted arteries to acetylcholine. Serum steroid levels were analyzed in phase 1 animals. Fasting blood glucose and plasma insulin were analyzed and homeostasis model assessment index calculated in all animals. Our data confirm the presence of endothelial dysfunction as well as increased body weight, hypertension, hyperinsulinemia, and greater IR among DHT-treated animals. Even when normal weight was maintained through pair feeding, endothelial dysfunction, hyperinsulinemia, and IR still developed. Furthermore, despite weight gain, treatment with metformin and flutamide improved insulin sensitivity and blood pressure and restored normal endothelial function. Therefore, the observed endothelial dysfunction is most likely a direct result of hyperandrogenism-induced reductions in insulin sensitivity, as opposed to weight gain.

  5. Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity

    DEFF Research Database (Denmark)

    Vrieze, Anne; Out, Carolien; Fuentes, Susana;

    2014-01-01

    in humans would affect fecal microbiota composition and subsequently bile acid and glucose metabolism. METHODS: In this single blinded randomized controlled trial, 20 male obese subjects with metabolic syndrome were randomized to 7 days of amoxicillin 500 mg t.i.d. or 7 days of vancomycin 500 mg t.......i.d. At baseline and after 1 week of therapy, fecal microbiota composition (Human Intestinal Tract Chip phylogenetic microarray), fecal and plasma bile acid concentrations as well as insulin sensitivity (hyperinsulinemic euglycemic clamp using [6,6-(2)H2]-glucose tracer) were measured. RESULTS: Vancomycin reduced...... fecal microbial diversity with a decrease of gram-positive bacteria (mainly Firmicutes) and a compensatory increase in gram-negative bacteria (mainly Proteobacteria). Concomitantly, vancomycin decreased fecal secondary bile acids with a simultaneous postprandial increase in primary bile acids in plasma...

  6. Pioglitazone improves fat distribution, the adipokine profile and hepatic insulin sensitivity in non-diabetic end-stage renal disease subjects on maintenance dialysis: a randomized cross-over pilot study.

    Directory of Open Access Journals (Sweden)

    Anne Zanchi

    Full Text Available BACKGROUND: Fat redistribution, increased inflammation and insulin resistance are prevalent in non-diabetic subjects treated with maintenance dialysis. The aim of this study was to test whether pioglitazone, a powerful insulin sensitizer, alters body fat distribution and adipokine secretion in these subjects and whether it is associated with improved insulin sensitivity. TRIAL DESIGN: This was a double blind cross-over study with 16 weeks of pioglitazone 45 mg vs placebo involving 12 subjects. METHODS: At the end of each phase, body composition (anthropometric measurements, dual energy X-ray absorptometry (DEXA, abdominal CT, hepatic and muscle insulin sensitivity (2-step hyperinsulinemic euglycemic clamp with 2H2-glucose were measured and fasting blood adipokines and cardiometabolic risk markers were monitored. RESULTS: Four months treatment with pioglitazone had no effect on total body weight or total fat but decreased the visceral/sub-cutaneous adipose tissue ratio by 16% and decreased the leptin/adiponectin (L/A ratio from 3.63 × 10(-3 to 0.76 × 10(-3. This was associated with a 20% increase in hepatic insulin sensitivity without changes in muscle insulin sensitivity, a 12% increase in HDL cholesterol and a 50% decrease in CRP. CONCLUSIONS/LIMITATIONS: Pioglitazone significantly changes the visceral-subcutaneous fat distribution and plasma L/A ratio in non diabetic subjects on maintenance dialysis. This was associated with improved hepatic insulin sensitivity and a reduction of cardio-metabolic risk markers. Whether these effects may improve the outcome of non diabetic end-stage renal disease subjects on maintenance dialysis still needs further evaluation. TRIAL REGISTRATION: ClinicalTrial.gov NCT01253928.

  7. Pioglitazone Improves Fat Distribution, the Adipokine Profile and Hepatic Insulin Sensitivity in Non-Diabetic End-Stage Renal Disease Subjects on Maintenance Dialysis: A Randomized Cross-Over Pilot Study

    Science.gov (United States)

    Zanchi, Anne; Tappy, Luc; Lê, Kim-Anne; Bortolotti, Murielle; Theumann, Nicolas; Halabi, Georges; Gauthier, Thierry; Mathieu, Claudine; Tremblay, Sylvie; Bertrand, Pauline Coti; Burnier, Michel; Teta, Daniel

    2014-01-01

    Background Fat redistribution, increased inflammation and insulin resistance are prevalent in non-diabetic subjects treated with maintenance dialysis. The aim of this study was to test whether pioglitazone, a powerful insulin sensitizer, alters body fat distribution and adipokine secretion in these subjects and whether it is associated with improved insulin sensitivity. Trial Design This was a double blind cross-over study with 16 weeks of pioglitazone 45 mg vs placebo involving 12 subjects. Methods At the end of each phase, body composition (anthropometric measurements, dual energy X-ray absorptometry (DEXA), abdominal CT), hepatic and muscle insulin sensitivity (2-step hyperinsulinemic euglycemic clamp with 2H2-glucose) were measured and fasting blood adipokines and cardiometabolic risk markers were monitored. Results Four months treatment with pioglitazone had no effect on total body weight or total fat but decreased the visceral/sub-cutaneous adipose tissue ratio by 16% and decreased the leptin/adiponectin (L/A) ratio from 3.63×10−3 to 0.76×10−3. This was associated with a 20% increase in hepatic insulin sensitivity without changes in muscle insulin sensitivity, a 12% increase in HDL cholesterol and a 50% decrease in CRP. Conclusions/Limitations Pioglitazone significantly changes the visceral-subcutaneous fat distribution and plasma L/A ratio in non diabetic subjects on maintenance dialysis. This was associated with improved hepatic insulin sensitivity and a reduction of cardio-metabolic risk markers. Whether these effects may improve the outcome of non diabetic end-stage renal disease subjects on maintenance dialysis still needs further evaluation. Trial Registration ClinicalTrial.gov NCT01253928 PMID:25330088

  8. Partial inhibition of adipose tissue lipolysis improves glucose metabolism and insulin sensitivity without alteration of fat mass.

    Directory of Open Access Journals (Sweden)

    Amandine Girousse

    Full Text Available When energy is needed, white adipose tissue (WAT provides fatty acids (FAs for use in peripheral tissues via stimulation of fat cell lipolysis. FAs have been postulated to play a critical role in the development of obesity-induced insulin resistance, a major risk factor for diabetes and cardiovascular disease. However, whether and how chronic inhibition of fat mobilization from WAT modulates insulin sensitivity remains elusive. Hormone-sensitive lipase (HSL participates in the breakdown of WAT triacylglycerol into FAs. HSL haploinsufficiency and treatment with a HSL inhibitor resulted in improvement of insulin tolerance without impact on body weight, fat mass, and WAT inflammation in high-fat-diet-fed mice. In vivo palmitate turnover analysis revealed that blunted lipolytic capacity is associated with diminution in FA uptake and storage in peripheral tissues of obese HSL haploinsufficient mice. The reduction in FA turnover was accompanied by an improvement of glucose metabolism with a shift in respiratory quotient, increase of glucose uptake in WAT and skeletal muscle, and enhancement of de novo lipogenesis and insulin signalling in liver. In human adipocytes, HSL gene silencing led to improved insulin-stimulated glucose uptake, resulting in increased de novo lipogenesis and activation of cognate gene expression. In clinical studies, WAT lipolytic rate was positively and negatively correlated with indexes of insulin resistance and WAT de novo lipogenesis gene expression, respectively. In obese individuals, chronic inhibition of lipolysis resulted in induction of WAT de novo lipogenesis gene expression. Thus, reduction in WAT lipolysis reshapes FA fluxes without increase of fat mass and improves glucose metabolism through cell-autonomous induction of fat cell de novo lipogenesis, which contributes to improved insulin sensitivity.

  9. Partial inhibition of adipose tissue lipolysis improves glucose metabolism and insulin sensitivity without alteration of fat mass.

    Science.gov (United States)

    Girousse, Amandine; Tavernier, Geneviève; Valle, Carine; Moro, Cedric; Mejhert, Niklas; Dinel, Anne-Laure; Houssier, Marianne; Roussel, Balbine; Besse-Patin, Aurèle; Combes, Marion; Mir, Lucile; Monbrun, Laurent; Bézaire, Véronic; Prunet-Marcassus, Bénédicte; Waget, Aurélie; Vila, Isabelle; Caspar-Bauguil, Sylvie; Louche, Katie; Marques, Marie-Adeline; Mairal, Aline; Renoud, Marie-Laure; Galitzky, Jean; Holm, Cecilia; Mouisel, Etienne; Thalamas, Claire; Viguerie, Nathalie; Sulpice, Thierry; Burcelin, Rémy; Arner, Peter; Langin, Dominique

    2013-01-01

    When energy is needed, white adipose tissue (WAT) provides fatty acids (FAs) for use in peripheral tissues via stimulation of fat cell lipolysis. FAs have been postulated to play a critical role in the development of obesity-induced insulin resistance, a major risk factor for diabetes and cardiovascular disease. However, whether and how chronic inhibition of fat mobilization from WAT modulates insulin sensitivity remains elusive. Hormone-sensitive lipase (HSL) participates in the breakdown of WAT triacylglycerol into FAs. HSL haploinsufficiency and treatment with a HSL inhibitor resulted in improvement of insulin tolerance without impact on body weight, fat mass, and WAT inflammation in high-fat-diet-fed mice. In vivo palmitate turnover analysis revealed that blunted lipolytic capacity is associated with diminution in FA uptake and storage in peripheral tissues of obese HSL haploinsufficient mice. The reduction in FA turnover was accompanied by an improvement of glucose metabolism with a shift in respiratory quotient, increase of glucose uptake in WAT and skeletal muscle, and enhancement of de novo lipogenesis and insulin signalling in liver. In human adipocytes, HSL gene silencing led to improved insulin-stimulated glucose uptake, resulting in increased de novo lipogenesis and activation of cognate gene expression. In clinical studies, WAT lipolytic rate was positively and negatively correlated with indexes of insulin resistance and WAT de novo lipogenesis gene expression, respectively. In obese individuals, chronic inhibition of lipolysis resulted in induction of WAT de novo lipogenesis gene expression. Thus, reduction in WAT lipolysis reshapes FA fluxes without increase of fat mass and improves glucose metabolism through cell-autonomous induction of fat cell de novo lipogenesis, which contributes to improved insulin sensitivity. PMID:23431266

  10. Glucose turnover and hormonal changes during insulin-induced hypoglycemia in trained humans

    DEFF Research Database (Denmark)

    Kjær, Michael; Mikines, K J; Christensen, N J;

    1984-01-01

    Eight athletes (T), studied the third morning after the last exercise session, and seven sedentary males (C) (maximal O2 consumption 65 +/- 4 vs. 49 +/- 4 (SE) ml X kg-1 X min-1, for T and C men, respectively) had insulin infused until plasma glucose, at an insulin level of 1,600 pmol X l-1, was ...... of heart rate, free fatty acid, and glycerol was faster. Responses of norepinephrine, cortisol, C-peptide, and lactate were similar in the two groups. Training radically changes hormonal responses but not glucose kinetics in insulin hypoglycemia....

  11. A common polymorphism near the interleukin-6 gene modifies the association between dietary fat intake and insulin sensitivity

    Directory of Open Access Journals (Sweden)

    Cuda C

    2012-01-01

    Full Text Available Cristina Cuda1, Bibiana Garcia-Bailo1,2, Mohamed Karmali1,2, Ahmed El-Sohemy1, Alaa Badawi21Department of Nutritional Sciences, University of Toronto, 2Office of Biotechnology, Genomics and Population Health, Public Health Agency of Canada, Toronto, Ontario, CanadaBackground: Increasing evidence suggests a role for inflammation in the development of type 2 diabetes. Elevated levels of inflammatory cytokines, including interleukin-6, have been associated with insulin resistance, and dietary lipids can increase cytokine production. The objective of this study was to determine whether a single nucleotide polymorphism near the IL6 gene (rs7801406 modifies the relationship between dietary fat and markers of insulin sensitivity.Methods: Subjects were healthy men and women aged 20–29 years from the Toronto Nutrigenomics and Health Study. Dietary intake was estimated using a one-month semiquantitative food frequency questionnaire. Fasting blood samples were taken for genotyping and biomarker measurement.Results: The single nucleotide polymorphism was not associated with any of the measures of insulin sensitivity. However, it modified the relationship between total dietary fat and the homeostasis model assessment of insulin resistance (P = 0.053 for interaction. Total fat intake was positively related to HOMA-IR in individuals homozygous for the G allele (ß = 0.005 ± 0.002, P = 0.03, but not among heterozygotes. There was an inverse relationship between total fat intake and HOMA-IR in individuals who were homozygous for the A allele (β= –0.012 ± 0.006, P = 0.047.Conclusion: These findings suggest that dietary fat influences insulin sensitivity differently depending on genotype.Keywords: interleukin-6, insulin sensitivity, nutrigenomics, dietary fat

  12. mRNA expression of diacylglycerol kinase isoforms in insulin-sensitive tissues: effects of obesity and insulin resistance.

    Science.gov (United States)

    Mannerås-Holm, Louise; Kirchner, Henriette; Björnholm, Marie; Chibalin, Alexander V; Zierath, Juleen R

    2015-04-01

    Diacylglycerol kinase (DGK) isoforms regulate signal transduction and lipid metabolism. DGKδ deficiency leads to hyperglycemia, peripheral insulin resistance, and metabolic inflexibility. Thus, dysregulation of other DGK isoforms may play a role in metabolic dysfunction. We investigated DGK isoform mRNA expression in extensor digitorum longus (EDL) and soleus muscle, liver as well as subcutaneous and epididymal adipose tissue in C57BL/6J mice and obese and insulin-resistant ob/ob mice. All DGK isoforms, except for DGKκ, were detectable, although with varying mRNA expression. Liver DGK expression was generally lowest, with several isoforms undetectable. In soleus muscle, subcutaneous and epididymal adipose tissue, DGKδ was the most abundant isoform. In EDL muscle, DGKα and DGKζ were the most abundant isoforms. In liver, DGKζ was the most abundant isoform. Comparing obese insulin-resistant ob/ob mice to lean C57BL/6J mice, DGKβ, DGKι, and DGKθ were increased and DGKε expression was decreased in EDL muscle, while DGKβ, DGKη and DGKθ were decreased and DGKδ and DGKι were increased in soleus muscle. In liver, DGKδ and DGKζ expression was increased in ob/ob mice. DGKη was increased in subcutaneous fat, while DGKζ was increased and DGKβ, DGKδ, DGKη and DGKε were decreased in epididymal fat from ob/ob mice. In both adipose tissue depots, DGKα and DGKγ were decreased and DGKι was increased in ob/ob mice. In conclusion, DGK mRNA expression is altered in an isoform- and tissue-dependent manner in obese insulin-resistant ob/ob mice. DGK isoforms likely have divergent functional roles in distinct tissues, which may contribute to metabolic dysfunction. PMID:25847921

  13. Insulin resistance induced by physical inactivity is associated with multiple transcriptional changes in skeletal muscle in young men

    DEFF Research Database (Denmark)

    Alibegovic, A C; Sonne, M P; Højbjerre, L;

    2010-01-01

    Physical inactivity is a risk factor for insulin resistance. We examined the effect of 9 days of bed rest on basal and insulin-stimulated expression of genes potentially involved in insulin action by applying hypothesis-generating microarray in parallel with candidate gene real-time PCR approaches...... contribute to the development of insulin resistance induced by bed rest. Lack of complete normalization of changes after 4 wk of retraining underscores the importance of maintaining a minimum of daily physical activity....

  14. Adiponectin concentration is associated with muscle insulin sensitivity, AMPK phosphorylation and ceramide content in skeletal muslce of men, but not women

    DEFF Research Database (Denmark)

    Høeg, Louise Dalgas; Sjøberg, Kim Anker; Lundsgaard, Anne-Marie;

    2013-01-01

    Adiponectin is an adipokine that regulates metabolism and increases insulin sensitivity. Mechanisms behind this insulin sensitizing effect have been investigated in rodents, but little is known in humans especially in skeletal muscle. Women have higher serum concentrations of adiponectin than men...

  15. Endogenous interleukin-10 protects against hepatic steatosis but does not improve insulin sensitivity during high-fat feeding in mice

    NARCIS (Netherlands)

    den Boer, Marion A. M.; Voshol, Peter J.; Schroder-van der Elst, Janny P.; Korsheninnikova, Elena; Ouwens, D. Margriet; Kuipers, Folkert; Havekes, Louis M.; Romijn, Johannes A.

    2006-01-01

    Several studies have demonstrated an association in humans between plasma levels or production capacity of the antiinflammatory cytokine IL-10 and insulin sensitivity. The aim of our study was to investigate the protective role of endogenous IL-10 availability in the development of diet-induced insu

  16. The dipeptidyl peptidase-4 inhibitor vildagliptin improves beta-cell function and insulin sensitivity in subjects with impaired fasting glucose

    DEFF Research Database (Denmark)

    Utzschneider, Kristina M; Tong, Jenny; Montgomery, Brenda;

    2007-01-01

    OBJECTIVE: To evaluate the effect of treatment with the dipeptidyl peptidase (DPP)-4 inhibitor vildagliptin on insulin sensitivity and beta-cell function in subjects with impaired fasting glucose (IFG). RESEARCH DESIGN AND METHODS: A total of 22 subjects with IFG (11 female and 11 male, mean +/- ...

  17. Age-dependent nongenetic influences of birth weight and adult body fat on insulin sensitivity in twins

    DEFF Research Database (Denmark)

    Monrad, Rikke Nygaard; Grunnet, Louise Groth; Rasmussen, Eva Lind;

    2009-01-01

    We hypothesized a nongenetic influence of birth weight (BW) and twin and zygosity status on dual-energy x-ray absorptiometry determined adult total and regional body composition and a quantitative equal, although independent, importance of adult body composition and BW for insulin sensitivity....

  18. Effect of moderate alcohol consumption on adipokines and insulin sensitivity in lean and overweight men: A diet intervention study

    NARCIS (Netherlands)

    Beulens, J.W.J.; Zoete, E.C.de; Kok, F.J.; Schaafsma, G.; Hendriks, H.F.J.

    2008-01-01

    Objective: Moderate alcohol consumption is associated with a decreased risk of type II diabetes. This study investigates the effect of moderate alcohol consumption on adipokines and insulin sensitivity. Subjects: Twenty healthy, lean (body mass index (BMI) 18.5-25 kg/m2; n=11) or overweight (BMI>27

  19. Effects of a Growth Hormone-Releasing Hormone Analog on Endogenous GH Pulsatility and Insulin Sensitivity in Healthy Men

    OpenAIRE

    Stanley, Takara L.; Chen, Cindy Y.; Branch, Karen L.; Makimura, Hideo; GRINSPOON, Steven K.

    2010-01-01

    Context and Objective: Strategies to augment pulsatile GH may be beneficial in patients with excess visceral adiposity, in whom GH secretion is reduced. The objective of this study was to determine the effects of a novel GHRH (GHRH1–44) analog, tesamorelin, on endogenous GH pulsatility and insulin sensitivity in healthy men.

  20. Fasting serum levels of ferritin are associated with impaired pancreatic beta cell function and decreased insulin sensitivity

    DEFF Research Database (Denmark)

    Bonfils, Linéa; Ellervik, Christina; Friedrich, Nele;

    2015-01-01

    Aims/hypothesis: Elevated serum ferritin levels are associated with an increased risk of type 2 diabetes, but the nature of this association remains elusive. The aim of this study was to test the hypothesis that an elevated fasting serum ferritin level is associated with an increased risk of type 2...... of insulin sensitivity and HOMA-IR (p fasting serum...

  1. The effect of dietary phytosphingosine on cholesterol levels and insulin sensitivity in subjects with the metabolic syndrome

    NARCIS (Netherlands)

    Snel, M.; Sleddering, M.A.; Pijl, H.; Nieuwenhuizen, W.F.; Frölich, M.; Havekes, L.M.; Romijn, J.A.; Jazet, I.M.

    2010-01-01

    Background: Sphingolipids, like phytosphingosine (PS) are part of cellular membranes of yeasts, vegetables and fruits. Addition of PS to the diet decreases serum cholesterol and free fatty acid (FFA) levels in rodents and improves insulin sensitivity.Objective:To study the effect of dietary suppleme

  2. Thrombospondin1 deficiency reduces obesity-associated inflammation and improves insulin sensitivity in a diet-induced obese mouse model.

    Directory of Open Access Journals (Sweden)

    Yanzhang Li

    Full Text Available BACKGROUND: Obesity is prevalent worldwide and is associated with insulin resistance. Advanced studies suggest that obesity-associated low-grade chronic inflammation contributes to the development of insulin resistance and other metabolic complications. Thrombospondin 1 (TSP1 is a multifunctional extracellular matrix protein that is up-regulated in inflamed adipose tissue. A recent study suggests a positive correlation of TSP1 with obesity, adipose inflammation, and insulin resistance. However, the direct effect of TSP1 on obesity and insulin resistance is not known. Therefore, we investigated the role of TSP1 in mediating obesity-associated inflammation and insulin resistance by using TSP1 knockout mice. METHODOLOGY/PRINCIPAL FINDINGS: Male TSP1-/- mice and wild type littermate controls were fed a low-fat (LF or a high-fat (HF diet for 16 weeks. Throughout the study, body weight and fat mass increased similarly between the TSP1-/- mice and WT mice under HF feeding conditions, suggesting that TSP1 deficiency does not affect the development of obesity. However, obese TSP1-/- mice had improved glucose tolerance and increased insulin sensitivity compared to the obese wild type mice. Macrophage accumulation and inflammatory cytokine expression in adipose tissue were reduced in obese TSP1-/- mice. Consistent with the local decrease in pro-inflammatory cytokine levels, systemic inflammation was also decreased in the obese TSP1-/- mice. Furthermore, in vitro data demonstrated that TSP1 deficient macrophages had decreased mobility and a reduced inflammatory phenotype. CONCLUSION: TSP1 deficiency did not affect the development of high-fat diet induced obesity. However, TSP1 deficiency reduced macrophage accumulation in adipose tissue and protected against obesity related inflammation and insulin resistance. Our data demonstrate that TSP1 may play an important role in regulating macrophage function and mediating obesity-induced inflammation and insulin

  3. Adipose Tissue Promotes a Serum Cytokine Profile Related to Lower Insulin Sensitivity after Chronic Central Leptin Infusion

    Science.gov (United States)

    Burgos-Ramos, Emma; Canelles, Sandra; Perianes-Cachero, Arancha; Arilla-Ferreiro, Eduardo; Argente, Jesús; Barrios, Vicente

    2012-01-01

    Obesity is an inflammatory state characterized by an augment in circulating inflammatory factors. Leptin may modulate the synthesis of these factors by white adipose tissue decreasing insulin sensitivity. We have examined the effect of chronic central administration of leptin on circulating levels of cytokines and the possible relationship with cytokine expression and protein content as well as with leptin and insulin signaling in subcutaneous and visceral adipose tissues. In addition, we analyzed the possible correlation between circulating levels of cytokines and peripheral insulin resistance. We studied 18 male Wistar rats divided into controls (C), those treated icv for 14 days with a daily dose of 12 μg of leptin (L) and a pair-fed group (PF) that received the same food amount consumed by the leptin group. Serum leptin and insulin were measured by ELISA, mRNA levels of interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-4, IL-6, IL-10 and tumor necrosis factor-α (TNF-α) by real time PCR and serum and adipose tissue levels of these cytokines by multiplexed bead immunoassay. Serum leptin, IL-2, IL-4, IFN-γ and HOMA-IR were increased in L and TNF-α was decreased in PF and L. Serum leptin and IL-2 levels correlate positively with HOMA-IR index and negatively with serum glucose levels during an ip insulin tolerance test. In L, an increase in mRNA levels of IL-2 was found in both adipose depots and IFN-γ only in visceral tissue. Activation of leptin signaling was increased and insulin signaling decreased in subcutaneous fat of L. In conclusion, leptin mediates the production of inflammatory cytokines by adipose tissue independent of its effects on food intake, decreasing insulin sensitivity. PMID:23056516

  4. Pterocarpan-Enriched Soy Leaf Extract Ameliorates Insulin Sensitivity and Pancreatic β-Cell Proliferation in Type 2 Diabetic Mice

    Directory of Open Access Journals (Sweden)

    Un-Hee Kim

    2014-11-01

    Full Text Available In Korea, soy (Glycine max (L. Merr. leaves are eaten as a seasonal vegetable or pickled in soy sauce. Ethyl acetate extracts of soy leaves (EASL are enriched in pterocarpans and have potent α-glucosidase inhibitory activity. This study investigated the molecular mechanisms underlying the anti-diabetic effect of EASL in C57BL/6J mice with high-fat diet (HFD-induced type 2 diabetes. Mice were randomly divided into normal diet (ND, HFD (60 kcal% fat diet, EASL (HFD with 0.56% (wt/wt EASL, and Pinitol (HFD with 0.15% (wt/wt pinitol groups. Weight gain and abdominal fat accumulation were significantly suppressed by EASL. Levels of plasma glucose, HbA1c, and insulin in the EASL group were significantly lower than those of the HFD group, and the pancreatic islet of the EASL group had greater size than those of the HFD group. EASL group up-regulated neurogenin 3 (Ngn3, paired box 4 (Pax4, and v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA, which are markers of pancreatic cell development, as well as insulin receptor substrate 1 (IRS1, IRS2, and glucose transporter 4 (GLUT4, which are related to insulin sensitivity. Furthermore, EASL suppressed genes involved in hepatic gluconeogenesis and steatosis. These results suggest that EASL improves plasma glucose and insulin levels in mice with HDF-induced type 2 diabetes by regulating β-cell proliferation and insulin sensitivity.

  5. A novel function of B-cell translocation gene 1 (BTG1) in the regulation of hepatic insulin sensitivity in mice via c-Jun.

    Science.gov (United States)

    Xiao, Fei; Deng, Jiali; Yu, Junjie; Guo, Yajie; Chen, Shanghai; Guo, Feifan

    2016-01-01

    Insulin resistance is one of the major factors contributing to metabolic diseases, but the underlying mechanisms are still poorly understood. As an important cofactor, B-cell translocation gene 1 (BTG1) is involved in many physiologic processes; however, the direct effect of BTG1 on insulin sensitivity has not been described. In our study, BTG1 overexpression or knockdown improved or impaired insulin signaling in vitro, respectively. In addition, adenovirus-mediated BTG1 overexpression improved insulin sensitivity in wild-type (WT) and insulin-resistant leptin-receptor mutated (db/db) mice. In addition, transgenic BTG1-overexpressing mice were resistant to high-carbohydrate diet-induced insulin resistance. Adenovirus-mediated BTG1 knockdown consistently impaired insulin sensitivity in WT and insulin-sensitive leucine-deprived mice. Moreover, hepatic BTG1 expression was increased by leucine deprivation via the mammalian target of rapamycin/ribosomal protein S6 kinase 1 pathway. Furthermore, c-Jun expression was up-regulated by BTG1, and adenovirus-mediated c-Jun knockdown blocked BTG1-improved insulin signaling and insulin sensitivity in vitro and in vivo. Finally, BTG1 promoted c-Jun expression via stimulating c-Jun and retinoic acid receptor activities. Taken together, these results identify a novel function for BTG1 in the regulation of hepatic insulin sensitivity and provide important insights into the nutritional regulation of BTG1 expression.- Xiao, F., Deng, J., Yu, J., Guo, Y., Chen, S., Guo, F. A novel function of B-cell translocation gene 1 (BTG1) in the regulation of hepatic insulin sensitivity in mice via c-Jun.

  6. Enhanced insulin sensitivity mediated by adipose tissue browning perturbs islet morphology and hormone secretion in response to autonomic nervous activation in female mice.

    Science.gov (United States)

    Omar, Bilal A; Kvist-Reimer, Martina; Enerbäck, Sven; Ahrén, Bo

    2016-01-01

    Insulin resistance results in a compensatory increase in insulin secretion to maintain normoglycemia. Conversely, high insulin sensitivity results in reduced insulin secretion to prevent hypoglycemia. The mechanisms for this inverse adaptation are not well understood. We utilized highly insulin-sensitive mice, due to adipocyte-specific overexpression of the FOXC2 transcription factor, to study mechanisms of the reversed islet adaptation to increased insulin sensitivity. We found that Foxc2TG mice responded to mild hyperglycemia with insulin secretion significantly lower than that of wild-type mice; however, when severe hyperglycemia was induced, Foxc2TG mice demonstrated insulin secretion equal to or greater than that of wild-type mice. In response to autonomic nervous activation by 2-deoxyglucose, the acute suppression of insulin seen in wild-type mice was absent in Foxc2TG mice, suggesting impaired sympathetic signaling to the islet. Basal glucagon was increased in Foxc2TG mice, but they displayed severely impaired glucagon responses to cholinergic and autonomic nervous stimuli. These data suggest that the autonomic nerves contribute to the islet adaptation to high insulin sensitivity, which is compatible with a neuro-adipo regulation of islet function being instrumental for maintaining glucose regulation.

  7. Insulin-sensitizing and cardiovascular effects of the sodium-hydrogen exchange inhibitor, cariporide, in the JCR: LA-cp rat and db/db mouse.

    Science.gov (United States)

    Russell, J C; Proctor, S D; Kelly, S E; Löhn, M; Busch, A E; Schäfer, S

    2005-12-01

    The effects of the sodium-hydrogen (Na/H) exchange inhibitor cariporide (HOE642), on insulin sensitivity and vascular function were studied in the JCR:LA-cp rat and the db/db mouse. In the insulin-resistant rat, cariporide reduced fasting insulin levels (42%, P JCR:LA-cp insulin-resistant rat, which develops advanced cardiovascular disease and ischemic myocardial lesions. It also improved vascular function in a similar mouse model of insulin resistance. These effects were markedly greater than those of ramipril.

  8. Synergistic effects of leucine and resveratrol on insulin sensitivity and fat metabolism in adipocytes and mice

    Directory of Open Access Journals (Sweden)

    Bruckbauer Antje

    2012-08-01

    Full Text Available Abstract Background Sirtuins are important regulators of glucose and fat metabolism, and sirtuin activation has been proposed as a therapeutic target for insulin resistance and diabetes. We have shown leucine to increase mitochondrial biogenesis and fat oxidation via Sirt1 dependent pathways. Resveratrol is a widely recognized activator of Sirt; however, the biologically-effective high concentrations used in cell and animal studies are generally impractical or difficult to achieve in humans. Accordingly, we sought to determine whether leucine would exhibit synergy with low levels of resveratrol on sirtuin-dependent outcomes in adipocytes and in diet-induced obese (DIO mice. Methods 3T3-L1 mouse adipocytes were treated with Leucine (0.5 mM, β-hydroxy-β-methyl butyrate (HMB (5 μM or Resveratrol (200 nM alone or in combination. In addition, diet-induced obese mice were treated for 6-weeks with low (2 g/kg diet or high (10 g/kg diet dose HMB, Leucine (24 g/kg diet; 200% of normal level or low (12.5 mg/kg diet or high (225 mg/kg diet dose resveratrol, alone or as combination with leucine-resveratrol or HMB-resveratrol. Results Fatty acid oxidation, AMPK, Sirt1 and Sirt3 activity in 3T3-L1 adipocytes and in muscle cells, were significantly increased by the combinations compared to the individual treatments. Similarly, 6-week feeding of low-dose resveratrol combined with either leucine or its metabolite HMB to DIO mice increased adipose Sirt1 activity, muscle glucose and palmitate uptake (measured via PET/CT, insulin sensitivity (HOMAIR, improved inflammatory stress biomarkers (CRP, IL-6, MCP-1, adiponectin and reduced adiposity comparable to the effects of high dose resveratrol, while low-dose resveratrol exerted no independent effect. Conclusion These data demonstrate that either leucine or its metabolite HMB may be combined with a low concentration of resveratrol to exert synergistic effects on Sirt1-dependent outcomes; this may result in more

  9. Antidiabetic property of Symplocos cochinchinensis is mediated by inhibition of alpha glucosidase and enhanced insulin sensitivity.

    Directory of Open Access Journals (Sweden)

    Kalathookunnel Antony Antu

    Full Text Available The study is designed to find out the biochemical basis of antidiabetic property of Symplocos cochinchinensis (SC, the main ingredient of 'Nisakathakadi' an Ayurvedic decoction for diabetes. Since diabetes is a multifactorial disease, ethanolic extract of the bark (SCE and its fractions (hexane, dichloromethane, ethyl acetate and 90% ethanol were evaluated by in vitro methods against multiple targets relevant to diabetes such as the alpha glucosidase inhibition, glucose uptake, adipogenic potential, oxidative stress, pancreatic beta cell proliferation, inhibition of protein glycation, protein tyrosine phosphatase-1B (PTP-1B and dipeptidyl peptidase-IV (DPP-IV. Among the extracts, SCE exhibited comparatively better activity like alpha glucosidase inhibition (IC50 value-82.07 ± 2.10 µg/mL, insulin dependent glucose uptake (3 fold increase in L6 myotubes, pancreatic beta cell regeneration in RIN-m5F (3.5 fold increase and reduced triglyceride accumulation (22% decrease in 3T3L1 cells, protection from hyperglycemia induced generation of reactive oxygen species in HepG2 cells (59.57% decrease with moderate antiglycation and PTP-1B inhibition. Chemical characterization by HPLC revealed the superiority of SCE over other extracts due to presence and quantity of bioactives (beta-sitosterol, phloretin 2'glucoside, oleanolic acid in addition to minerals like magnesium, calcium, potassium, sodium, zinc and manganese. So SCE has been subjected to oral sucrose tolerance test to evaluate its antihyperglycemic property in mild diabetic and diabetic animal models. SCE showed significant antihyperglycemic activity in in vivo diabetic models. We conclude that SC mediates the antidiabetic activity mainly via alpha glucosidase inhibition, improved insulin sensitivity, with moderate antiglycation and antioxidant activity.

  10. Mediterranean diet and insulin sensitivity, lipid profile and blood pressure levels, in overweight and obese people; The Attica study

    Directory of Open Access Journals (Sweden)

    Zampelas Antonis

    2007-09-01

    Full Text Available Abstract Background We aimed to investigate if overweight and obese adults "close" to Mediterranean diet present better insulin, lipids profile and better pressure levels, compared to individuals close to a more Westernized diet. Methods The ATTICA study is a population-based cohort that has randomly enrolled 3042 adult men and women, stratified by age – gender, from the greater area of Athens, during 2001–2002. Of them, in this work were have studied 1762 participants with excess body weight, meaning overweight (BMI: 25–29.9 kg/m2 and obese (BMI>30 kg/m2. 1064 were men and 698 women (20–89 years old. Adherence to Mediterranean diet was assessed through a diet-score that was based on a validated food-frequency questionnaire. Blood pressure was measured and also fasting glucose, insulin and blood lipids. Insulin sensitivity was also assessed by the homeostasis model assessment (HOMA approach (glucose × insulin/22.5. Results Individuals with excess bodyweight in the highest tertile of diet score, were more insulin sensitive than those in the lowest tertile (11.4% lower HOMA, p = 0.06, had 13% lower levels of total cholesterol (p = 0.001 and 3 mmHg decrease of systolic blood pressure levels (p Conclusion Adherence to Mediterranean diet is modeslty associated with a better insulin sensitivity, lower levels of total cholesterol and lower levels of systolic blood pressure in overweight and obese subjects. This may suggest that compared to general population, the beneficial effect of this diet in cardiovascular system of excess body weight people is limited.

  11. The effect of rosuvastatin on insulin sensitivity and pancreatic beta-cell function in nondiabetic renal transplant recipients.

    Science.gov (United States)

    Sharif, A; Ravindran, V; Moore, R; Dunseath, G; Luzio, S; Owens, D; Baboolal, K

    2009-06-01

    Interventions to attenuate abnormal glycemia posttransplantation are required. In addition, surrogate markers of declining glycemic control are valuable. Statins may have pleiotropic properties that attenuate abnormal glucose metabolism. We hypothesized statins would improve glucose metabolism and HbA1c would be advantageous as a surrogate for worsening glycemia. We conducted a prospective, randomized, placebo controlled, crossover study in 20 nondiabetic renal transplant recipients at low risk for NODAT and compared effects of rosuvastatin on insulin secretion/sensitivity. Mathematical model analysis of an intravenous glucose tolerance test determined first-phase insulin secretion, insulin sensitivity and disposition index. Second-phase insulin secretion was determined with a meal tolerance test. Biochemical/clinical parameters were also assessed. Rosuvastatin significantly improved total cholesterol (-30%, p < 0.001), LDL cholesterol (-44%, p < 0.001) and triglycerides (-19%, p = 0.013). C-reactive protein decreased but failed to achieve statistical significance (-31%, p = 0.097). Rosuvastatin failed to influence any glycemic physiological parameter, although an inadequate timeframe to allow pleiotropic mechanisms to clinically manifest raises the possibility of a type II statistical error. On multivariate analysis, glycated hemoglobin (HbA1c) correlated with disposition index (R(2)= 0.201, p = 0.006), first-phase insulin secretion (R(2)= 0.106, p = 0.049) and insulin sensitivity (R(2)= 0.136, p = 0.029). Rosuvastatin fails to modify glucose metabolism in low-risk patients posttransplantation but HbA1c is a useful surrogate for declining glycemic control. PMID:19459810

  12. Limitations in the use of indices using glucose and insulin levels to predict insulin sensitivity: impact of race and gender and superiority of the indices derived from oral glucose tolerance test in African Americans.

    Science.gov (United States)

    Pisprasert, Veeradej; Ingram, Katherine H; Lopez-Davila, Maria F; Munoz, A Julian; Garvey, W Timothy

    2013-04-01

    OBJECTIVE To examine the utility of commonly used insulin sensitivity indices in nondiabetic European Americans (EAs) and African Americans (AAs). RESEARCH DESIGN AND METHODS Two-hundred forty nondiabetic participants were studied. Euglycemic-hyperinsulinemic clamp was the gold standard approach to assess glucose disposal rates (GDR) normalized by lean body mass. The homeostatic model assessment for insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI) were calculated from fasting plasma glucose and insulin (FIL). Oral glucose tolerance test (OGTT) was performed to determine Matsuda index, the simple index assessing insulin sensitivity (SI(is)OGTT), Avignon index, and Stomvoll index. Relationships among these indices with GDR were analyzed by multiple regression. RESULTS GDR values were similar in EA and AA subgroups; even so, AA exhibited higher FIL and were insulin-resistant compared with EA, as assessed by HOMA-IR, QUICKI, Matsuda index, SI(is)OGTT, Avignon index, and Stumvoll index. In the overall study population, GDR was significantly correlated with all studied insulin sensitivity indices (/r/ = 0.381-0.513); however, these indices were not superior to FIL in predicting GDR. Race and gender affected the strength of this relationship. In AA males, FIL and HOMA-IR were not correlated with GDR. In contrast, Matsuda index and SI(is)OGTT were significantly correlated with GDR in AA males, and Matsuda index was superior to HOMA-IR and QUICKI in AAs overall. CONCLUSIONS Insulin sensitivity indices based on glucose and insulin levels should be used cautiously as measures of peripheral insulin sensitivity when comparing mixed gender and mixed race populations. Matsuda index and SI(is)OGTT are reliable in studies that include AA males.

  13. Kazinol B from Broussonetia kazinoki improves insulin sensitivity via Akt and AMPK activation in 3T3-L1 adipocytes.

    Science.gov (United States)

    Lee, Hyejin; Li, Hua; Jeong, Ji Hye; Noh, Minsoo; Ryu, Jae-Ha

    2016-07-01

    In this study, we evaluated the insulin-sensitizing effect of flavans purified from Broussonetia kazinoki Siebold (BK) on 3T3-L1 adipocytes. Among the tested compounds, kazinol B enhanced intracellular lipid accumulation, gene expression of proliferator-activated receptorγ (PPARγ) and CCAAT/enhancer binding protein-alpha (C/EBPα), and consistently induced PPARγ transcriptional activation. To further investigate the insulin-sensitizing effect of kazinol B, we measured glucose analogue uptake by fully differentiated adipocytes and myotubes. Kazinol B increased 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose (2-NBDG) uptake by cells by upregulating the gene expression and translocation of glucose transporter 4 (GLUT-4) into the plasma membrane in adipocytes. Kazinol B stimulated the gene expression and secretion of adiponectin, which is associated with a low risk of types 1 and 2 diabetes mellitus. We also suggested the mechanism of the antidiabetic effect of kazinol B by assaying Akt and AMP-activated protein kinase (AMPK) phosphorylation. In conclusion, kazinol B isolated from BK improved insulin sensitivity by enhancing glucose uptake via the insulin-Akt signaling pathway and AMPK activation. These results suggest that kazinol B might be a therapeutic candidate for diabetes mellitus. PMID:27223849

  14. Overfeeding reduces insulin sensitivity and increases oxidative stress, without altering markers of mitochondrial content and function in humans.

    Directory of Open Access Journals (Sweden)

    Dorit Samocha-Bonet

    Full Text Available BACKGROUND: Mitochondrial dysfunction and increased oxidative stress are associated with obesity and type 2 diabetes. High fat feeding induces insulin resistance and increases skeletal muscle oxidative stress in rodents, but there is controversy as to whether skeletal muscle mitochondrial biogenesis and function is altered. METHODOLOGY AND PRINCIPAL FINDINGS: Forty (37 ± 2 y non-obese (25.6 ± 0.6 kg/m(2 sedentary men (n = 20 and women (n = 20 were overfed (+1040 ± 100 kcal/day, 46 ± 1% of energy from fat for 28 days. Hyperinsulinemic-euglycemic clamps were performed at baseline and day 28 of overfeeding and skeletal muscle biopsies taken at baseline, day 3 and day 28 of overfeeding in a sub cohort of 26 individuals (13 men and 13 women that consented to having all 3 biopsies performed. Weight increased on average in the whole cohort by 0.6 ± 0.1 and 2.7 ± 0.3 kg at days 3 and 28, respectively (P<0.0001, without a significant difference in the response between men and women (P = 0.4. Glucose infusion rate during the hyperinsulinemic-euglycemic clamp decreased from 54.8 ± 2.8 at baseline to 50.3 ± 2.5 µmol/min/kg FFM at day 28 of overfeeding (P = 0.03 without a significant difference between men and women (P = 0.4. Skeletal muscle protein carbonyls and urinary F2-isoprostanes increased with overfeeding (P<0.05. Protein levels of muscle peroxisome proliferator-activated receptor gamma coactivator-1α (PGC1α and subunits from complex I, II and V of the electron transport chain were increased at day 3 (all P<0.05 and returned to basal levels at day 28. No changes were detected in muscle citrate synthase activity or ex vivo CO(2 production at either time point. CONCLUSIONS: Peripheral insulin resistance was induced by overfeeding, without reducing any of the markers of mitochondrial content that were examined. Oxidative stress was however increased, and may have contributed to the reduction in insulin sensitivity observed.

  15. Insulin-like growth factor 2 silencing restores taxol sensitivity in drug resistant ovarian cancer.

    Science.gov (United States)

    Brouwer-Visser, Jurriaan; Lee, Jiyeon; McCullagh, KellyAnne; Cossio, Maria J; Wang, Yanhua; Huang, Gloria S

    2014-01-01

    Drug resistance is an obstacle to the effective treatment of ovarian cancer. We and others have shown that the insulin-like growth factor (IGF) signaling pathway is a novel potential target to overcome drug resistance. The purpose of this study was to validate IGF2 as a potential therapeutic target in drug resistant ovarian cancer and to determine the efficacy of targeting IGF2 in vivo. An analysis of The Cancer Genome Atlas (TCGA) data in the serous ovarian cancer cohort showed that high IGF2 mRNA expression is significantly associated with shortened interval to disease progression and death, clinical indicators of drug resistance. In a genetically diverse panel of ovarian cancer cell lines, the IGF2 mRNA levels measured in cell lines resistant to various microtubule-stabilizing agents including Taxol were found to be significantly elevated compared to the drug sensitive cell lines. The effect of IGF2 knockdown on Taxol resistance was investigated in vitro and in vivo. Transient IGF2 knockdown significantly sensitized drug resistant cells to Taxol treatment. A Taxol-resistant ovarian cancer xenograft model, developed from HEY-T30 cells, exhibited extreme drug resistance, wherein the maximal tolerated dose of Taxol did not delay tumor growth in mice. Blocking the IGF1R (a transmembrane receptor that transmits signals from IGF1 and IGF2) using a monoclonal antibody did not alter the response to Taxol. However, stable IGF2 knockdown using short-hairpin RNA in HEY-T30 effectively restored Taxol sensitivity. These findings validate IGF2 as a potential therapeutic target in drug resistant ovarian cancer and show that directly targeting IGF2 may be a preferable strategy compared with targeting IGF1R alone.

  16. Lactose in milk replacer can partly be replaced by glucose, fructose, or glycerol without affecting insulin sensitivity in veal calves.

    Science.gov (United States)

    Pantophlet, A J; Gilbert, M S; van den Borne, J J G C; Gerrits, W J J; Roelofsen, H; Priebe, M G; Vonk, R J

    2016-04-01

    Calf milk replacer (MR) contains 40 to 50% lactose. Lactose strongly fluctuates in price and alternatives are desired. Also, problems with glucose homeostasis and insulin sensitivity (i.e., high incidence of hyperglycemia and hyperinsulinemia) have been described for heavy veal calves (body weight >100kg). Replacement of lactose by other dietary substrates can be economically attractive, and may also positively (or negatively) affect the risk of developing problems with glucose metabolism. An experiment was designed to study the effects of replacing one third of the dietary lactose by glucose, fructose, or glycerol on glucose homeostasis and insulin sensitivity in veal calves. Forty male Holstein-Friesian (body weight=114±2.4kg; age=97±1.4 d) calves were fed an MR containing 462g of lactose/kg (CON), or an MR in which 150g of lactose/kg of MR was replaced by glucose (GLU), fructose (FRU), or glycerol (GLY). During the first 10d of the trial, all calves received CON. The CON group remained on this diet and the other groups received their experimental diets for a period of 8 wk. Measurements were conducted during the first (baseline) and last week of the trial. A frequently sampled intravenous glucose tolerance test was performed to assess insulin sensitivity and 24 h of urine was collected to measure glucose excretion. During the last week of the trial, a bolus of 1.5g of [U-(13)C] substrates was added to their respective meals and plasma glucose, insulin, and (13)C-glucose responses were measured. Insulin sensitivity was low at the start of the trial and remained low [1.2±0.1 and 1.0±0.1 (mU/L)(-1) × min(-1)], and no treatment effect was noted. Glucose excretion was low at the start of the trial (3.4±1.0g/d), but increased in CON and GLU calves (26.9±3.9 and 43.0±10.6g/d) but not in FRU and GLY calves. Postprandial glucose was higher in GLU, lower in FRU, and similar in GLY compared with CON calves. Postprandial insulin was lower in FRU and GLY and similar

  17. A highly sensitive peptide substrate for detecting two Aß-degrading enzymes: neprilysin and insulin-degrading enzyme.

    Science.gov (United States)

    Chen, Po-Ting; Liao, Tai-Yan; Hu, Chaur-Jong; Wu, Shu-Ting; Wang, Steven S-S; Chen, Rita P-Y

    2010-06-30

    Neprilysin has been singled out as the most promising candidate for use in the degradation of Abeta as a therapy for Alzheimer's disease. In this study, a quenched fluorogenic peptide substrate containing the first seven residues of the Abeta peptide plus a C-terminal Cysteine residue was synthesized to detect neprilysin activity. A fluorophore was attached to the C-terminal Cysteine and its fluorescence was quenched by a quencher linked to the N-terminus of the peptide. When this peptide substrate was degraded by an endopeptidase, fluorescence was produced and proved to be a sensitive detection system for endopeptidase activity. Our results showed that this assay system was extremely sensitive to neprilysin and insulin-degrading enzyme, but insensitive, or much less sensitive, to other Abeta-degrading enzymes. As low as 0.1 nM of neprilysin and 0.2 nM of insulin-degrading enzyme can be detected.

  18. The effect of TNFα on food intake and central insulin sensitivity in rats

    OpenAIRE

    de Kloet, Annette D.; Pacheco-López, Gustavo; Langhans, Wolfgang; Brown, Lynda M

    2010-01-01

    Circulating and tissue levels of the proinflammatory cytokine tumor necrosis factor α (TNFα) are elevated in obesity. TNFα interferes with insulin signaling in many tissues and also plays a causal role in the anorexia that accompanies severe challenges to the immune system. The interactions between TNFα and insulin in the control of eating are less well known. The present study evaluated the role of TNFα in the central nervous system control of food intake by insulin in adult male Long Evans ...

  19. Protein deficiency during pregnancy and lactation impairs glucose-induced insulin secretion but increases the sensitivity to insulin in weaned rats.

    Science.gov (United States)

    Latorraca, M Q; Carneiro, E M; Boschero, A C; Mello, M A

    1998-09-01

    We studied glucose homeostasis in rat pups from dams fed on a normal-protein (170 g/kg) (NP) diet or a diet containing 60 g protein/kg (LP) during fetal life and the suckling period. At birth, total serum protein, serum albumin and serum insulin levels were similar in both groups. However, body weight and serum glucose levels in LP rats were lower than those in NP rats. At the end of the suckling period (28 d of age), total serum protein, serum albumin and serum insulin were significantly lower and the liver glycogen and serum free fatty acid levels were significantly higher in LP rats compared with NP rats. Although the fasting serum glucose level was similar in both groups, the area under the blood glucose concentration curve after a glucose load was higher for NP rats (859 (SEM 58) mmol/l per 120 min for NP rats v. 607 (SEM 52) mmol/l per 120 min for LP rats; P < 0.005). The mean post-glucose increase in insulin was higher for NP rats (30 (SEM 4.7) nmol/l per 120 min for NP rats v. 17 (SEM 3.9) nmol/l per 120 min for LP rats; P < 0.05). The glucose disappearance rate for NP rats (0.7 (SEM 0.1) %/min) was lower than that for LP rats (1.6 (SEM 0.2) %/min; P < 0.001). Insulin secretion from isolated islets (1 h incubation) in response to 16.7 mmol glucose/l was augmented 14-fold in NP rats but only 2.6-fold in LP rats compared with the respective basal secretion (2.8 mmol/l; P < 0.001). These results indicate that in vivo as well as in vitro insulin secretion in pups from dams maintained on a LP diet is reduced. This defect may be counteracted by an increase in the sensitivity of target tissues to insulin. PMID:9875069

  20. Krüppel-like factor 14 increases insulin sensitivity through activation of PI3K/Akt signal pathway.

    Science.gov (United States)

    Yang, Min; Ren, Yan; Lin, Zhimin; Tang, Chenchen; Jia, Yanjun; Lai, Yerui; Zhou, Tingting; Wu, Shaobo; Liu, Hua; Yang, Gangyi; Li, Ling

    2015-11-01

    Genome-wide association studies (GWAS) have shown that Krüppel-like factor 14 (KLF14) is associated with type 2 diabetes mellitus (T2DM). However, no report has demonstrated a relationship between KLF14 and glucose metabolism. The aim of this study was to determine whether KLF14 is associated with glucose metabolism and insulin signaling in vitro. The mRNA and protein expressions of KLF14 were determined by Real-time PCR and Western blotting. Glucose uptake was assessed by 2-[(3)H]-deoxyglucose (2-DG) uptake. Western blotting was used to identify the activation of insulin signaling proteins. KLF14 mRNA and protein in fat and muscle were significantly decreased in HFD-fed mice, db/db mice and T2DM patients. Overexpression of KLF14 enhanced insulin-stimulated glucose uptake and the activation of Akt kinase in Hepa1-6 cells. The phosphorylation of insulin receptor (InsR), insulin receptor substrate-1(IRS-1), glycogen synthase kinase-3β (GSK-3β) and Akt also elevated significantly by up-regulation of KLF14. KLF14 overexpression in Hepa1-6 cells prevented the inhibition of glucose uptake and Akt phosphorylation induced by high glucose and/or high insulin, or T2DM serum. However, KLF14's ability to increase glucose uptake and Akt activation was significantly attenuated by LY294002, a PI3-kinase inhibitor. These data suggested that KLF14 could increase insulin sensitivity probably through the PI3K/Akt pathway. PMID:26226221

  1. Proinflammatory cytokine production and insulin sensitivity regulated by overexpression of resistin in 3T3-L1 adipocytes

    Directory of Open Access Journals (Sweden)

    Garvey W Timothy

    2006-07-01

    Full Text Available Abstract Resistin is secreted from adipocytes, and high circulating levels have been associated with obesity and insulin resistance. To investigate whether resistin could exert autocrine effects in adipocytes, we expressed resistin gene in 3T3-L1 fibroblasts using a lentiviral vector, and selected several stably-transduced cell lines under blasticidin selection. We observed that 3T3-L1 adipocytes expressing resistin have a decreased gene expression for related transcriptional factors (CCAAT/enhancer binding protein α(C/EBPα , peroxisome proliferator-activated receptor gamma (PPARγ, and adipocyte lipid binding protein (ALBP/aP2 which is one of target genes for the PPARγ during adipocyte differentiation,. Overexpression of resistin increased the levels of three proinflammatory cytokines, tumor necrosis factor alpha (TNFα, interleukin 6 (IL-6 and monocyte chemoattractant protein-1 (MCP-1, which play important roles for insulin resistance, glucose and lipid metabolisms during adipogenesis. Furthermore, overexpressing resistin in adipocytes inhibits glucose transport 4 (GLUT4 activity and its gene expression, reducing insulin's ability for glucose uptake by 30 %. In conclusion, resistin overexpression in stably transduced 3T3-L1 cells resulted in: 1 Attenuation of programmed gene expression responsible for adipogenesis; 2 Increase in expression of proinflammatory cytokines; 3 Decrease in insulin responsiveness of the glucose transport system. These data suggest a new role for resistin as an autocrine/paracrine factor affecting inflammation and insulin sensitivity in adipose tissue.

  2. Effects of telmisartan on metabolic changes and insulin sensitivity in elderly patients with type 2 diabetes mellitus and hypertension%替米沙坦对老年2型糖尿病合并高血压患者糖脂代谢及胰岛素敏感性的影响

    Institute of Scientific and Technical Information of China (English)

    于晓红; 于志宏

    2011-01-01

    目的 探讨血管紧张素受体拮抗药替米沙坦对老年2型糖尿病合并高血压患者糖脂代谢及胰岛素敏感性的作用.方法 48例老年2型糖尿病合并高血压患者按体重指数(body mass index,BMI)分为非肥胖组和肥胖组.每位患者每天空腹口服80 mg替米沙坦,共24周.测定治疗前后BMI、腰臀比(waist-to-hip ratio,WHR)、胰岛素、血糖、血脂、血压、肝功能、肾功能、血管紧张素Ⅱ,计算稳态模型胰岛素抵抗指数(HOMA-IR).结果 替米沙坦治疗前,与非肥胖组相比,肥胖组收缩压(SBP)、舒张压(DBP)、三酰甘油(triglyceride,TG)、胆固醇(total cholesterol,TC)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,LDL-C)、空腹血糖(fasting plasma glucose,FPG)、空腹胰岛素值(fasting insulin,FINS)、HOMA指数(homeostasis model assessment - insulin resistance index,HOMA-IR)和血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)均升高,差异有统计学意义(P<005).非肥胖组替米沙坦治疗后,SBP、FINS、HOMA-IR水平与治疗前相比均下降,ANGⅡ水平升高,差异有统计学意义.肥胖组替米沙坦治疗后,SBP、DBP、TG、TC、FPG、FINS、HOMA-IR水平与治疗前相比均下降,差异有统计学意义(P<005).结论 替米沙坦能够有效降低老年2型糖尿病合并高血压患者的血压,明显改善其糖、脂代谢状态,增强机体对胰岛素的敏感性.%Objective To evaluate the effect of teimisartan, an angiotensin Ⅱ ATI receptor blocker (ARB), on metabolism and insulin sensitivity in elderly patients with type 2.diabetes mellitus and hypertension.Methods Subjects were divided into two groups according to the body mass index (BMI): the group of nonobese patients (n =20) and the group of obese patients (n =28).All the patients were administered telmisartan 80mg/d for 24 weeks.BMI, waist hip ratio (WHR), systolic blood pressure ( SBP),diastolic blood pressure (DBP), triglyceride (TG), total cholesterol ( TC ), low

  3. Genetic factors modulate the impact of pubertal androgen excess on insulin sensitivity and fertility.

    Directory of Open Access Journals (Sweden)

    Abigail R Dowling

    Full Text Available Polycystic ovary syndrome (PCOS is the most common endocrine disorder of reproductive age women. The syndrome is caused by a combination of environmental influences and genetic predisposition. Despite extensive efforts, the heritable factors contributing to PCOS development are not fully understood. The objective of this study was to test the hypothesis that genetic background contributes to the development of a PCOS-like reproductive and metabolic phenotype in mice exposed to excess DHEA during the pubertal transition. We tested whether the PCOS phenotype would be more pronounced on the diabetes-prone C57BL/6 background than the previously used strain, BALB/cByJ. In addition, we examined strain-dependent upregulation of the expression of ovarian and extra-ovarian candidate genes implicated in human PCOS, genes containing known strain variants, and genes involved with steroidogenesis or insulin sensitivity. These studies show that there are significant strain-related differences in metabolic response to excess androgen exposure during puberty. Additionally, our results suggest the C57BL/6J strain provides a more robust and uniform experimental platform for PCOS research than the BALB/cByJ strain.

  4. Improved insulin sensitivity and islet function after PPARdelta activation in diabetic db/db mice.

    Science.gov (United States)

    Winzell, Maria Sörhede; Wulff, Erik Max; Olsen, Grith Skytte; Sauerberg, Per; Gotfredsen, Carsten F; Ahrén, Bo

    2010-01-25

    The peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the nuclear receptor superfamily. Several reports have shown that PPARdelta is involved in lipid metabolism, increasing fat oxidation and depleting lipid accumulation. Whether PPARdelta is involved in the regulation of glucose metabolism is not completely understood. In this study, we examined effects of long-term PPARdelta activation on glycemic control, islet function and insulin sensitivity in diabetic db/db mice. Male db/db mice were administered orally once daily with a selective and partial PPARdelta agonist (NNC 61-5920, 30 mg/kg) for eight weeks; control mice received vehicle. Fasting and non-fasting plasma glucose were reduced, reflected in reduced hemoglobinA(1c) (3.6+/-1.6% vs. 5.4+/-1.8 in db/db controls, Pdiabetic db/db mice. This suggests that activation of PPARdelta improves glucose metabolism and may therefore potentially be target for treatment of type 2 diabetes.

  5. 7-week aerobic exercise training reduces adipocyte area and improves insulin sensitivity in Wistar rats fed a highly palatable diet

    Directory of Open Access Journals (Sweden)

    Nádia F. Garcia

    2016-03-01

    Full Text Available Abstract The aim of this study was to evaluate the effect aerobic exercise training on fat pad mass, adipocyte size, leptin release and insulin sensitivity in rats fed with high fat-palatable diet. Twenty-four male Wistar rats (250-260g were divided into four groups: sedentary control (CTR/SD, trained control (CTR/TR, obese sedentary (OB/SD and obese trained (OB/TR. Obese groups were fed with high fat-palatable diet (27% of fat and control groups fed with AIN-93. Our results showed that aerobic exercise training was effective to reduce body weight and epididymal fat mass in CTR/TR and OB/TR. Insulin and glucose levels were increased in OB/TR compared with OB/SD. Aerobic exercise training reduced the average area of adipocytes in CTR/TR and OB/TR and it was associated with reduced plasma insulin and leptin. In conclusion, 7-week aerobic exercise training reduces adipocyte area and improves insulin sensitivity and leptin levels in high fat-palatable diet-fed Wistar rats.

  6. The possible role of mRNA expression changes of GH/IGF-1/insulin axis components in subcutaneous adipose tissue in metabolic disturbances of patients with acromegaly.

    Science.gov (United States)

    Touskova, V; Klouckova, J; Durovcova, V; Lacinova, Z; Kavalkova, P; Trachta, P; Kosak, M; Mraz, M; Haluzikova, D; Hana, V; Marek, J; Krsek, M; Haluzik, M

    2016-07-18

    We explored the effect of chronically elevated circulating levels of growth hormone (GH)/insulin-like-growth-factor-1 (IGF-1) on mRNA expression of GH/IGF-1/insulin axis components and p85alpha subunit of phosphoinositide-3-kinase (p85alpha) in subcutaneous adipose tissue (SCAT) of patients with active acromegaly and compared these findings with healthy control subjects in order to find its possible relationships with insulin resistance and body composition changes. Acromegaly group had significantly decreased percentage of truncal and whole body fat and increased homeostasis model assessment-insulin resistance (HOMA-IR). In SCAT, patients with acromegaly had significantly increased IGF-1 and IGF-binding protein-3 (IGFBP-3) expression that both positively correlated with serum GH. P85alpha expression in SCAT did not differ from control group. IGF-1 and IGFBP-3 expression in SCAT were not independently associated with percentage of truncal and whole body fat or with HOMA-IR while IGFBP-3 expression in SCAT was an independent predictor of insulin receptor as well as of p85alpha expression in SCAT. Our data suggest that GH overproduction in acromegaly group increases IGF-1 and IGFBP-3 expression in SCAT while it does not affect SCAT p85alpha expression. Increased IGF-1 or IGFBP-3 in SCAT of acromegaly group do not appear to contribute to systemic differences in insulin sensitivity but may have local regulatory effects in SCAT of patients with acromegaly.

  7. The possible role of mRNA expression changes of GH/IGF-1/insulin axis components in subcutaneous adipose tissue in metabolic disturbances of patients with acromegaly.

    Science.gov (United States)

    Touskova, V; Klouckova, J; Durovcova, V; Lacinova, Z; Kavalkova, P; Trachta, P; Kosak, M; Mraz, M; Haluzikova, D; Hana, V; Marek, J; Krsek, M; Haluzik, M

    2016-07-18

    We explored the effect of chronically elevated circulating levels of growth hormone (GH)/insulin-like-growth-factor-1 (IGF-1) on mRNA expression of GH/IGF-1/insulin axis components and p85alpha subunit of phosphoinositide-3-kinase (p85alpha) in subcutaneous adipose tissue (SCAT) of patients with active acromegaly and compared these findings with healthy control subjects in order to find its possible relationships with insulin resistance and body composition changes. Acromegaly group had significantly decreased percentage of truncal and whole body fat and increased homeostasis model assessment-insulin resistance (HOMA-IR). In SCAT, patients with acromegaly had significantly increased IGF-1 and IGF-binding protein-3 (IGFBP-3) expression that both positively correlated with serum GH. P85alpha expression in SCAT did not differ from control group. IGF-1 and IGFBP-3 expression in SCAT were not independently associated with percentage of truncal and whole body fat or with HOMA-IR while IGFBP-3 expression in SCAT was an independent predictor of insulin receptor as well as of p85alpha expression in SCAT. Our data suggest that GH overproduction in acromegaly group increases IGF-1 and IGFBP-3 expression in SCAT while it does not affect SCAT p85alpha expression. Increased IGF-1 or IGFBP-3 in SCAT of acromegaly group do not appear to contribute to systemic differences in insulin sensitivity but may have local regulatory effects in SCAT of patients with acromegaly. PMID:27070751

  8. Visual function and morphological changes in the macular area of patients with type 2 diabetes mellitus after intensive insulin therapy

    Institute of Scientific and Technical Information of China (English)

    Chen Zhenguo; Zhang Jiayu; Lu Chunjie; Lin Sisi; Chen Jiawei; Zhong Hongliang; Tian Bei

    2014-01-01

    Background Intensive insulin therapy has been found to lessen the progress of diabetic retinopathy (DR) to some extent,while it has also been implicated to be responsible for decrease of DR.We investigated visual function and morphological changes in the macular area in short-term follow-up of patients with type 2 diabetes mellitus after intensive insulin therapy.Methods This was a prospective clinical study of nonproliferative DR patients (102 eyes,120 patients) undergoing intensive insulin therapy.The Contrast Glare Tester (Takagi CGT-1000) was used to examine contrast sensitivity (CS) and Heidelberg Retina Tomograph (HRT) Ⅱ and Stratus Model 3000 OCT were used to observe the changes of morphology in the macular area.Follow-up times were pre-intensive therapy,3 and 6 months post-intensive therapy.Results CS at low and middle frequencies was higher at 3 and 6 months post-therapy compared with pre-therapy (P <0.05).Significant differences in CS at low frequency were found between 6 and 3 months post-therapy (P <0.05).Macular edema index was lower in the first,second,and third rings of the macular area after intensive therapy compared with pre-therapy (P <0.05).Compared with 3 months post-therapy,the macular edema index was lower in the first,second,and third rings of the macular area at 6 months post-therapy (P >0.05).No significant differences in the thickness of the first,second,and third rings of the macular area were detected between 3 and 6 months post-therapy and pre-therapy (P>0.05).Conclusion CS and macular edema indexes were significantly improved in nonproliferative diabetic retinopathy patients after intensive insulin therapy,but thickness of the macular area was unchanged.

  9. beta-Cell function and insulin sensitivity in adolescents from an OGTT

    Science.gov (United States)

    Given the increase in the incidence of insulin resistance, obesity, and type 2 diabetes in children and adolescents, it would be of paramount importance to assess quantitative indices of insulin secretion and action during a physiological perturbation, such as a meal or an oral glucose-tolerance tes...

  10. Muscle insulin sensitivity and glucose metabolism are controlled by the intrinsic muscle clock

    DEFF Research Database (Denmark)

    Dyar, Kenneth A.; Ciciliot, Stefano; Wright, Lauren E.;

    2014-01-01

    Circadian rhythms control metabolism and energy homeostasis, but the role of the skeletal muscle clock has never been explored. We generated conditional and inducible mouse lines with muscle-specific ablation of the core clock gene Bmal1. Skeletal muscles from these mice showed impaired insulin-s...

  11. The assembly of lipid droplets and its relation to cellular insulin sensitivity

    DEFF Research Database (Denmark)

    Boström, Pontus; Andersson, Linda; Li, Lu;

    2009-01-01

    and VAMP-4 (vesicle-associated protein 4). SNAP-23 is also involved in the insulin-dependent translocation of the glucose transporter GLUT4 to the plasma membrane. Fatty acids induce a missorting of SNAP-23, from the plasma membrane to the interior of the cell, resulting in cellular insulin resistance...

  12. Short-Term Estrogen Replacement Effects on Insulin Sensitivity and Glucose Tolerance in At-Risk Cats for Feline Diabetes Mellitus.

    Science.gov (United States)

    Wara, Allison; Hunsucker, Sara; Bove, Krystal; Backus, Robert

    2015-01-01

    Male domestic cats that are neutered and overweight are at an increased risk for developing a type-2-like diabetes mellitus. Beneficial effects of 17β-estradiol (E2) on glucose homeostasis may be lost with neutering and thereby account for increased diabetes risk. To evaluate this, adult male neutered overweight cats (n=6) were given daily E2 (1.0 μg/kg) or vehicle (Vh; ethanol, 1.0 μL/kg) in a single crossover trial of 14-day periods with a 7-day washout. The E2 and Vh were voluntarily ingested on food. The E2 dosage was determined in a pre-trial to significantly and transiently reduce food intake with no measurable change in plasma E2 concentration. During treatments, physical activity was assessed with collar-mounted accelerometers on days 9-11, and tests of intravenous insulin tolerance and intravenous glucose tolerance were conducted on days 13 and 14, respectively. Over the 14 days, E2 compared to Vh treatment reduced (p=0.03) food intake (- 22%) but not enough to significantly reduce body weight; activity counts were not significantly changed. With E2 compared to Vh treatment, the late-phase plasma insulin response of the glucose tolerance test was less (p=0.03) by 31%, while glucose tolerance and insulin sensitivity indexes were not significantly changed. The results indicate that oral E2 at a dosage that moderately affects food intake may reduce insulin requirement for achieving glucose homeostasis in neutered male cats. Further investigation is needed to identify the mechanism underlying the E2 effect.

  13. Short-Term Estrogen Replacement Effects on Insulin Sensitivity and Glucose Tolerance in At-Risk Cats for Feline Diabetes Mellitus.

    Directory of Open Access Journals (Sweden)

    Allison Wara

    Full Text Available Male domestic cats that are neutered and overweight are at an increased risk for developing a type-2-like diabetes mellitus. Beneficial effects of 17β-estradiol (E2 on glucose homeostasis may be lost with neutering and thereby account for increased diabetes risk. To evaluate this, adult male neutered overweight cats (n=6 were given daily E2 (1.0 μg/kg or vehicle (Vh; ethanol, 1.0 μL/kg in a single crossover trial of 14-day periods with a 7-day washout. The E2 and Vh were voluntarily ingested on food. The E2 dosage was determined in a pre-trial to significantly and transiently reduce food intake with no measurable change in plasma E2 concentration. During treatments, physical activity was assessed with collar-mounted accelerometers on days 9-11, and tests of intravenous insulin tolerance and intravenous glucose tolerance were conducted on days 13 and 14, respectively. Over the 14 days, E2 compared to Vh treatment reduced (p=0.03 food intake (- 22% but not enough to significantly reduce body weight; activity counts were not significantly changed. With E2 compared to Vh treatment, the late-phase plasma insulin response of the glucose tolerance test was less (p=0.03 by 31%, while glucose tolerance and insulin sensitivity indexes were not significantly changed. The results indicate that oral E2 at a dosage that moderately affects food intake may reduce insulin requirement for achieving glucose homeostasis in neutered male cats. Further investigation is needed to identify the mechanism underlying the E2 effect.

  14. Palmitoleic acid reduces intramuscular lipid and restores insulin sensitivity in obese sheep

    Directory of Open Access Journals (Sweden)

    Duckett SK

    2014-11-01

    downregulated (P<0.05 in ST muscle with C16:1 infusion. These results show that C16:1 infusion for 28 days reduced weight gain, intramuscular adipocyte size and total lipid content, and circulating insulin levels. These changes appear to be mediated through alterations in expression of genes regulating glucose uptake and fatty acid oxidation specifically in the muscles.Keywords: adipocytes, longissimus muscle, lipogenesis, insulin level, serum, fatty acid

  15. Testosterone replacement therapy improves insulin sensitivity and decreases high sensitivity C-reactive protein levels in hypogonadotropic hypogonadal young male patients

    Institute of Scientific and Technical Information of China (English)

    WU Xue-yan; MAO Jiang-feng; LU Shuang-yu; ZHANG Qian; SHI Yi-fan

    2009-01-01

    Background Many clinical studies suggest the inverse relationship between testosterone levels and insulin sensitivity in men, however the causative relationship of these two events is still not determined. The purpose of this study was to investigate the effects of testosterone replacement therapy (TRT) on insulin sensitivity, body composition, serum lipid profiles and high sensitivity C-reactive protein (hsCRP) in hypogonadotropic hypogonadal (HH) puberty undeveloped male patients.Methods In this prospectively designed study, we compared homeostasis model assessment of insulin resistance (HOMA-IR), insulin areas under the curves (AUC) of 3-hour oral glucose tolerance test (OGTT) and other metabolic parameters between 26 HH patients and 26 healthy men. The patients' HOMA-IR, insulin AUC, body composition, lipid profiles, hsCRP and other parameters were compared before and after nine-month TRT.Results The average levels of total testosterone (TT) in HH and healthy group were (0.9±0.6) nmol/L and (18.8±3.4) nmol/L, respectively. HOMA-IR in HH group was significantly higher than the healthy group (5.14±5.16 vs 2.00±1.38, P<0.005). Insulin AUC in 3-hour OGTT in HH group was significantly higher than the healthy group (698.6±414.7 vs 414.2±267.5, P<0.01). Fasting glucose level in HH group was significantly higher than control group ((5.1±0.6) mmol/L vs (4.7±0.3) mmol/l, P<0.005). Height, weight and grasp strength of the patients were significantly increased after 9-month TRT. Significant reductions in HOMA-IR (from 5.14±5.16 to 2.97±2.16, P<0.01), insulin AUC (from 698.6±414.7 to 511.7±253.9, P<0.01) and hsCRP (from (1.49±1.18) mg/L to (0.70±0.56) mg/L, P<0.05) were found after TRT. Serum total cholesterol, LDL-C, HDL-C and triglyceride were all decreased, albeit with no significant difference compared to the level prior to TRT.Conclusions HOMA-IR, insulin AUC and fasting glucose level in HH young male patients were significantly higher than

  16. Comparative Effect of Insulin Sensitizers and Statin on Metabolic Profile and Ultrasonographical Score in Non Alcoholic Fatty Liver Disease

    Science.gov (United States)

    Yadav, Suraj Singh; Reddy, Himanshu D.; Singhal, Shubham; Singh, Dinesh Kumar; Usman, Kauser

    2016-01-01

    Introduction Non Alcoholic Fatty Liver Disease (NAFLD) is a metabolic disorder involving fat accumulation in the liver. The initial management for patients with NAFLD includes lifestyle modification and weight loss in overweight or obese patients. Aim The present study was conducted to compare the efficacy of insulin sensitizers and statin in the patients of NAFLD. Materials and Methods The study included 98 patients diagnosed with NAFLD on USG (Ultrasonography) abdomen, divided into three Groups randomly and administered Metformin (Group I), Rosuvastatin (Group II) or Pioglitazone (Group III) along with dietary intervention and lifestyle modification. Their Body Mass Index (BMI), liver function tests, fasting lipid profile, USG scores for fatty liver were done and followed up at 4 weeks, 12 weeks and 24 week for change in above parameters. Results Out of the three Groups, Group II showed a maximum improvements in usg scores for NAFLD (p<0.001) and fasting lipid profile. Group II also showed maximum derangement of liver enzymes at 24 weeks though none of the subjects had more than three times elevation of liver enzymes. Conclusion Rosuvastatin may be an effective therapy as add on treatment to dietary and lifestyle intervention in patients of NAFLD. As an add-on treatment Rosuvastatin was superior to Pioglitazone or Metformin and acute decompensation is unlikely with this drug. Metformin was not effective as add on therapy for NAFLD, rather rapid weight loss in short period of time resulted in worsening of hepatic steatosis. PMID:27656480

  17. Heterodimerization of glycosylated insulin-like growth factor-1 receptors and insulin receptors in cancer cells sensitive to anti-IGF1R antibody.

    Directory of Open Access Journals (Sweden)

    Jun Gyu Kim

    Full Text Available Identification of predictive biomarkers is essential for the successful development of targeted therapy. Insulin-like growth factor 1 receptor (IGF1R has been examined as a potential therapeutic target for various cancers. However, recent clinical trials showed that anti-IGF1R antibody and chemotherapy are not effective for treating lung cancer.In order to define biomarkers for predicting successful IGF1R targeted therapy, we evaluated the anti-proliferation effect of figitumumab (CP-751,871, a humanized anti-IGF1R antibody, against nine gastric and eight hepatocellular cancer cell lines. Out of 17 cancer cell lines, figitumumab effectively inhibited the growth of three cell lines (SNU719, HepG2, and SNU368, decreased p-AKT and p-STAT3 levels, and induced G 1 arrest in a dose-dependent manner. Interestingly, these cells showed co-overexpression and altered mobility of the IGF1R and insulin receptor (IR. Immunoprecipitaion (IP assays and ELISA confirmed the presence of IGF1R/IR heterodimeric receptors in figitumumab-sensitive cells. Treatment with figitumumab led to the dissociation of IGF1-dependent heterodimeric receptors and inhibited tumor growth with decreased levels of heterodimeric receptors in a mouse xenograft model. We next found that both IGF1R and IR were N-linked glyosylated in figitumumab-sensitive cells. In particular, mass spectrometry showed that IGF1R had N-linked glycans at N913 in three figitumumab-sensitive cell lines. We observed that an absence of N-linked glycosylation at N913 led to a lack of membranous localization of IGF1R and figitumumab insensitivity.The data suggest that the level of N-linked glycosylated IGF1R/IR heterodimeric receptor is highly associated with sensitivity to anti-IGF1R antibody in cancer cells.

  18. Transcriptional Regulation by Nuclear Corepressors and PGC-1α: Implications for Mitochondrial Quality Control and Insulin Sensitivity

    Directory of Open Access Journals (Sweden)

    Zhengtang Qi

    2012-01-01

    Full Text Available The peroxisome proliferator-activated receptors (PPARs and estrogen-related receptor (ERRα are ligand-activated nuclear receptors that coordinately regulate gene expression. Recent evidence suggests that nuclear corepressors, NCoR, RIP140, and SMRT, repress nuclear receptors-mediated transcriptional activity on specific promoters, and thus regulate insulin sensitivity, adipogenesis, mitochondrial number, and activity in vivo. Moreover, the coactivator PGC-1α that increases mitochondrial biogenesis during exercise and calorie restriction directly regulates autophagy in skeletal muscle and mitophagy in the pathogenesis of Parkinson's disease. In this paper, we discuss the PGC-1α’s novel role in mitochondrial quality control and the role of nuclear corepressors in regulating insulin sensitivity and interacting with PGC-1α.

  19. Insulin sensitivity is independent of lipid binding protein trafficking at the plasma membrane in human skeletal muscle

    DEFF Research Database (Denmark)

    Jordy, Andreas Børsting; Serup, Annette Karen; Karstoft, Kristian;

    2014-01-01

    The aim of the present study was to investigate lipid-induced regulation of lipid binding proteins in human skeletal muscle and the impact hereof on insulin sensitivity. Eleven healthy male subjects underwent a 3-day hyper-caloric and high-fat diet regime. Muscle biopsies were taken before......-regulated by increased fatty acid availability. This suggests a time dependency in the up-regulation of FAT/CD36 and FABPpm protein during high availability of plasma fatty acids. Furthermore, we did not detect FATP1 and FATP4 protein in giant sarcolemmal vesicles obtained from human skeletal muscle. In conclusion......, this study shows that a short-term lipid-load increases mRNA content of key lipid handling proteins in human muscle. However, decreased insulin sensitivity after high-fat diet is not accompanied with relocation of FAT/CD36 or FABPpm protein to the sarcolemma. Finally, FATP1 and FATP4 protein could...

  20. Impact of objectively measured sedentary behaviour on changes in insulin resistance and secretion over 3 years in the RISC study

    DEFF Research Database (Denmark)

    Lahjibi, E; Heude, B; Dekker, J M;

    2013-01-01

    The importance of reducing sedentary time is increasingly being recognized in the prevention of diabetes and cardiovascular disease. Despite this, the prospective association between sedentary time and physical activity with insulin sensitivity and cardiometabolic risk factors has been little stu...

  1. Effects of Chronic Consumption of Sugar-Enriched Diets on Brain Metabolism and Insulin Sensitivity in Adult Yucatan Minipigs

    Science.gov (United States)

    Ochoa, Melissa; Malbert, Charles-Henri; Meurice, Paul; Val-Laillet, David

    2016-01-01

    Excessive sugar intake might increase the risk to develop eating disorders via an altered reward circuitry, but it remains unknown whether different sugar sources induce different neural effects and whether these effects are dependent from body weight. Therefore, we compared the effects of three high-fat and isocaloric diets varying only in their carbohydrate sources on brain activity of reward-related regions, and assessed whether brain activity is dependent on insulin sensitivity. Twenty-four minipigs underwent 18FDG PET brain imaging following 7-month intake of high-fat diets of which 20% in dry matter weight (36.3% of metabolisable energy) was provided by starch, glucose or fructose (n = 8 per diet). Animals were then subjected to a euglycemic hyperinsulinemic clamp to determine peripheral insulin sensitivity. After a 7-month diet treatment, all groups had substantial increases in body weight (from 36.02±0.85 to 63.33±0.81 kg; Pstarch, chronic exposure to fructose and glucose induced bilateral brain activations, i.e. increased basal cerebral glucose metabolism, in several reward-related brain regions including the anterior and dorsolateral prefrontal cortex, the orbitofrontal cortex, the anterior cingulate cortex, the caudate and putamen. The lack of differences in insulin sensitivity index and body weight suggests that the observed differences in basal brain glucose metabolism are not related to differences in peripheral insulin sensitivity and weight gain. The differences in basal brain metabolism in reward-related brain areas suggest the onset of cerebral functional alterations induced by chronic consumption of dietary sugars. Further studies should explore the underlying mechanisms, such as the availability of intestinal and brain sugar transporter, or the appearance of addictive-like behavioral correlates of these brain functional characteristics. PMID:27583555

  2. Effects of protein intake on blood pressure, insulin sensitivity and blood lipids in children: a systematic review.

    Science.gov (United States)

    Voortman, Trudy; Vitezova, Anna; Bramer, Wichor M; Ars, Charlotte L; Bautista, Paula K; Buitrago-Lopez, Adriana; Felix, Janine F; Leermakers, Elisabeth T M; Sajjad, Ayesha; Sedaghat, Sanaz; Tharner, Anne; Franco, Oscar H; van den Hooven, Edith H

    2015-02-14

    High protein intake in early childhood is associated with obesity, suggesting possible adverse effects on other cardiometabolic outcomes. However, studies in adults have suggested beneficial effects of protein intake on blood pressure (BP) and lipid profile. Whether dietary protein intake is associated with cardiovascular and metabolic health in children is unclear. Therefore, we aimed to systematically review the evidence on the associations of protein intake with BP, insulin sensitivity and blood lipids in children. We searched the databases Medline, Embase, Cochrane Central and PubMed for interventional and observational studies in healthy children up to the age of 18 years, in which associations of total, animal and/or vegetable protein intake with one or more of the following outcomes were reported: BP; measures of insulin sensitivity; cholesterol levels; or TAG levels. In the search, we identified 6636 abstracts, of which fifty-six studies met all selection criteria. In general, the quality of the included studies was low. Most studies were cross-sectional, and many did not control for potential confounders. No overall associations were observed between protein intake and insulin sensitivity or blood lipids. A few studies suggested an inverse association between dietary protein intake and BP, but evidence was inconclusive. Only four studies examined the effects of vegetable or animal protein intake, but with inconsistent results. In conclusion, the literature, to date provides insufficient evidence for effects of protein intake on BP, insulin sensitivity or blood lipids in children. Future studies could be improved by adequately adjusting for key confounders such as energy intake and obesity.

  3. Fructose Consumption: Considerations for Future Research on Its Effects on Adipose Distribution, Lipid Metabolism, and Insulin Sensitivity in Humans12

    OpenAIRE

    Stanhope, Kimber L.; Havel, Peter J.

    2009-01-01

    Results from a recent study investigating the metabolic effects of consuming fructose-sweetened beverages at 25% of energy requirements for 10 wk demonstrate that a high-fructose diet induces dyslipidemia, decreases insulin sensitivity, and increases visceral adiposity. The purpose of this review is to present aspects of the study design which may be critical for assessment of the metabolic effects of sugar consumption. Collection of postprandial blood samples is required to document the full...

  4. Effects of Chronic Consumption of Sugar-Enriched Diets on Brain Metabolism and Insulin Sensitivity in Adult Yucatan Minipigs.

    Science.gov (United States)

    Ochoa, Melissa; Malbert, Charles-Henri; Meurice, Paul; Val-Laillet, David

    2016-01-01

    Excessive sugar intake might increase the risk to develop eating disorders via an altered reward circuitry, but it remains unknown whether different sugar sources induce different neural effects and whether these effects are dependent from body weight. Therefore, we compared the effects of three high-fat and isocaloric diets varying only in their carbohydrate sources on brain activity of reward-related regions, and assessed whether brain activity is dependent on insulin sensitivity. Twenty-four minipigs underwent 18FDG PET brain imaging following 7-month intake of high-fat diets of which 20% in dry matter weight (36.3% of metabolisable energy) was provided by starch, glucose or fructose (n = 8 per diet). Animals were then subjected to a euglycemic hyperinsulinemic clamp to determine peripheral insulin sensitivity. After a 7-month diet treatment, all groups had substantial increases in body weight (from 36.02±0.85 to 63.33±0.81 kg; Pbrain activations, i.e. increased basal cerebral glucose metabolism, in several reward-related brain regions including the anterior and dorsolateral prefrontal cortex, the orbitofrontal cortex, the anterior cingulate cortex, the caudate and putamen. The lack of differences in insulin sensitivity index and body weight suggests that the observed differences in basal brain glucose metabolism are not related to differences in peripheral insulin sensitivity and weight gain. The differences in basal brain metabolism in reward-related brain areas suggest the onset of cerebral functional alterations induced by chronic consumption of dietary sugars. Further studies should explore the underlying mechanisms, such as the availability of intestinal and brain sugar transporter, or the appearance of addictive-like behavioral correlates of these brain functional characteristics. PMID:27583555

  5. mTOR Inhibition: Reduced Insulin Secretion and Sensitivity in a Rat Model of Metabolic Syndrome

    Science.gov (United States)

    Rovira, Jordi; Ramírez-Bajo, María Jose; Banon-Maneus, Elisenda; Moya-Rull, Daniel; Ventura-Aguiar, Pedro; Hierro-Garcia, Natalia; Lazo-Rodriguez, Marta; Revuelta, Ignacio; Torres, Armando; Oppenheimer, Federico; Campistol, Josep M.; Diekmann, Fritz

    2016-01-01

    Background Sirolimus (SRL) has been associated with new-onset diabetes mellitus after transplantation. The aim was to determine the effect of SRL on development of insulin resistance and β-cell toxicity. Methods Lean Zucker rat (LZR) and obese Zucker rat (OZR) were distributed into groups: vehicle and SRL (0.25, 0.5, or 1.0 mg/kg) during 12 or 28 days. Intraperitoneal glucose tolerance test (IPGTT) was evaluated at days 0, 12, 28, and 45. Islet morphometry, β-cell proliferation, and apoptosis were analyzed at 12 days. Islets were isolated to analyze insulin content, insulin secretion, and gene expression. Results After 12 days, SRL treatment only impaired IPGTT in a dose-dependent manner in OZR. Treatment prolongation induced increase of area under the curve of IPGTT in LZR and OZR; however, in contrast to OZR, LZR normalized glucose levels after 2 hours. The SRL reduced pancreas weight and islet proliferation in LZR and OZR as well as insulin content. Insulin secretion was only affected in OZR. Islets from OZR + SRL rats presented a downregulation of Neurod1, Pax4, and Ins2 gene. Genes related with insulin secretion remained unchanged or upregulated. Conclusions In conditions that require adaptive β-cell proliferation, SRL might reveal harmful effects by blocking β-cell proliferation, insulin production and secretion. These effects disappeared when removing the therapy. PMID:27500257

  6. Dissociated insulinotropic sensitivity to glucose and carbachol in high-fat diet-induced insulin resistance in C57BL/6J mice

    NARCIS (Netherlands)

    Ahren, B; Simonsson, E; Scheurink, AJW; Mulder, H; Myrsen, U; Sundler, F

    1997-01-01

    To study islet function following reduced insulin sensitivity, we examined mice of the C57BL/6J strain, the genotype of which carries an increased propensity to develop insulin resistance when metabolically challenged. The mice received either a high-fat diet (58% fat on an energy basis) or a contro

  7. An insulin based model to explain changes and interactions in human breath-holding.

    Science.gov (United States)

    Dangmann, Rosita

    2015-06-01

    Until now oxygen was thought to be the leading factor of hypoxic conditions. Whereas now it appears that insulin is the key regulator of hypoxic conditions. Insulin seems to regulate the redox state of the organism and to determine the breakpoint of human breath-holding. This new hypoxia-insulin hypotheses might have major clinical relevance. Besides the clinical relevance, this hypothesis could explain, for the first time, why the training of the diaphragm, among other factors, results in an increase in breath-holding performance. Elite freedivers/apnea divers are able to reach static breath-holding times to over 6 min. Untrained persons exhibit an unpleasant feeling after more or less a minute. Breath-holding is stopped at the breakpoint. The partial oxygen pressure as well as the carbon dioxide pressure failed to directly influence the breakpoint in earlier studies. The factors that contribute to the breakpoint are still under debate. Under hypoxic conditions the organism needs more glucose, because it changes from the oxygen consuming pentose phosphate (36 ATP/glucose molecule) to the anaerobic glycolytic pathway (2ATP/glucose molecule). Hence insulin, as it promotes the absorption of glucose, is set in the center of interest regarding hypoxic conditions. This paper provides an insulin based model that could explain the changes and interactions in human breath-holding. The correlation between hypoxia and reactive oxygen species (ROS) and their influence on the sympathetic nerve system and hypoxia-inducible factor 1 alpha (HIF-1α) is dealt with. It reviews as well the direct interrelation of HIF-1α and insulin. The depression of insulin secretion through the vagus nerve activation via inspiration is discussed. Furthermore the paper describes the action of insulin on the carotid bodies and the diaphragm and therefore a possible role in respiration pattern. Freedivers that go over the breakpoint of breath-holding could exhibit seizures and thus the effect of

  8. Identification of a mitochondrial target of thiazolidinedione insulin sensitizers (mTOT--relationship to newly identified mitochondrial pyruvate carrier proteins.

    Directory of Open Access Journals (Sweden)

    Jerry R Colca

    Full Text Available Thiazolidinedione (TZD insulin sensitizers have the potential to effectively treat a number of human diseases, however the currently available agents have dose-limiting side effects that are mediated via activation of the transcription factor PPARγ. We have recently shown PPARγ-independent actions of TZD insulin sensitizers, but the molecular target of these molecules remained to be identified. Here we use a photo-catalyzable drug analog probe and mass spectrometry-based proteomics to identify a previously uncharacterized mitochondrial complex that specifically recognizes TZDs. These studies identify two well-conserved proteins previously known as brain protein 44 (BRP44 and BRP44 Like (BRP44L, which recently have been renamed Mpc2 and Mpc1 to signify their function as a mitochondrial pyruvate carrier complex. Knockdown of Mpc1 or Mpc2 in Drosophila melanogaster or pre-incubation with UK5099, an inhibitor of pyruvate transport, blocks the crosslinking of mitochondrial membranes by the TZD probe. Knockdown of these proteins in Drosophila also led to increased hemolymph glucose and blocked drug action. In isolated brown adipose tissue (BAT cells, MSDC-0602, a PPARγ-sparing TZD, altered the incorporation of (13C-labeled carbon from glucose into acetyl CoA. These results identify Mpc1 and Mpc2 as components of the mitochondrial target of TZDs (mTOT and suggest that understanding the modulation of this complex, which appears to regulate pyruvate entry into the mitochondria, may provide a viable target for insulin sensitizing pharmacology.

  9. The exenatide analogue AC3174 attenuates hypertension, insulin resistance, and renal dysfunction in Dahl salt-sensitive rats

    Directory of Open Access Journals (Sweden)

    Fernandez Rayne

    2010-08-01

    Full Text Available Abstract Background Activation of glucagon-like peptide-1 (GLP-1 receptors improves insulin sensitivity and induces vasodilatation and diuresis. AC3174 is a peptide analogue with pharmacologic properties similar to the GLP-1 receptor agonist, exenatide. Hypothetically, chronic AC3174 treatment could attenuate salt-induced hypertension, cardiac morbidity, insulin resistance, and renal dysfunction in Dahl salt-sensitive (DSS rats. Methods DSS rats were fed low salt (LS, 0.3% NaCl or high salt (HS, 8% NaCl diets. HS rats were treated with vehicle, AC3174 (1.7 pmol/kg/min, or GLP-1 (25 pmol/kg/min for 4 weeks via subcutaneous infusion. Other HS rats received captopril (150 mg/kg/day or AC3174 plus captopril. Results HS rat survival was improved by all treatments except GLP-1. Systolic blood pressure (SBP was lower in LS rats and in GLP-1, AC3174, captopril, or AC3174 plus captopril HS rats than in vehicle HS rats (p Conclusions Thus, AC3174 had antihypertensive, cardioprotective, insulin-sensitizing, and renoprotective effects in the DSS hypertensive rat model. Furthermore, AC3174 improved animal survival, an effect not observed with GLP-1.

  10. Associations of Adiponectin with Adiposity, Insulin Sensitivity, and Diet in Young, Healthy, Mexican Americans and Non-Latino White Adults

    Directory of Open Access Journals (Sweden)

    Rocio I. Pereira

    2015-12-01

    Full Text Available Low circulating adiponectin levels may contribute to higher diabetes risk among Mexican Americans (MA compared to non-Latino whites (NLW. Our objective was to determine if among young healthy adult MAs have lower adiponectin than NLWs, independent of differences in adiposity. In addition, we explored associations between adiponectin and diet. This was an observational, cross-sectional study of healthy MA and NLW adults living in Colorado (U.S.A.. We measured plasma total adiponectin, adiposity (BMI, and visceral adipose tissue, insulin sensitivity (IVGTT, and self-reported dietary intake in 43 MA and NLW adults. Mean adiponectin levels were 40% lower among MA than NLW (5.8 ± 3.3 vs. 10.7 ± 4.2 µg/mL, p = 0.0003, and this difference persisted after controlling for age, sex, BMI, and visceral adiposity. Lower adiponectin in MA was associated with lower insulin sensitivity (R2 = 0.42, p < 0.01. Lower adiponectin was also associated with higher dietary glycemic index, lower intake of vegetables, higher intake of trans fat, and higher intake of grains. Our findings confirm that ethnic differences in adiponectin reflect differences in insulin sensitivity, but suggest that these are not due to differences in adiposity. Observed associations between adiponectin and diet support the need for future studies exploring the regulation of adiponectin by diet and other environmental factors.

  11. Effect of high-fat diets on body composition, lipid metabolism and insulin sensitivity, and the role of exercise on these parameters

    Directory of Open Access Journals (Sweden)

    D.F. Coelho

    2011-10-01

    Full Text Available Dietary fat composition can interfere in the development of obesity due to the specific roles of some fatty acids that have different metabolic activities, which can alter both fat oxidation and deposition rates, resulting in changes in body weight and/or composition. High-fat diets in general are associated with hyperphagia, but the type of dietary fat seems to be more important since saturated fats are linked to a positive fat balance and omental adipose tissue accumulation when compared to other types of fat, while polyunsaturated fats, omega-3 and omega-6, seem to increase energy expenditure and decrease energy intake by specific mechanisms involving hormone-sensitive lipase, activation of peroxisome proliferator-activated receptor α (PPARα and others. Saturated fat intake can also impair insulin sensitivity compared to omega-3 fat, which has the opposite effect due to alterations in cell membranes. Obesity is also associated with impaired mitochondrial function. Fat excess favors the production of malonyl-CoA, which reduces GLUT4 efficiency. The tricarboxylic acid cycle and beta-oxidation are temporarily uncoupled, forming metabolite byproducts that augment reactive oxygen species production. Exercise can restore mitochondrial function and insulin sensitivity, which may be crucial for a better prognosis in treating or preventing obesity.

  12. Transfer of Intestinal Microbiota From Lean Donors Increases Insulin Sensitivity in Individuals With Metabolic Syndrome

    NARCIS (Netherlands)

    Vrieze, A.; Nood, van E.; Holleman, F.; Heilig, G.H.J.; Zoetendal, E.G.; Vos, de W.M.

    2012-01-01

    Alterations in intestinal microbiota are associated with obesity and insulin resistance. We studied the effects of infusing intestinal microbiota from lean donors to male recipients with metabolic syndrome on the recipients' microbiota composition and glucose metabolism. Subjects were assigned rando

  13. NAMPT-Mediated NAD(+) Biosynthesis in Adipocytes Regulates Adipose Tissue Function and Multi-organ Insulin Sensitivity in Mice.

    Science.gov (United States)

    Stromsdorfer, Kelly L; Yamaguchi, Shintaro; Yoon, Myeong Jin; Moseley, Anna C; Franczyk, Michael P; Kelly, Shannon C; Qi, Nathan; Imai, Shin-Ichiro; Yoshino, Jun

    2016-08-16

    Obesity is associated with adipose tissue dysfunction and multi-organ insulin resistance. However, the mechanisms of such obesity-associated systemic metabolic complications are not clear. Here, we characterized mice with adipocyte-specific deletion of nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting NAD(+) biosynthetic enzyme known to decrease in adipose tissue of obese and aged rodents and people. We found that adipocyte-specific Nampt knockout mice had severe insulin resistance in adipose tissue, liver, and skeletal muscle and adipose tissue dysfunction, manifested by increased plasma free fatty acid concentrations and decreased plasma concentrations of a major insulin-sensitizing adipokine, adiponectin. Loss of Nampt increased phosphorylation of CDK5 and PPARγ (serine-273) and decreased gene expression of obesity-linked phosphorylated PPARγ targets in adipose tissue. These deleterious alterations were normalized by administering rosiglitazone or a key NAD(+) intermediate, nicotinamide mononucleotide (NMN). Collectively, our results provide important mechanistic and therapeutic insights into obesity-associated systemic metabolic derangements, particularly multi-organ insulin resistance. PMID:27498863

  14. NAMPT-mediated NAD+ biosynthesis in adipocytes regulates adipose tissue function and multi-organ insulin sensitivity in mice

    Science.gov (United States)

    Stromsdorfer, Kelly L.; Yamaguchi, Shintaro; Yoon, Myeong Jin; Moseley, Anna C.; Franczyk, Michael P.; Kelly, Shannon C.; Qi, Nathan; Imai, Shin-ichiro; Yoshino, Jun

    2016-01-01

    SUMMARY Obesity is associated with adipose tissue dysfunction and multi-organ insulin resistance. However, the mechanisms of such obesity-associated systemic metabolic complications are not clear. Here, we characterized mice with adipocyte-specific deletion of nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting NAD+ biosynthetic enzyme known to decrease in adipose tissue of obese and aged rodents and people. We found that adipocyte-specific Nampt knockout mice had severe insulin resistance in adipose tissue, liver, and skeletal muscle, and adipose tissue dysfunction, manifested by increased plasma free fatty acids concentrations and decreased plasma concentrations of a major insulin-sensitizing adipokine, adiponectin. Loss of Nampt increased phosphorylation of CDK5 and PPARγ (serine-273) and decreased gene expression of obesity-linked phosphorylated PPARγ targets in adipose tissue. Remarkably, these deleterious alterations were normalized by administering rosiglitazone or a key NAD+ intermediate, nicotinamide mononucleotide (NMN). Collectively, our results provide important mechanistic and therapeutic insights into obesity-associated systemic metabolic derangements, particularly multi-organ insulin resistance. PMID:27498863

  15. Hormone-sensitive lipase deficiency suppresses insulin secretion from pancreatic islets of Lep{sup ob/ob} mice

    Energy Technology Data Exchange (ETDEWEB)

    Sekiya, Motohiro [Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655 (Japan); Yahagi, Naoya, E-mail: nyahagi-tky@umin.ac.jp [Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655 (Japan); Laboratory of Molecular Physiology on Energy Metabolism, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655 (Japan); Tamura, Yoshiaki; Okazaki, Hiroaki; Igarashi, Masaki; Ohta, Keisuke; Takanashi, Mikio; Kumagai, Masayoshi; Takase, Satoru; Nishi, Makiko; Takeuchi, Yoshinori; Izumida, Yoshihiko; Kubota, Midori; Ohashi, Ken; Iizuka, Yoko [Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655 (Japan); Yagyu, Hiroaki [Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical University, Tochigi 329-0498 (Japan); Gotoda, Takanari [Department of Nephrology and Endocrinology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655 (Japan); Nagai, Ryozo [Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655 (Japan); Shimano, Hitoshi; Yamada, Nobuhiro [Advanced Biomedical Applications, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaragi 305-8575 (Japan); and others

    2009-09-25

    It has long been a matter of debate whether the hormone-sensitive lipase (HSL)-mediated lipolysis in pancreatic {beta}-cells can affect insulin secretion through the alteration of lipotoxicity. We generated mice lacking both leptin and HSL (Lep{sup ob/ob}/HSL{sup -/-}) and explored the role of HSL in pancreatic {beta}-cells in the setting of obesity. Lep{sup ob/ob}/HSL{sup -/-} developed elevated blood glucose levels and reduced plasma insulin levels compared with Lep{sup ob/ob}/HSL{sup +/+} in a fed state, while the deficiency of HSL did not affect glucose homeostasis in Lep{sup +/+} background. The deficiency of HSL exacerbated the accumulation of triglycerides in Lep{sup ob/ob} islets, leading to reduced glucose-stimulated insulin secretion. The deficiency of HSL also diminished the islet mass in Lep{sup ob/ob} mice due to decreased cell proliferation. In conclusion, HSL affects insulin secretary capacity especially in the setting of obesity.

  16. Researching Effective Strategies to Improve Insulin Sensitivity in Children and Teenagers - RESIST. A randomised control trial investigating the effects of two different diets on insulin sensitivity in young people with insulin resistance and/or pre-diabetes.

    OpenAIRE

    Sukanya; Parker Robert; Broderick Carolyn R; Chisholm Kerryn; Burrell Susie; Woodhead Helen J; Steinbeck Katharine; Noakes Manny; Baur Louise A; Garnett Sarah P; Shrinivasan Shubha; Hopley Lori; Hendrie Gilly; Ambler Geoffrey R; Kohn Michael R

    2010-01-01

    Abstract Background Concomitant with the rise in childhood obesity there has been a significant increase in the number of adolescents with clinical features of insulin resistance and prediabetes. Clinical insulin resistance and prediabetes are likely to progress to type 2 diabetes and early atherosclerosis if not targeted for early intervention. There are no efficacy trials of lifestyle intervention in this group to inform clinical practice. The primary aim of this randomised control trial (R...

  17. Mesoporous materials modified by aptamers and hydrophobic groups assist ultra-sensitive insulin detection in serum.

    Science.gov (United States)

    Lei, Chang; Xu, Chun; Noonan, Owen; Meka, Anand Kumar; Zhang, Long; Nouwens, Amanda; Yu, Chengzhong

    2015-09-14

    A novel mesoporous material modified with both insulin-binding-aptamers and hydrophobic methyl groups is synthesized. With rationally designed pore structures and surface chemistry, this material is applied in sample pre-treatment for ELISA, and enables the quantification (0.25-5 pg ml(-1)) of insulin in serum, 30-fold enhancement of the limit-of-detection compared to the commercial ELISA kit.

  18. INSR gene variation is associated with decreased insulin sensitivity in Iraqi women with PCOs

    OpenAIRE

    Manal T. Mutib; Farqad B. Hamdan; Anam R. Al-Salihi

    2014-01-01

    Background: Polycystic ovarian syndrome (PCOS) is a complex, heterogeneous disorder of uncertain etiology with strong genetic background. Insulin resistance is present in the majority of PCOS cases with linkage and association between single nucleotide polymorphisms of insulin receptor (INSR) gene and PCOS. Objective: To examine whether the exon 17 of INSR gene contributes to genetic susceptibility to PCOS in Iraqi women and its effects on glucose tolerance test and lipid profile. Mater...

  19. Muscle insulin sensitivity and glucose metabolism are controlled by the intrinsic muscle clock

    OpenAIRE

    Kenneth A. Dyar; Ciciliot, Stefano; Wright, Lauren E.; Biensø, Rasmus Sjørup; Tagliazucchi, Guidantonio M.; Patel, Vishal R.; Forcato, Mattia; Paz, Marcia I.P.; Gudiksen, Anders; Solagna, Francesca; Albiero, Mattia; Moretti, Irene; Eckel-Mahan, Kristin L.; Baldi, Pierre; Sassone-Corsi, Paolo

    2014-01-01

    Circadian rhythms control metabolism and energy homeostasis, but the role of the skeletal muscle clock has never been explored. We generated conditional and inducible mouse lines with muscle-specific ablation of the core clock gene Bmal1. Skeletal muscles from these mice showed impaired insulin-stimulated glucose uptake with reduced protein levels of GLUT4, the insulin-dependent glucose transporter, and TBC1D1, a Rab-GTPase involved in GLUT4 translocation. Pyruvate dehydrogenase (PDH) activit...

  20. Growth-Blocking Peptides As Nutrition-Sensitive Signals for Insulin Secretion and Body Size Regulation.

    Science.gov (United States)

    Koyama, Takashi; Mirth, Christen K

    2016-02-01

    In Drosophila, the fat body, functionally equivalent to the mammalian liver and adipocytes, plays a central role in regulating systemic growth in response to nutrition. The fat body senses intracellular amino acids through Target of Rapamycin (TOR) signaling, and produces an unidentified humoral factor(s) to regulate insulin-like peptide (ILP) synthesis and/or secretion in the insulin-producing cells. Here, we find that two peptides, Growth-Blocking Peptide (GBP1) and CG11395 (GBP2), are produced in the fat body in response to amino acids and TOR signaling. Reducing the expression of GBP1 and GBP2 (GBPs) specifically in the fat body results in smaller body size due to reduced growth rate. In addition, we found that GBPs stimulate ILP secretion from the insulin-producing cells, either directly or indirectly, thereby increasing insulin and insulin-like growth factor signaling activity throughout the body. Our findings fill an important gap in our understanding of how the fat body transmits nutritional information to the insulin producing cells to control body size. PMID:26928023

  1. Fitness, adiposopathy, and adiposity are independent predictors of insulin sensitivity in middle-aged men without diabetes.

    Science.gov (United States)

    Huth, Claire; Pigeon, Étienne; Riou, Marie-Ève; St-Onge, Josée; Arguin, Hélène; Couillard, Erick; Dubois, Marie-Julie; Marette, André; Tremblay, Angelo; Weisnagel, S John; Lacaille, Michel; Mauriège, Pascale; Joanisse, Denis R

    2016-09-01

    Adiposopathy, or sick fat, refers to adipose tissue dysfunction that can lead to several complications such as dyslipidemia, insulin resistance, and hyperglycemia. The relative contribution of adiposopathy in predicting insulin resistance remains unclear. We investigated the relationship between adiposopathy, as assessed as a low plasma adiponectin/leptin ratio, with anthropometry, body composition (hydrostatic weighing), insulin sensitivity (hyperinsulinemic-euglycemic clamp), inflammation, and fitness level (ergocycle VO2max, mL/kgFFM/min) in 53 men (aged 34-53 years) from four groups: sedentary controls without obesity (body mass index [BMI]  30 kg/m(2)), sedentary with obesity and glucose intolerance, and endurance trained active without obesity. The adiponectin/leptin ratio was the highest in trained men (4.75 ± 0.82) and the lowest in glucose intolerant subjects with obesity (0.27 ± 0.06; ANOVA p < 0.0001) indicating increased adiposopathy in those with obesity. The ratio was negatively associated with adiposity (e.g., waist circumference, r = -0.59, p < 0.01) and positively associated with VO2max (r = 0.67, p < 0.01) and insulin sensitivity (M/I, r = 0.73, p < 0.01). Multiple regression analysis revealed fitness as the strongest independent predictor of insulin sensitivity (partial R (2) = 0.61). While adiposopathy was also an independent and significant contributor (partial R (2) = 0.10), waist circumference added little power to the model (partial R (2) = 0.024). All three variables remained significant independent predictors when trained subjects were excluded from the model. Plasma lipids were not retained in the model. We conclude that low fitness, adiposopathy, as well as adiposity (and in particular abdominal obesity) are independent contributors to insulin resistance in men without diabetes. PMID:27139423

  2. The Attainment of High Sensitivity and Precision in Radioimmunoassay Techniques as Exemplified in a Simple Assay of Serum Insulin

    International Nuclear Information System (INIS)

    Recent controversy has underlined the fundamental confusion surrounding the concepts of assay ''sensitivity'' and ''precision'' and, in particular, their optimization in radioimmunoassay and other saturation assay procedures. Many formal definitions of sensitivity (e.g. that laid down by the American Chemical Society) express this concept in terms of the slope of the ''dose'' response curve; nevertheless, in common usage, the term is normally regarded as a synonym for the detection limit of the measurement technique. However, a technique which is ''sensitive'' in the formal sense may not display a low limit of detection, and it is readily demonstrable that, in radioimmunoassay systems in particular, there are circumstances in which increase in the slope of the response curve may lead to an increase in the detection limit of the assay. The authors have based their insulin assay protocols on mathematical principles specifically designed to lead to the minimization of the detection limit. The method depends on the use of (uncoated) charcoal for the separation of free and bound labelled insulin in incubation mixtures in which insulin-free human serum is used as diluent. The detection limit of the method is approximately 1 pg/ml of incubation mixture, corresponding to roughly 0.25 μU/ml of serum at the serum dilutions used. In a formal comparative study, the method has been shown to be more sensitive, precise and accurate than other methods relying on double antibody or chromato-electrophoietic separation. The relevance of such factors as high specific activity labelled hormone to the attainment of high sensitivity is discussed. (author)

  3. Fatty-acid binding protein 4 gene variants and childhood obesity: potential implications for insulin sensitivity and CRP levels

    Directory of Open Access Journals (Sweden)

    Bhattacharjee Rakesh

    2010-02-01

    Full Text Available Abstract Introduction Obesity increases the risk for insulin resistance and metabolic syndrome in both adults and children. FABP4 is a member of the intracellular lipid-binding protein family that is predominantly expressed in adipose tissue, and plays an important role in maintaining glucose and lipid homeostasis. The purpose of this study was to measure FABP4 plasma levels, assess FABP4 allelic variants, and explore potential associations with fasting glucose and insulin levels in young school-age children with and without obesity. Methods A total of 309 consecutive children ages 5-7 years were recruited. Children were divided based on BMI z score into Obese (OB; BMI z score >1.65 and non-obese (NOB. Fasting plasma glucose, lipids, insulin, hsCRP, and FABP4 levels were measured. HOMA was used as correlate of insulin sensitivity. Four SNPs of the human FABP4 gene (rs1051231, rs2303519, rs16909233 and rs1054135, corresponding to several critical regions of the encoding FABP4 gene sequence were genotyped. Results Compared to NOB, circulating FABP4 levels were increased in OB, as were LDL, hsCRP and HOMA. FABP4 levels correlated with BMI, and also contributed to the variance of HOMA and hsCRP, but not serum lipids. The frequency of rs1054135 allelic variant was increased in OB, and was associated with increased FABP4 levels, while the presence of rs16909233 variant allele, although similar in OB and NOB, was associated with increased HOMA values. Conclusions Childhood obesity is associated with higher FABP4 levels that may promote cardiometabolic risk. The presence of selective SNPs in the FABP4 gene may account for increased risk for insulin resistance or systemic inflammation in the context of obesity.

  4. Changes in platelet function, blood coagulation and fibrinolysis during insulin-induced hypoglycaemia in juvenile diabetics and normal subjects

    DEFF Research Database (Denmark)

    Dalsgaard-Nielsen, J; Madsbad, S; Hilsted, J

    1982-01-01

    in the diabetics after hypoglycaemia, whereas no changes were seen in the control group. The activated partial thromboplastin time (APTT) was reduced in both groups and significantly lower in the diabetics than in the controls 120 min after insulin infusion. Fibrinogen and factor VIII R:Ag increased after insulin...... infusion; highest values were seen in the diabetics. The euglobulin clot lysis time (ELT) was reduced in both groups during insulin infusion; 120 min after end of insulin infusion ELT was significantly longer in the diabetics than in the control group.......Haemostatic parameters were assessed before insulin induced hypoglycaemia and 0, 1 and 2 hr after discontinuation of insulin infusion in 7 non-diabetics, aged 28 (22-31) years (mean and range), and 8 juvenile diabetics, aged 31 (27-35) years, with a mean duration of diabetes of 4 years...

  5. Elevation in Tanis expression alters glucose metabolism and insulin sensitivity in H4IIE cells.

    Science.gov (United States)

    Gao, Yuan; Walder, Ken; Sunderland, Terry; Kantham, Lakshmi; Feng, Helen C; Quick, Melissa; Bishara, Natalie; de Silva, Andrea; Augert, Guy; Tenne-Brown, Janette; Collier, Gregory R

    2003-04-01

    Increased hepatic glucose output and decreased glucose utilization are implicated in the development of type 2 diabetes. We previously reported that the expression of a novel gene, Tanis, was upregulated in the liver during fasting in the obese/diabetic animal model Psammomys obesus. Here, we have further studied the protein and its function. Cell fractionation indicated that Tanis was localized in the plasma membrane and microsomes but not in the nucleus, mitochondria, or soluble protein fraction. Consistent with previous gene expression data, hepatic Tanis protein levels increased more significantly in diabetic P. obesus than in nondiabetic controls after fasting. We used a recombinant adenovirus to increase Tanis expression in hepatoma H4IIE cells and investigated its role in metabolism. Tanis overexpression reduced glucose uptake, basal and insulin-stimulated glycogen synthesis, and glycogen content and attenuated the suppression of PEPCK gene expression by insulin, but it did not affect insulin-stimulated insulin receptor phosphorylation or triglyceride synthesis. These results suggest that Tanis may be involved in the regulation of glucose metabolism, and increased expression of Tanis could contribute to insulin resistance in the liver.

  6. 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

  7. Haemodynamic changes in insulin-induced hypoglycaemia in normal man

    DEFF Research Database (Denmark)

    Hilsted, J; Bonde-Petersen, F; Nørgaard, M B;

    1984-01-01

    ). The early rise in cardiac output was primarily due to an increase in heart rate, but later mainly due to increased stroke volume. Since pulmonary tissue volume was constant, the observed changes in cardiac output are unlikely to be due to a Frank-Starling mechanism but rather to increased sympatho...

  8. Coordinated balancing of muscle oxidative metabolism through PGC-1α increases metabolic flexibility and preserves insulin sensitivity

    International Nuclear Information System (INIS)

    Highlights: → PGC-1α enhances muscle oxidative capacity. → PGC-1α promotes concomitantly positive and negative regulators of lipid oxidation. → Regulator abundance enhances metabolic flexibility and balances oxidative metabolism. → Balanced oxidation prevents detrimental acylcarnitine and ROS generation. → Absence of detrimental metabolites preserves insulin sensitivity -- Abstract: The peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) enhances oxidative metabolism in skeletal muscle. Excessive lipid oxidation and electron transport chain activity can, however, lead to the accumulation of harmful metabolites and impair glucose homeostasis. Here, we investigated the effect of over-expression of PGC-1α on metabolic control and generation of insulin desensitizing agents in extensor digitorum longus (EDL), a muscle that exhibits low levels of PGC-1α in the untrained state and minimally relies on oxidative metabolism. We demonstrate that PGC-1α induces a strictly balanced substrate oxidation in EDL by concomitantly promoting the transcription of activators and inhibitors of lipid oxidation. Moreover, we show that PGC-1α enhances the potential to uncouple oxidative phosphorylation. Thereby, PGC-1α boosts elevated, yet tightly regulated oxidative metabolism devoid of side products that are detrimental for glucose homeostasis. Accordingly, PI3K activity, an early phase marker for insulin resistance, is preserved in EDL muscle. Our findings suggest that PGC-1α coordinately coactivates the simultaneous transcription of gene clusters implicated in the positive and negative regulation of oxidative metabolism and thereby increases metabolic flexibility. Thus, in mice fed a normal chow diet, over-expression of PGC-1α does not alter insulin sensitivity and the metabolic adaptations elicited by PGC-1α mimic the beneficial effects of endurance training on muscle metabolism in this context.

  9. Circulating insulin stimulates fatty acid retention in white adipose tissue via KATP channel activation in the central nervous System only in insulin-sensitive mice

    NARCIS (Netherlands)

    Coomans, C.P.; Geerling, J.J.; Guigas, B.; Hoek, A.M. van den; Parlevliet, E.T.; Ouwens, D.M.; Pijl, H.; Voshol, P.J.; Rensen, P.C.N.; Havekes, L.M.; Romijn, J.A.

    2011-01-01

    Insulin signaling in the central nervous system (CNS) is required for the inhibitory effect of insulin on glucose production. Our aim was to determine whether the CNS is also involved in the stimulatory effect of circulating insulin on the tissue-specific retention of fatty acid (FA) from plasma. In

  10. Moderate alcohol consumption is associated with improved insulin sensitivity, reduced basal insulin secretion rate and lower fasting glucagon concentration in healthy women

    DEFF Research Database (Denmark)

    Bonnet, F; Disse, E; Laville, M;

    2012-01-01

    Moderate alcohol consumption is associated with a reduced risk of type 2 diabetes with a stronger effect in women. As the underlying mechanisms remain poorly characterised, we investigated its relationship with insulin resistance, insulin secretion, clearance of insulin and glucagon concentration....

  11. Intramyocellular lipid content and insulin sensitivity are increased following a short-term low-glycemic index diet and exercise intervention

    DEFF Research Database (Denmark)

    Haus, Jacob M; Solomon, Thomas; Lu, Lan;

    2011-01-01

    The relationship between intramyocellular (IMCL) and extramyocellular lipid (EMCL) accumulation and skeletal muscle insulin resistance is complex and dynamic. We examined the effect of a short-term (7-day) low-glycemic index (LGI) diet and aerobic exercise training intervention (EX) on IMCL...... = 0.03). The LGI/EX group also demonstrated greater reductions in [EMCL] than the HGI/EX group (Δ: -5.8 ± 3.4, LGI/EX; 2.3 ± 1.1, HGI/EX, P = 0.03). Changes in muscle lipids and insulin sensitivity were not correlated; however, the change in [IMCL]/[EMCL] was negatively associated with the change...... in FPI (r = -0.78, P = 0.002) and HOMA-IR (r = -0.61, P = 0.03). These data suggest that increases in the IMCL pool following a low glycemic diet and exercise intervention may represent lipid repartitioning from EMCL. The lower systemic glucose levels that prevail while eating a low glycemic diet may...

  12. Atorvastatin improves insulin sensitivity in mice with obesity induced by monosodium glutamate

    OpenAIRE

    Zhang, Ning; Huan, Yi; Huang, Hui; Song, Guang-ming; Sun, Su-juan; Shen, Zhu-fang

    2009-01-01

    Aim: To examine the mechanisms underlying the effects of atorvastatin on glucose and lipid metabolism. Methods: Mice with insulin resistance and obesity induced by monosodium glutamate (MSG) were used. Atorvastatin (80 mg·kg−1·d−1) or vehicle control treatment was given orally once a day for 30 days. Plasma levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and free fatty acids were monitored. Serum insulin an...

  13. Increased insulin sensitivity and responsiveness of glucose metabolism in adipocytes from female versus male rats.

    OpenAIRE

    Guerre-Millo, M.; Leturque, A.; Girard, J.; Lavau, M

    1985-01-01

    This study was undertaken to examine whether there were sex-associated differences in the action of insulin on glucose metabolism in adipocytes. Insulin binding and the dose-response curves for glucose transport (assessed by measuring the cell-associated radioactivity after 15-s incubation with 50 microM [6-14C]glucose) and [U-14C]glucose (5 mM) metabolism into CO2 and lipids were compared in retroperitoneal adipocytes from age-matched (84 d) male and female rats. In addition, the activity of...

  14. Effects of chromium supplementation to feedlot steers on growth performance, insulin sensitivity, and carcass characteristics.

    Science.gov (United States)

    Kneeskern, S G; Dilger, A C; Loerch, S C; Shike, D W; Felix, T L

    2016-01-01

    Objectives were to determine the effects of chromium propionate supplementation on growth performance, insulin and glucose metabolism, and carcass characteristics of beef cattle. Steers ( = 34) were stratified by BW and assigned to 1 of 2 treatments: 1) no supplemental Cr (Cont) or 2) 3 mg supplemental Cr·steer·d (CrP). Both supplements, Cont and CrP, were delivered via 0.454 kg ground corn top-dressed on the basal diet. There was no effect ( ≥ 0.45) of CrP on ADG, DMI, G:F, or final BW. However, steers fed CrP needed more ( = 0.10) days on feed (DOF) to achieve the same carcass back fat (BF) as steers fed Cont. There were no effects ( ≥ 0.41) of CrP on HCW, BF, or KPH. Steers fed CrP had increased ( = 0.01) dressing percentage (DP) and tended to have a 4.21 cm greater LM area ( = 0.15), decreased marbling scores ( = 0.11), and decreased intramuscular fat ( = 0.11) compared to steers fed Cont. There were no differences ( ≥ 0.25) in quality or yield grade distributions. A glucose tolerance test was conducted early (21 DOF) and late (98 DOF) in the finishing phase. There was a feedlot treatment (FT) × time × DOF interaction ( = 0.08) for glucose concentrations, but no other interactions ( ≥ 0.21) for glucose or insulin concentrations. There were no FT × DOF interactions ( ≥ 0.21) for insulin area under the curve (iAUC), insulin:glucose ratio, insulin or glucose baseline, or peak insulin or glucose concentrations. At 21 DOF, steers fed CrP had decreased glucose area under the curve (gAUC; = 0.01), decreased glucose clearance rate (; = 0.02), and increased glucose half-life (T; = 0.07) compared to steers fed Cont; however, by 98 DOF, no differences were observed between treatments. At 98 DOF, all steers, regardless of treatment, had increased ( effect on growth performance. With increased DOF, all steers became more insulin resistant, using more insulin to clear less glucose, and these effects were not mitigated by CrP supplementation. PMID:26812328

  15. Endocrinization of FGF1 produces a neomorphic and potent insulin sensitizer

    OpenAIRE

    Suh, Jae Myoung; Jonker, Johan W.; Ahmadian, Maryam; Goetz, Regina; Lackey, Denise; Osborn, Olivia; Huang, Zifeng; Liu, Weilin; Yoshihara, Eiji; van Dijk, Theo; Havinga, Rick; Fan, Weiwei; Yin, Yun-Qiang; Yu, Ruth T.; Liddle, Christopher

    2014-01-01

    FGF1 is an autocrine/paracrine regulator whose binding to heparan sulfate proteoglycans effectively precludes its circulation 1,2 . Though known as a mitogenic factor, FGF1 knockout mice develop insulin resistance when stressed by a high fat diet, suggesting a potential role in nutrient homeostasis 3,4 . Here we show that parenteral delivery of a single dose of recombinant FGF1 (rFGF1) results in potent, insulin-dependent glucose lowering in diabetic mice that is dose-dependent, but does not ...

  16. Pioglitazone Upregulates Angiotensin Converting Enzyme 2 Expression in Insulin-Sensitive Tissues in Rats with High-Fat Diet-Induced Nonalcoholic Steatohepatitis

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2014-01-01

    Full Text Available Background and Aim. Thiazolidinediones (TZDs can improve hepatic steatosis in nonalcoholic steatohepatitis (NASH. Angiotensin (Ang II, the primary effector of renin-angiotensin system (RAS, plays vital roles in the development and progression of NASH. And some AngII-mediated effects can be regulated by TZDs. Angiotensin-converting enzyme (ACE 2, a new component of RAS, can degrade Ang II to attenuate its subsequent physiological actions. We aimed to evaluate the effects of TZDs on ACE2 expression in insulin-sensitive tissues in NASH rats. Methods. Forty rats were divided into the normal control, high-fat diet (HFD, pioglitazone control, and HFD plus pioglitazone groups. After 24 weeks of treatment, we evaluated changes in liver histology and tissue-specific ACE2 expression. Results. ACE2 gene and protein expression was significantly greater in liver and adipose tissue in the HFD group compared with normal control group, while was significantly reduced in skeletal muscle. Pioglitazone significantly reduced the degree of hepatic steatosis compared with the HFD group. Pioglitazone significantly increased ACE2 protein expression in liver, adipose tissue, and skeletal muscle compared with the HFD group. Conclusions. Pioglitazone improves hepatic steatosis in the rats with HFD-induced NASH and upregulates ACE2 expression in insulin-sensitive tissues.

  17. Rapamycin has a biphasic effect on insulin sensitivity in C2C12 myotubes due to sequential disruption of mTORC1 and mTORC2

    Directory of Open Access Journals (Sweden)

    Lan eYe

    2012-09-01

    Full Text Available Rapamycin, an inhibitor of mTOR complex 1 (mTORC1, improves insulin sensitivity in acute studies in vitro and in vivo by disrupting a negative feedback loop mediated by S6 kinase. We find that rapamycin has a clear biphasic effect on insulin sensitivity in C2C12 myotubes, with enhanced responsiveness during the first hour that declines to almost complete insulin resistance by 24-48 hours. We and others have recently observed that chronic rapamycin treatment induces insulin resistance in rodents, at least in part due to disruption of mTORC2, an mTOR-containing complex that is not acutely sensitive to the drug. Chronic rapamycin treatment may also impair insulin action via the inhibition of mTORC1-dependent mitochondrial biogenesis and activity, which could result in a buildup of lipid intermediates that are known to trigger insulin resistance. We confirmed that rapamycin inhibits expression of PGC-1α, a key mitochondrial transcription factor, and acutely reduces respiration rate in myotubes. However, rapamycin did not stimulate phosphorylation of PKCθ, a central mediator of lipid-induced insulin resistance. Instead, we found dramatic disruption of mTORC2, which coincided with the onset of insulin resistance. Selective inhibition of mTORC1 or mTORC2 by shRNA-mediated knockdown of specific components (Raptor and Rictor, respectively confirmed that mitochondrial effects of rapamycin are mTORC1-dependent, whereas insulin resistance was recapitulated only by knockdown of mTORC2. Thus, mTORC2 disruption, rather than inhibition of mitochondria, causes insulin resistance in rapamycin-treated myotubes, and this system may serve as a useful model to understand the effects of rapamycin on mTOR signaling in vivo.

  18. Insulin Resistance and Hyperinsulinemia

    OpenAIRE

    Kim, Sun H.; Reaven, Gerald M

    2008-01-01

    OBJECTIVE—Recently, it has been suggested that insulin resistance and hyperinsulinemia can exist in isolation and have differential impacts on cardiovascular disease (CVD). To evaluate this suggestion, we assessed the degree of discordance between insulin sensitivity and insulin response in a healthy, nondiabetic population. RESEARCH DESIGN AND METHODS—Insulin sensitivity was quantified by determining the steady-state plasma glucose (SSPG) concentration during an insulin suppression test in 4...

  19. Activity-sensitive signaling by muscle-derived insulin-like growth factors in the developing and regenerating neuromuscular system.

    Science.gov (United States)

    Caroni, P

    1993-08-27

    In the nervous system, activity-sensitive retrograde signaling pathways couple the status of postsynaptic activation to elimination of collaterals during development and collateral sprouting in the adult. This article presents evidence supporting the hypothesis that in the neuromuscular system, skeletal muscle fiber derived insulin-like growth factors play a central role in such signaling. This evidence includes (1) timing and activity-sensitive expression of IGFs in skeletal muscle fibers, (2) identification of an IGF- and activity-sensitive retrograde signaling pathway from developing muscle to motoneurons in the spinal cord, (3) demonstration that IGFs in the muscle are both sufficient and necessary to induce interstitial cell proliferation and intramuscular nerve sprouting in adult muscle.

  20. 5-HT2CRs expressed by pro-opiomelanocortin neurons regulate insulin sensitivity in liver

    Science.gov (United States)

    Mice lacking 5-HT 2C receptors displayed hepatic insulin resistance, a phenotype normalized by re-expression of 5-HT2CRs only in pro-opiomelanocortin (POMC) neurons. 5-HT2CR deficiency also abolished the anti-diabetic effects of meta-chlorophenylpiperazine (a 5-HT2CR agonist); these effects were re...

  1. Effect of antioxidant supplementation on insulin sensitivity in response to endurance exercise training

    DEFF Research Database (Denmark)

    Yfanti, Christina; Nielsen, Anders R; Åkerström, Thorbjörn;

    2011-01-01

    . To assess the effect of antioxidant supplementation during endurance training on insulin-stimulated glucose uptake, twenty-one young healthy (age 29±1 y; BMI 25±3 Kg m(-2)) men were randomly assigned into either an antioxidant (AO; 500 mg vitamin C and 400 IU vitamin E (a-tocopherol) daily) or a placebo (PL...

  2. Endocrinization of FGF1 produces a neomorphic and potent insulin sensitizer

    NARCIS (Netherlands)

    Suh, Jae Myoung; Jonker, Johan W; Ahmadian, Maryam; Goetz, Regina; Lackey, Denise; Osborn, Olivia; Huang, Zhifeng; Liu, Weilin; Yoshihara, Eiji; van Dijk, Theo H; Havinga, Rick; Fan, Weiwei; Yin, Yun-Qiang; Yu, Ruth T; Liddle, Christopher; Atkins, Annette R; Olefsky, Jerrold M; Mohammadi, Moosa; Downes, Michael; Evans, Ronald M

    2014-01-01

    Fibroblast growth factor 1 (FGF1) is an autocrine/paracrine regulator whose binding to heparan sulphate proteoglycans effectively precludes its circulation. Although FGF1 is known as a mitogenic factor, FGF1 knockout mice develop insulin resistance when stressed by a high-fat diet, suggesting a pote

  3. TEA INCREASES INSULIN SENSITIVITY AND DECREASES OXIDATIVE STRESS IN RATS WITH METABOLIC SYNDROME

    Science.gov (United States)

    Cinnamon has been shown to improve glycemic control in people with non-insulin dependent diabetes. Fifty-one patients with gestational diabetes diagnosed between 24 and 32 weeks of gestation were randomized to 6 weeks of either 1 gram of cinnamon per day or an identical-appearing capsule containing...

  4. Site-specific covalent modifications of human insulin by catechol estrogens: Reactivity and induced structural and functional changes.

    Science.gov (United States)

    Ku, Ming-Chun; Fang, Chieh-Ming; Cheng, Juei-Tang; Liang, Huei-Chen; Wang, Tzu-Fan; Wu, Chih-Hsing; Chen, Chiao-Chen; Tai, Jung-Hsiang; Chen, Shu-Hui

    2016-01-01

    Proteins, covalently modified by catechol estrogens (CEs), were identified recently from the blood serum of diabetic patients and referred to as estrogenized proteins. Estrogenization of circulating insulin may occur and affect its molecular functioning. Here, the chemical reactivity of CEs towards specific amino acid residues of proteins and the structural and functional changes induced by the estrogenization of insulin were studied using cyclic voltammetry, liquid chromatography-mass spectrometry, circular dichroism spectroscopy, molecular modeling, and bioassays. Our results indicate that CEs, namely, 2- and 4-hydroxyl estrogens, were thermodynamically and kinetically more reactive than the catechol moiety. Upon co-incubation, intact insulin formed a substantial number of adducts with one or multiple CEs via covalent conjugation at its Cys 7 in the A or B chain, as well as at His10 or Lys29 in the B chain. Such conjugation was coupled with the cleavage of inter-chain disulfide linkages. Estrogenization on these sites may block the receptor-binding pockets of insulin. Insulin signaling and glucose uptake levels were lower in MCF-7 cells treated with modified insulin than in cells treated with native insulin. Taken together, our findings demonstrate that insulin molecules are susceptible to active estrogenization, and that such modification may alter the action of insulin. PMID:27353345

  5. Site-specific covalent modifications of human insulin by catechol estrogens: Reactivity and induced structural and functional changes

    Science.gov (United States)

    Ku, Ming-Chun; Fang, Chieh-Ming; Cheng, Juei-Tang; Liang, Huei-Chen; Wang, Tzu-Fan; Wu, Chih-Hsing; Chen, Chiao-Chen; Tai, Jung-Hsiang; Chen, Shu-Hui

    2016-06-01

    Proteins, covalently modified by catechol estrogens (CEs), were identified recently from the blood serum of diabetic patients and referred to as estrogenized proteins. Estrogenization of circulating insulin may occur and affect its molecular functioning. Here, the chemical reactivity of CEs towards specific amino acid residues of proteins and the structural and functional changes induced by the estrogenization of insulin were studied using cyclic voltammetry, liquid chromatography-mass spectrometry, circular dichroism spectroscopy, molecular modeling, and bioassays. Our results indicate that CEs, namely, 2- and 4-hydroxyl estrogens, were thermodynamically and kinetically more reactive than the catechol moiety. Upon co-incubation, intact insulin formed a substantial number of adducts with one or multiple CEs via covalent conjugation at its Cys 7 in the A or B chain, as well as at His10 or Lys29 in the B chain. Such conjugation was coupled with the cleavage of inter-chain disulfide linkages. Estrogenization on these sites may block the receptor-binding pockets of insulin. Insulin signaling and glucose uptake levels were lower in MCF-7 cells treated with modified insulin than in cells treated with native insulin. Taken together, our findings demonstrate that insulin molecules are susceptible to active estrogenization, and that such modification may alter the action of insulin.

  6. Streamflow sensitivity to water storage changes across Europe

    Science.gov (United States)

    Berghuijs, Wouter; Hartmann, Andreas; Woods, Ross

    2016-04-01

    Terrestrial water storage is the primary source of river flow. We introduce storage sensitivity of streamflow, which for a given flow rate indicates the relative change in streamflow per change in catchment water storage. Storage sensitivity of streamflow can be directly derived from streamflow observations. Analysis of 725 catchments in Europe reveals that storage sensitivity of streamflow is high in e.g. parts of Spain, England, Germany and Denmark, whereas flow regimes in parts of the Alps are more resilient (that is, less sensitive) to storage changes. A comparison of storage sensitivity of streamflow with observations suggests that storage sensitivity of streamflow is a significant control on the regional differences in variability of low, median, and high flow conditions. Streamflow sensitivity provides new guidance for a changing hydrosphere where groundwater abstraction and climatic changes are altering water storage and flow regimes.

  7. Curcumin rescues high fat diet-induced obesity and insulin sensitivity in mice through regulating SREBP pathway.

    Science.gov (United States)

    Ding, Lili; Li, Jinmei; Song, Baoliang; Xiao, Xu; Zhang, Binfeng; Qi, Meng; Huang, Wendong; Yang, Li; Wang, Zhengtao

    2016-08-01

    Obesity and its major co-morbidity, type 2 diabetes, have reached an alarming epidemic prevalence without an effective treatment available. It has been demonstrated that inhibition of SREBP pathway may be a useful strategy to treat obesity with type 2 diabetes. Sterol regulatory element-binding proteins (SREBPs) are major transcription factors regulating the expression of genes involved in biosynthesis of cholesterol, fatty acid and triglyceride. In current study, we identified a small molecule, curcumin, inhibited the SREBP expression in vitro. The inhibition of SREBP by curcumin decreased the biosynthesis of cholesterol and fatty acid. In vivo, curcumin ameliorated HFD-induced body weight gain and fat accumulation in liver or adipose tissues, and improved serum lipid levels and insulin sensitivity in HFD-induced obese mice. Consistently, curcumin regulates SREBPs target genes and metabolism associated genes in liver or adipose tissues, which may directly contribute to the lower lipid level and improvement of insulin resistance. Take together, curcumin, a major active component of Curcuma longa could be a potential leading compound for development of drugs for the prevention of obesity and insulin resistance. PMID:27208389

  8. 7-week aerobic exercise training reduces adipocyte area and improves insulin sensitivity in Wistar rats fed a highly palatable diet

    OpenAIRE

    Nádia F. Garcia; Carmem P. Valgas da Silva; Maycon Jr Ferreira; Leandro K. Oharomari; Thalita Rocha; Camila de Moraes

    2016-01-01

    Abstract The aim of this study was to evaluate the effect aerobic exercise training on fat pad mass, adipocyte size, leptin release and insulin sensitivity in rats fed with high fat-palatable diet. Twenty-four male Wistar rats (250-260g) were divided into four groups: sedentary control (CTR/SD), trained control (CTR/TR), obese sedentary (OB/SD) and obese trained (OB/TR). Obese groups were fed with high fat-palatable diet (27% of fat) and control groups fed with AIN-93. Our results showed that...

  9. Knockdown of DAPIT (Diabetes-associated Protein in Insulin-sensitive Tissue) Results in Loss of ATP Synthase in Mitochondria

    OpenAIRE

    Ohsakaya, Shigenori; Fujikawa, Makoto; Hisabori, Toru; Yoshida, Masasuke

    2011-01-01

    It was found recently that a diabetes-associated protein in insulin-sensitive tissue (DAPIT) is associated with mitochondrial ATP synthase. Here, we report that the suppressed expression of DAPIT in DAPIT-knockdown HeLa cells causes loss of the population of ATP synthase in mitochondria. Consequently, DAPIT-knockdown cells show smaller mitochondrial ATP synthesis activity, slower growth in normal medium, and poorer viability in glucose-free medium than the control cells. The mRNA levels of α-...

  10. Effect of a 1-week, eucaloric, moderately high-fat diet on peripheral insulin sensitivity in healthy premenopausal women

    OpenAIRE

    Branis, Natalia M.; Etesami, Marjan; Walker, Ryan W.; Berk, Evan S; Albu, Jeanine B.

    2015-01-01

    Objectives To determine whether a weight-maintaining, moderate (50%) high-fat diet is deleterious to insulin sensitivity in healthy premenopausal women. Design/setting/participants 23 African-American and non-Hispanic white, healthy, overweight, and obese premenopausal women recruited in New York City, USA, fed either a eucaloric, 1-week long high-fat (50% of total Kcal from fat) diet or a eucaloric, 1-week long low-fat (30% of total Kcal from fat) diet, assigned in a randomized crossover des...

  11. Low whole-body insulin sensitivity in patients with ischaemic heart disease is associated with impaired myocardial glucose uptake predictive of poor outcome after revascularisation

    International Nuclear Information System (INIS)

    We tested the hypothesis that low whole-body insulin sensitivity in patients with ischaemic heart disease and impaired left ventricular (LV) function is associated with abnormalities of insulin-mediated myocardial glucose uptake affecting outcome after coronary bypass surgery (CABG). We studied 29 patients with ischaemic heart disease and impaired LV ejection fraction (EF) and age-matched healthy volunteers (n=30). As assessed by euglycaemic glucose-insulin clamp, 15 patients had a low and 14 a normal whole-body insulin sensitivity. Using positron emission tomography, patterns of fluorine-18 fluorodeoxyglucose and nitrogen-13 ammonia uptake in addition to quantified glucose uptake, blood flow and hyperaemic blood flow were assessed before CABG in 16 myocardial segments of the left ventricle. Major adverse cardiac events and LVEF were evaluated 7 months after CABG. Glucose uptake in normokinetic PET-normal myocardium was found to be higher in patients with normal whole-body insulin sensitivity (P<0.001), whereas in patients with low whole-body insulin sensitivity more segments displayed a pattern of reduced glucose uptake in normoperfused myocardium (PET-reverse mismatch) (P<0.05). Hyperaemic blood flow was impaired in both patient groups. A major cardiac event after CABG could partly be predicted by the LV extent of normoperfused segments with PET-reverse mismatch. We conclude that low whole-body insulin sensitivity in patients with ischaemic heart disease and impaired LV function is associated with impaired insulin-mediated myocardial glucose uptake, which is partially predictive of a worse outcome after CABG. (orig.)

  12. Indices of insulin sensitivity and secretion from a standard liquid meal test in subjects with type 2 diabetes, impaired or normal fasting glucose

    Directory of Open Access Journals (Sweden)

    Farmer Mildred V

    2009-05-01

    Full Text Available Abstract Background To provide an initial evaluation of insulin sensitivity and secretion indices derived from a standard liquid meal tolerance test protocol in subjects with normal (NFG, impaired fasting glucose (IFG or type 2 diabetes mellitus. Methods Areas under the curve (AUC for glucose, insulin and C-peptide from pre-meal to 120 min after consumption of a liquid meal were calculated, as were homeostasis model assessments of insulin resistance (HOMA2-IR and the Matsuda index of insulin sensitivity. Results Subjects with NFG (n = 19, IFG (n = 19, and diabetes (n = 35 had mean ± SEM HOMA2-IR values of 1.0 ± 0.1, 1.6 ± 0.2 and 2.5 ± 0.3 and Matsuda insulin sensitivity index values of 15.6 ± 2.0, 8.8 ± 1.2 and 6.0 ± 0.6, respectively. The log-transformed values for these variables were highly correlated overall and within each fasting glucose category (r = -0.91 to -0.94, all p Conclusion These results provide initial evidence to support the usefulness of a standard liquid meal tolerance test for evaluation of insulin secretion and sensitivity in clinical and population studies.

  13. Glutamate Cysteine Ligase—Modulatory Subunit Knockout Mouse Shows Normal Insulin Sensitivity but Reduced Liver Glycogen Storage

    KAUST Repository

    Lavoie, Suzie

    2016-04-21

    Glutathione (GSH) deficits have been observed in several mental or degenerative illness, and so has the metabolic syndrome. The impact of a decreased glucose metabolism on the GSH system is well-known, but the effect of decreased GSH levels on the energy metabolism is unclear. The aim of the present study was to investigate the sensitivity to insulin in the mouse knockout (KO) for the modulatory subunit of the glutamate cysteine ligase (GCLM), the rate-limiting enzyme of GSH synthesis. Compared to wildtype (WT) mice, GCLM-KO mice presented with reduced basal plasma glucose and insulin levels. During an insulin tolerance test, GCLM-KO mice showed a normal fall in glycemia, indicating normal insulin secretion. However, during the recovery phase, plasma glucose levels remained lower for longer in KO mice despite normal plasma glucagon levels. This is consistent with a normal counterregulatory hormonal response but impaired mobilization of glucose from endogenous stores. Following a resident-intruder stress, during which stress hormones mobilize glucose from hepatic glycogen stores, KO mice showed a lower hyperglycemic level despite higher plasma cortisol levels when compared to WT mice. The lower hepatic glycogen levels observed in GCLM-KO mice could explain the impaired glycogen mobilization following induced hypoglycemia. Altogether, our results indicate that reduced liver glycogen availability, as observed in GCLM-KO mice, could be at the origin of their lower basal and challenged glycemia. Further studies will be necessary to understand how a GSH deficit, typically observed in GCLM-KO mice, leads to a deficit in liver glycogen storage.

  14. Lemon detox diet reduced body fat, insulin resistance, and serum hs-CRP level without hematological changes in overweight Korean women.

    Science.gov (United States)

    Kim, Mi Joung; Hwang, Jung Hyun; Ko, Hyun Ji; Na, Hye Bock; Kim, Jung Hee

    2015-05-01

    The lemon detox program is a very low-calorie diet which consists of a mixture of organic maple and palm syrups, and lemon juice for abstinence period of 7 days. We hypothesized that the lemon detox program would reduce body weight, body fat mass, thus lowering insulin resistance and known risk factors of cardiovascular disease. We investigated anthropometric indices, insulin sensitivity, levels of serum adipokines, and inflammatory markers in overweight Korean women before and after clinical intervention trial. Eighty-four premenopausal women were randomly divided into 3 groups: a control group without diet restriction (Normal-C), a pair-fed placebo diet group (Positive-C), and a lemon detox diet group (Lemon-D). The intervention period was 11 days total: 7 days with the lemon detox juice or the placebo juice, and then 4 days with transitioning food. Changes in body weight, body mass index, percentage body fat, and waist-hip ratio were significantly greater in the Lemon-D and Positive-C groups compared to the Normal-C group. Serum insulin level, homeostasis model assessment insulin resistance scores, leptin, and adiponectin levels decreased in the Lemon-D and Positive-C groups. Serum high-sensitive C-reactive protein (hs-CRP) levels were also reduced only in the Lemon-D group. Hemoglobin and hematocrit levels remained stable in the Lemon-D group while they decreased in the Positive-C and Normal-C groups. Therefore, we suppose that the lemon detox program reduces body fat and insulin resistance through caloric restriction and might have a potential beneficial effect on risk factors for cardiovascular disease related to circulating hs-CRP reduction without hematological changes. PMID:25912765

  15. The Dual Amylin- and Calcitonin-Receptor Agonist KBP-042 Increases Insulin Sensitivity and Induces Weight Loss in Rats with Obesity

    DEFF Research Database (Denmark)

    Hjuler, Sara Toftegaard; Gydesen, Sofie; Andreassen, Kim Vietz;

    2016-01-01

    Objective: In this study, KBP-042, a dual amylin- and calcitonin-receptor agonist, was investigated as a treatment of obesity and insulin resistance in five different doses (0.625 μg/kg-10 μg/kg) compared with saline-treated and pair-fed controls. Methods: Rats with obesity received daily s...... combines two highly relevant features, namely weight loss and insulin sensitivity, and is thus an excellent candidate for chronic treatment of obesity and insulin resistance........c. administrations for 56 days, and glucose tolerance was assessed after one acute injection, 3 weeks of treatment, and again after 7 weeks of treatment. To assess the effect on insulin sensitivity, rats received 5 μg/kg KBP-042 for 21 days before hyperinsulinemic-euglycemic clamp. Results: KBP-042 induced a...

  16. Long-chain omega-3 fatty acids regulate bovine whole-body protein metabolism by promoting muscle insulin signalling to the Akt-mTOR-S6K1 pathway and insulin sensitivity.

    Science.gov (United States)

    Gingras, Andrée-Anne; White, Phillip James; Chouinard, P Yvan; Julien, Pierre; Davis, Teresa A; Dombrowski, Luce; Couture, Yvon; Dubreuil, Pascal; Myre, Alexandre; Bergeron, Karen; Marette, André; Thivierge, M Carole

    2007-02-15

    The ability of the skeletal musculature to use amino acids to build or renew constitutive proteins is gradually lost with age and this is partly due to a decline in skeletal muscle insulin sensitivity. Since long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) from fish oil are known to improve insulin-mediated glucose metabolism in insulin-resistant states, their potential role in regulating insulin-mediated protein metabolism was investigated in this study. Experimental data are based on a switchback design composed of three 5 week experimental periods using six growing steers to compare the effect of a continuous abomasal infusion of LCn-3PUFA-rich menhaden oil with an iso-energetic control oil mixture. Clamp and insulin signalling observations were combined with additional data from a second cohort of six steers. We found that enteral LCn-3PUFA potentiate insulin action by increasing the insulin-stimulated whole-body disposal of amino acids from 152 to 308 micromol kg(-1) h(-1) (P=0.006). The study further showed that in the fed steady-state, chronic adaptation to LCn-3PUFA induces greater activation (P<0.05) of the Akt-mTOR-S6K1 signalling pathway. Simultaneously, whole-body total flux of phenylalanine was reduced from 87 to 67 micromol kg(-1) h(-1) (P=0.04) and oxidative metabolism was decreased (P=0.05). We conclude that chronic feeding of menhaden oil provides a novel nutritional mean to enhance insulin-sensitive aspects of protein metabolism. PMID:17158167

  17. Long-chain omega-3 fatty acids regulate bovine whole-body protein metabolism by promoting muscle insulin signalling to the Akt–mTOR–S6K1 pathway and insulin sensitivity

    Science.gov (United States)

    Gingras, Andrée-Anne; White, Phillip James; Chouinard, P Yvan; Julien, Pierre; Davis, Teresa A; Dombrowski, Luce; Couture, Yvon; Dubreuil, Pascal; Myre, Alexandre; Bergeron, Karen; Marette, André; Thivierge, M Carole

    2007-01-01

    The ability of the skeletal musculature to use amino acids to build or renew constitutive proteins is gradually lost with age and this is partly due to a decline in skeletal muscle insulin sensitivity. Since long-chain omega-3 polyunsaturated fatty acids (LCn–3PUFA) from fish oil are known to improve insulin-mediated glucose metabolism in insulin-resistant states, their potential role in regulating insulin-mediated protein metabolism was investigated in this study. Experimental data are based on a switchback design composed of three 5 week experimental periods using six growing steers to compare the effect of a continuous abomasal infusion of LCn–3PUFA-rich menhaden oil with an iso-energetic control oil mixture. Clamp and insulin signalling observations were combined with additional data from a second cohort of six steers. We found that enteral LCn–3PUFA potentiate insulin action by increasing the insulin-stimulated whole-body disposal of amino acids from 152 to 308 μmol kg−1 h−1 (P = 0.006). The study further showed that in the fed steady-state, chronic adaptation to LCn–3PUFA induces greater activation (P < 0.05) of the Akt–mTOR–S6K1 signalling pathway. Simultaneously, whole-body total flux of phenylalanine was reduced from 87 to 67 μmol kg−1 h−1 (P = 0.04) and oxidative metabolism was decreased (P = 0.05). We conclude that chronic feeding of menhaden oil provides a novel nutritional mean to enhance insulin-sensitive aspects of protein metabolism. PMID:17158167

  18. Insulin-sensitizing and Anti-proliferative Effects of Argania spinosa Seed Extracts

    Directory of Open Access Journals (Sweden)

    Samira Samane

    2006-01-01

    Full Text Available Argania spinosa is an evergreen tree endemic of southwestern Morocco. Many preparations have been used in traditional Moroccan medicine for centuries to treat several illnesses including diabetes. However, scientific evidence supporting these actions is lacking. Therefore, we prepared various extracts of the argan fruit, namely keel, cake and argan oil extracts, which we tested in the HTC hepatoma cell line for their potential to affect cellular insulin responses. Cell viability was measured by Trypan Blue exclusion and the response to insulin evaluated by the activation of the extracellular regulated kinase (ERK1/2, ERK kinase (MEK1/2 and protein kinase B (PKB/Akt signaling components. None of the extracts demonstrated significant cytotoxic activity. Certain extracts demonstrated a bi-phasic effect on ERK1/2 activation; low doses of the extract slightly increased ERK1/2 activation in response to insulin, whereas higher doses completely abolished the response. In contrast, none of the extracts had any significant effect on MEK whereas only a cake saponin subfraction enhanced insulin-induced PKB/Akt activation. The specific action of argan oil extracts on ERK1/2 activation made us consider an anti-proliferative action. We have thus tested other transformed cell lines (HT-1080 and MSV-MDCK-INV cells and found similar results. Inhibition of ERK1/2 activation was also associated with decreased DNA synthesis as evidenced by [3H]thymidine incorporation experiments. These results suggest that the products of Argania spinosa may provide a new therapeutic avenue against proliferative diseases.

  19. Insulin-sensitizing and anti-proliferative effects of Argania spinosa seed extracts.

    Science.gov (United States)

    Samane, Samira; Noël, Josette; Charrouf, Zoubida; Amarouch, Hamid; Haddad, Pierre Selim

    2006-09-01

    Argania spinosa is an evergreen tree endemic of southwestern Morocco. Many preparations have been used in traditional Moroccan medicine for centuries to treat several illnesses including diabetes. However, scientific evidence supporting these actions is lacking. Therefore, we prepared various extracts of the argan fruit, namely keel, cake and argan oil extracts, which we tested in the HTC hepatoma cell line for their potential to affect cellular insulin responses. Cell viability was measured by Trypan Blue exclusion and the response to insulin evaluated by the activation of the extracellular regulated kinase (ERK1/2), ERK kinase (MEK1/2) and protein kinase B (PKB/Akt) signaling components. None of the extracts demonstrated significant cytotoxic activity. Certain extracts demonstrated a bi-phasic effect on ERK1/2 activation; low doses of the extract slightly increased ERK1/2 activation in response to insulin, whereas higher doses completely abolished the response. In contrast, none of the extracts had any significant effect on MEK whereas only a cake saponin subfraction enhanced insulin-induced PKB/Akt activation. The specific action of argan oil extracts on ERK1/2 activation made us consider an anti-proliferative action. We have thus tested other transformed cell lines (HT-1080 and MSV-MDCK-INV cells) and found similar results. Inhibition of ERK1/2 activation was also associated with decreased DNA synthesis as evidenced by [(3)H]thymidine incorporation experiments. These results suggest that the products of Argania spinosa may provide a new therapeutic avenue against proliferative diseases.

  20. Adiponectin in mice with altered growth hormone action: links to insulin sensitivity and longevity?

    OpenAIRE

    Lubbers, Ellen R; List, Edward O.; Jara, Adam; Sackman-Sala, Lucila; Cordoba-Chacon, Jose; Gahete, Manuel D.; Kineman, Rhonda D.; Boparai, Ravneet; Bartke, Andrzej; Kopchick, John J.; Berryman, Darlene E.

    2013-01-01

    Adiponectin is positively correlated with longevity and negatively correlated with many obesity-related diseases. While there are several circulating forms of adiponectin, the high molecular weight (HMW) version has been suggested to have the predominant bioactivity. Adiponectin gene expression and cognate serum protein levels are of particular interest in mice with altered growth hormone (GH) signaling as these mice exhibit extremes in obesity that are positively associated with insulin sens...

  1. Insulin-sensitizing and anti-proliferative effects of Argania spinosa seed extracts.

    Science.gov (United States)

    Samane, Samira; Noël, Josette; Charrouf, Zoubida; Amarouch, Hamid; Haddad, Pierre Selim

    2006-09-01

    Argania spinosa is an evergreen tree endemic of southwestern Morocco. Many preparations have been used in traditional Moroccan medicine for centuries to treat several illnesses including diabetes. However, scientific evidence supporting these actions is lacking. Therefore, we prepared various extracts of the argan fruit, namely keel, cake and argan oil extracts, which we tested in the HTC hepatoma cell line for their potential to affect cellular insulin responses. Cell viability was measured by Trypan Blue exclusion and the response to insulin evaluated by the activation of the extracellular regulated kinase (ERK1/2), ERK kinase (MEK1/2) and protein kinase B (PKB/Akt) signaling components. None of the extracts demonstrated significant cytotoxic activity. Certain extracts demonstrated a bi-phasic effect on ERK1/2 activation; low doses of the extract slightly increased ERK1/2 activation in response to insulin, whereas higher doses completely abolished the response. In contrast, none of the extracts had any significant effect on MEK whereas only a cake saponin subfraction enhanced insulin-induced PKB/Akt activation. The specific action of argan oil extracts on ERK1/2 activation made us consider an anti-proliferative action. We have thus tested other transformed cell lines (HT-1080 and MSV-MDCK-INV cells) and found similar results. Inhibition of ERK1/2 activation was also associated with decreased DNA synthesis as evidenced by [(3)H]thymidine incorporation experiments. These results suggest that the products of Argania spinosa may provide a new therapeutic avenue against proliferative diseases. PMID:16951716

  2. Insulin-sensitizing and Anti-proliferative Effects of Argania spinosa Seed Extracts

    OpenAIRE

    Samira Samane; Josette Noël; Zoubida Charrouf; Hamid Amarouch; Pierre Selim Haddad

    2006-01-01

    Argania spinosa is an evergreen tree endemic of southwestern Morocco. Many preparations have been used in traditional Moroccan medicine for centuries to treat several illnesses including diabetes. However, scientific evidence supporting these actions is lacking. Therefore, we prepared various extracts of the argan fruit, namely keel, cake and argan oil extracts, which we tested in the HTC hepatoma cell line for their potential to affect cellular insulin responses. Cell viability was measu...

  3. Association of obesity risk SNPs in PCSK1 with insulin sensitivity and proinsulin conversion

    OpenAIRE

    Häring Hans-Ulrich; Staiger Harald; Stefan Norbert; Machicao Fausto; Thamer Claus; Ketterer Caroline; Schäfer Silke A; Haupt Axel; Heni Martin; Fritsche Andreas

    2010-01-01

    Abstract Background Prohormone convertase 1 is involved in maturation of peptides. Rare mutations in gene PCSK1, encoding this enzyme, cause childhood obesity and abnormal glucose homeostasis with elevated proinsulin concentrations. Common single nucleotide polymorphisms (SNPs) within this gene, rs6232 and rs6235, are associated with obesity. We studied whether these SNPs influence the prediabetic traits insulin resistance, β-cell dysfunction, or glucose intolerance. Methods We genotyped 1498...

  4. Gender Differences in Skeletal Muscle Substrate Metabolism – Molecular Mechanisms and Insulin Sensitivity

    OpenAIRE

    Lundsgaard, Anne-Marie; Kiens, Bente

    2014-01-01

    It has become increasingly apparent that substrate metabolism is subject to gender-specific regulation, and the aim of this review is to outline the available evidence of molecular gender differences in glucose and lipid metabolism of skeletal muscle. Female sex has been suggested to have a favorable effect on glucose homeostasis, and the available evidence from hyperinsulinemic–euglycemic clamp studies is summarized to delineate whether there is a gender difference in whole-body insulin sens...

  5. Gender differences in skeletal muscle substrate metabolism - molecular mechanisms and insulin sensitivity

    OpenAIRE

    Anne-Marie eLundsgaard; Bente eKiens

    2014-01-01

    It has become increasingly apparent that substrate metabolism is subject to gender specific regulation, and the aim of this review is to outline the available evidence of molecular gender differences in glucose and lipid metabolism of skeletal muscle. Female sex has been suggested to have a favorable effect on glucose homeostasis, and the available evidence from hyperinsulinemic-euglycemic clamp studies is summarized to delineate whether there is a gender difference in whole body insulin sens...

  6. The role of skeletal muscle glycogen breakdown for regulation of insulin sensitivity by exercise

    Directory of Open Access Journals (Sweden)

    Jørgen eJensen

    2011-12-01

    Full Text Available Glycogen is the storage form of carbohydrates in mammals. In humans the majority of glycogen is stored in skeletal muscles (~500 g and the liver (~100 g. Food is supplied in larger meals, but the blood glucose concentration has to be kept within narrow limits to survive and stay healthy. Therefore, the body has to cope with periods of excess carbohydrates and periods without supplementation. Healthy persons remove blood glucose rapidly when glucose is in excess, but insulin-stimulated glucose disposal is reduced in insulin resistant and type 2 diabetic subjects. During a hyperinsulinemic euglycaemic clamp, 70-90 % of glucose disposal will be stored as muscle glycogen in healthy subjects. The glycogen stores in skeletal muscles are limited because an efficient feedback-mediated inhibition of glycogen synthase prevents accumulation. De novo lipid synthesis can contribute to glucose disposal when glycogen stores are filled. Exercise physiologists normally consider glycogen’s main function as energy substrate. Glycogen is the main energy substrate during exercise intensity above 70 % of maximal oxygen uptake (VO2max and fatigue develops when the glycogen stores are depleted in the active muscles. After exercise, the rate of glycogen synthesis is increased to replete glycogen stores, and blood glucose is the substrate. Indeed insulin-stimulated glucose uptake and glycogen synthesis is elevated after exercise, which, from an evolutional point of view, will favour glycogen repletion and preparation for new fight or flight events. In the modern society, the reduced glycogen stores in skeletal muscles after exercise allows carbohydrates to be stored as muscle glycogen and prevents that glucose is channelled to de novo lipid synthesis, which over time will causes ectopic fat accumulation and insulin resistance. The reduction of skeletal muscle glycogen after exercise allows a healthy storage of carbohydrates after meals and prevents development of type

  7. The effect of strength and endurance training on insulin sensitivity and fat distribution in human immunodeficiency virus-infected patients with lipodystrophy

    DEFF Research Database (Denmark)

    Lindegaard, B; Hansen, T; Hvid, T;

    2008-01-01

    CONTEXT: Fat redistribution, insulin resistance, and low-grade inflammation characterize HIV-infected patients with lipodystrophy. Currently, no effective therapies exist for the combined treatment of fat redistribution and insulin resistance. OBJECTIVE: Our objective was to evaluate the effects...... of strength and endurance training on insulin sensitivity and fat distribution in HIV-infected patients with lipodystrophy. SUBJECTS AND METHODS: Twenty sedentary HIV-infected men with lipodystrophy were randomly assigned to supervised strength or endurance training three times a week for 16 wk. The primary...... and increased high-density lipoprotein cholesterol (P lipodystrophy....

  8. Diapause is associated with a change in the polarity of secretion of insulin-like peptides.

    Science.gov (United States)

    Matsunaga, Yohei; Honda, Yoko; Honda, Shuji; Iwasaki, Takashi; Qadota, Hiroshi; Benian, Guy M; Kawano, Tsuyoshi

    2016-01-01

    The insulin/IGF-1 signalling (IIS) pathway plays an important role in the regulation of larval diapause, the long-lived growth arrest state called dauer arrest, in Caenorhabditis elegans. In this nematode, 40 insulin-like peptides (ILPs) have been identified as putative ligands of the IIS pathway; however, it remains unknown how ILPs modulate larval diapause. Here we show that the secretory polarity of INS-35 and INS-7, which suppress larval diapause, is changed in the intestinal epithelial cells at larval diapause. These ILPs are secreted from the intestine into the body cavity during larval stages. In contrast, they are secreted into the intestinal lumen and degraded during dauer arrest, only to be secreted into the body cavity again when the worms return to developmental growth. The process that determines the secretory polarity of INS-35 and INS-7, thus, has an important role in the modulation of larval diapause. PMID:26838180

  9. Naringenin Inhibits Adipogenesis and Reduces Insulin Sensitivity and Adiponectin Expression in Adipocytes

    Directory of Open Access Journals (Sweden)

    Allison J. Richard

    2013-01-01

    Full Text Available Adipose tissue development and function are widely studied to examine the relationship between obesity and the metabolic syndrome. It is well documented that the inability of adipose tissue to properly increase its lipid storage capacity during the obese state can lead to metabolic dysfunction. In a blind screen of 425 botanicals, we identified naringenin as an inhibitor of adipocyte differentiation. Naringenin is one of the most abundant citrus flavonoids, and recent studies have demonstrated antihyperlipidemic capabilities. These studies have largely focused on the effects of naringenin on the liver. Our biochemical studies clearly demonstrate that naringenin inhibits adipogenesis and impairs mature fat cell function. Naringenin specifically inhibited adipogenesis in a dose-dependent fashion as judged by examining lipid accumulation and induction of adipocyte marker protein expression. In mature 3T3-L1 adipocytes, naringenin reduced the ability of insulin to induce IRS-1 tyrosine phosphorylation and substantially inhibited insulin-stimulated glucose uptake in a dose-dependent manner and over a time frame of 1.5 to 24 hours. Exposure to naringenin also inhibited adiponectin protein expression in mature murine and human adipocytes. Our studies have revealed that naringenin may have a negative impact on adipocyte-related diseases by limiting differentiation of preadipocytes, by significantly inducing insulin resistance, and by decreasing adiponectin expression in mature fat cells.

  10. PKCδ regulates hepatic insulin sensitivity and hepatosteatosis in mice and humans

    DEFF Research Database (Denmark)

    Bezy, Olivier; Tran, Thien T; Pihlajamäki, Jussi;

    2011-01-01

    C57BL/6J and 129S6/Sv (B6 and 129) mice differ dramatically in their susceptibility to developing diabetes in response to diet- or genetically induced insulin resistance. A major locus contributing to this difference has been mapped to a region on mouse chromosome 14 that contains the gene encodi...... of PKCδ between strains of mice and in obese humans play an important role in the genetic risk of hepatic insulin resistance, glucose intolerance, and hepatosteatosis; and thus PKCδ may be a potential target in the treatment of metabolic syndrome.......C57BL/6J and 129S6/Sv (B6 and 129) mice differ dramatically in their susceptibility to developing diabetes in response to diet- or genetically induced insulin resistance. A major locus contributing to this difference has been mapped to a region on mouse chromosome 14 that contains the gene encoding...... PKCδ. Here, we found that PKCδ expression in liver was 2-fold higher in B6 versus 129 mice from birth and was further increased in B6 but not 129 mice in response to a high-fat diet. PRKCD gene expression was also elevated in obese humans and was positively correlated with fasting glucose...

  11. The effect of a diiodothyronine mimetic on insulin sensitivity in male cardiometabolic patients: a double-blind randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Fleur van der Valk

    Full Text Available BACKGROUND AND AIMS: Obesity and its associated cardiometabolic co-morbidities are increasing worldwide. Since thyroid hormone mimetics are capable of uncoupling the beneficial metabolic effects of thyroid hormones from their deleterious effects on heart, bone and muscle, this class of drug is considered as adjacent therapeutics to weight-lowering strategies. This study investigated the safety and efficacy of TRC150094, a thyroid hormone mimetic. MATERIALS AND METHODS: This 4-week, randomized, placebo-controlled, double-blind trial was conducted in India and The Netherlands. Forty subjects were randomized at a 1:1 ratio to receive either TRC150094 dosed at 50 mg or placebo once daily for 4 weeks. Hyperinsulinemic euglycemic clamp and (1H-Magnetic Resonance Spectroscopy (MRS were performed before and after treatment. RESULTS: At baseline, subjects were characterized by markedly impaired hepatic and peripheral insulin sensitivity. TRC150094 dosed 50 mg once daily was safe and well tolerated. Hepatic nor peripheral insulin sensitivity improved after TRC150094 treatment, expressed as the suppression of Endogenous Glucose Production from 59.5 to 62.1%; p = 0.477, and the rate of glucose disappearance from 28.8 to 26.4 µmol kg(-1min(-1, p = 0.185. TRC150094 administration did not result in differences in fasting plasma free fatty acids from 0.51 to 0.51 mmol/L, p = 0.887 or in insulin-mediated suppression of lipolysis from 57 to 54%, p = 0.102. Also, intrahepatic triglyceride content was unaltered. CONCLUSION: Collectively, these data show that, in contrast to the potent metabolic effects in experimental models, TRC150094 at a dose of 50 mg daily does not improve the metabolic homeostasis in subjects at an increased cardiometabolic risk. Further studies are needed to evaluate whether TRC150094 has beneficial effects in patients with more severe metabolic derangement, such as overt diabetes mellitus and hypertriglyceridemia. TRIAL REGISTRATION

  12. Effects of changes in acid base and calcium concentration on fasting serum insulin, proinsulin, and glucose concentrations.

    OpenAIRE

    Smellie, W S; O'Donnell, J; Davidson, H.; Couper, J; Logue, F. C.

    1994-01-01

    AIMS--To test the hypothesis that alterations in acid base or calcium concentration may affect proinsulin processing or the insulin secretion mechanism. METHODS--Changes in proinsulin secretion or cleavage were assessed by measuring serum intact proinsulin and immunoreactive insulin concentrations in three models of acid base and calcium disturbance: (1) subacute changes in acid base status in six volunteers who received oral placebo, ammonium chloride, or sodium bicarbonate for three five da...

  13. Surgical removal of visceral fat decreases plasma free fatty acid and increases insulin sensitivity on liver and peripheral tissue in monosodium glutamate (MSG)-obese rats.

    OpenAIRE

    Kim, Y. W.; Kim, J. Y.; Lee, S K

    1999-01-01

    In order to evaluate the role of visceral and subcutaneous fat tissue in insulin sensitivity and lipid metabolism, we measured the fasting levels of plasma free fatty acid (FFA) and insulin, glucose disappearance rate (Rd), and hepatic glucose production rate (HGP) after surgical removal of visceral (VF) or subcutaneous (SF) fat tissue in monosodium glutamate-obese (MSG-Ob) rats. Monosodium glutamate obesity was induced in rats by neonatal injection of MSG. Surgery to remove fat was done at 1...

  14. Acupoint-Specific, Frequency-Dependent, and Improved Insulin Sensitivity Hypoglycemic Effect of Electroacupuncture Applied to Drug-Combined Therapy Studied by a Randomized Control Clinical Trial

    Directory of Open Access Journals (Sweden)

    Rong-Tsung Lin

    2014-01-01

    Full Text Available The application of electroacupuncture (EA to specific acupoints can induce a hypoglycemic effect in streptozotocin-induced rats, normal rats, and rats with steroid-induced insulin resistance. EA combined with the oral insulin sensitizer rosiglitazone improved insulin sensitivity in rats and humans with type II diabetes mellitus (DM. There are different hypoglycemic mechanisms between Zhongwan and Zusanli acupoints by EA stimulation. On low-frequency (2 Hz stimulation at bilateral Zusanli acupoints, serotonin was involved in the hypoglycemic effect in normal rats. Moreover, after 15 Hz EA stimulation at the bilateral Zusanli acupoints, although enhanced insulin activity mainly acts on the insulin-sensitive target organs, the muscles must be considered. In addition, 15 Hz EA stimulation at the bilateral Zusanli acupoints has the combined effect of enhancing cholinergic nerve activity and increasing nitric oxide synthase (NOS activity to enhance insulin activity. Despite the well-documented effect of pain control by EA in many systemic diseases, there are few high-quality long-term clinical trials on the hypoglycemic effect of EA in DM. Combination treatment with EA and other medications seems to be an alternative treatment to achieve better therapeutic goals that merit future investigation.

  15. Sensitivity and Strength: Effects of Instructions on Resistance to Change

    Science.gov (United States)

    Podlesnik, Christopher A.; Chase, Philip N.

    2006-01-01

    Several research laboratories have found that instructed behavior can be less sensitive to changes in contingencies than shaped behavior. The current experiment examined whether these differences in sensitivity could be related to resistance to change. Two groups of subjects, who were matched on the basis of an initial disruption assessment, were…

  16. Creosote Bush (Larrea tridentata) Improves Insulin Sensitivity and Reduces Plasma and Hepatic Lipids in Hamsters Fed a High Fat and Cholesterol Diet

    Science.gov (United States)

    Del Vecchyo-Tenorio, Georgina; Rodríguez-Cruz, Maricela; Andrade-Cetto, Adolfo; Cárdenas-Vázquez, René

    2016-01-01

    Creosote bush, Larrea tridentata (Sesse y Moc. Ex DC, Zygophyllaceae) is a shrub found in the deserts of Northern Mexico and Southwestern United States. In traditional medicine, it is used to treat a variety of illnesses including type 2 diabetes. The present study aims to investigate the effects of creosote bush ethanolic extract on plasma and liver parameters associated with the metabolic syndrome in hamsters fed a high fat and cholesterol diet (HFD), comparing them with those induced by ezetimibe (EZ). Seven groups of six hamsters each were formed. Six groups were fed HFD for 2 weeks. The following 2 weeks, the HFD groups received: (1) only HFD, (2) HFD + 3 mg% EZ, (3) HFD + 0.2% creosote bush ethanolic extract, (4) only standard diet (Std Diet), (5) Std Diet + 3 mg% EZ, (6) Std Diet + 0.2% creosote bush ethanolic extract. The beneficial effects of creosote bush ethanolic extract in the HFD hamster model were a reduction of insulin resistance, associated with lower serum insulin and leptin, lower hepatic lipid peroxidation and higher liver antioxidant capacity. Plasma and liver lipids tended or were reduced to values closer to those of animals fed standard diet. A similar effect on lipids was induced by EZ, although with even lower hepatic cholesterol and total lipids concentrations. In general, the change from HFD to standard diet plus ethanolic extract induced the same but deeper changes, including a reduction in plasma glucose and an increase in the percentage of HDL cholesterol. Unlike creosote bush extract, EZ increased food consumption and neutral fecal steroids, with no significant effect on body weight, epididymal fat pads, liver peroxidation or antioxidant capacity. Also EZ did not modify serum insulin and leptin. However, insulin sensitivity improved to values similar to those induced by the extract. This suggests that the mechanism of action of creosote bush ethanolic extract is different to inhibition of cholesterol absorption or increase excretion

  17. Creosote Bush (Larrea tridentata) Improves Insulin Sensitivity and Reduces Plasma and Hepatic Lipids in Hamsters Fed a High Fat and Cholesterol Diet.

    Science.gov (United States)

    Del Vecchyo-Tenorio, Georgina; Rodríguez-Cruz, Maricela; Andrade-Cetto, Adolfo; Cárdenas-Vázquez, René

    2016-01-01

    Creosote bush, Larrea tridentata (Sesse y Moc. Ex DC, Zygophyllaceae) is a shrub found in the deserts of Northern Mexico and Southwestern United States. In traditional medicine, it is used to treat a variety of illnesses including type 2 diabetes. The present study aims to investigate the effects of creosote bush ethanolic extract on plasma and liver parameters associated with the metabolic syndrome in hamsters fed a high fat and cholesterol diet (HFD), comparing them with those induced by ezetimibe (EZ). Seven groups of six hamsters each were formed. Six groups were fed HFD for 2 weeks. The following 2 weeks, the HFD groups received: (1) only HFD, (2) HFD + 3 mg% EZ, (3) HFD + 0.2% creosote bush ethanolic extract, (4) only standard diet (Std Diet), (5) Std Diet + 3 mg% EZ, (6) Std Diet + 0.2% creosote bush ethanolic extract. The beneficial effects of creosote bush ethanolic extract in the HFD hamster model were a reduction of insulin resistance, associated with lower serum insulin and leptin, lower hepatic lipid peroxidation and higher liver antioxidant capacity. Plasma and liver lipids tended or were reduced to values closer to those of animals fed standard diet. A similar effect on lipids was induced by EZ, although with even lower hepatic cholesterol and total lipids concentrations. In general, the change from HFD to standard diet plus ethanolic extract induced the same but deeper changes, including a reduction in plasma glucose and an increase in the percentage of HDL cholesterol. Unlike creosote bush extract, EZ increased food consumption and neutral fecal steroids, with no significant effect on body weight, epididymal fat pads, liver peroxidation or antioxidant capacity. Also EZ did not modify serum insulin and leptin. However, insulin sensitivity improved to values similar to those induced by the extract. This suggests that the mechanism of action of creosote bush ethanolic extract is different to inhibition of cholesterol absorption or increase excretion

  18. OSL sensitivity changes during single aliquot procedures: Computer simulations

    DEFF Research Database (Denmark)

    McKeever, S.W.S.; Agersnap Larsen, N.; Bøtter-Jensen, L.;

    1997-01-01

    We present computer simulations of sensitivity changes obtained during single aliquot, regeneration procedures. The simulations indicate that the sensitivity changes are the combined result of shallow trap and deep trap effects. Four separate processes have been identified. Although procedures can...... be suggested to eliminate the shallow trap effects, it appears that the deep trap effects cannot be removed. The character of the sensitivity changes which result from these effects is seen to be dependent upon several external parameters, including the extent of bleaching of the OSL signal, the laboratory...... dose used and the natural dose. However, the sensitivity changes appear only weakly dependent upon added dose, suggesting that the SARA single aliquot technique may be a suitable method to overcome the sensitivity changes. (C) 1997 Elsevier Science Ltd....

  19. Green tea extract decreases oxidative stress and improves insulin sensitivity in an animal model of insulin resistance, the fructose- fed rat

    Science.gov (United States)

    Metabolic syndrome is characterized by insulin resistance, dyslipidemia, and increased oxidative stress. Tea polyphenols, as both insulin potentiating factors and antioxidants, might act in preventing the metabolic syndrome. We aimed to determine the effects of green tea extract consumption on oxida...

  20. Trigonella foenum-graecum water extract improves insulin sensitivity and stimulates PPAR and γ gene expression in high fructose-fed insulin-resistant rats

    Directory of Open Access Journals (Sweden)

    Abbas Mohammadi

    2016-01-01

    Conclusion: This study demonstrates the beneficial effects of trigonella foenum-graecum extract on insulin resistance in rats fed on a high-fructose diet. At least three mechanisms are involved, including direct insulin-like effect, increase in adiponectin levels, and PPARγ protein expression.

  1. Ursolic acid and rosiglitazone combination improves insulin sensitivity by increasing the skeletal muscle insulin-stimulated IRS-1 tyrosine phosphorylation in high-fat diet-fed C57BL/6J mice.

    Science.gov (United States)

    Sundaresan, Arjunan; Radhiga, Thangaiyan; Pugalendi, Kodukkur Viswanathan

    2016-06-01

    The aim of this present study was to investigate the effect of ursolic acid (UA) and rosiglitazone (RSG) on insulin sensitivity and proximal insulin signaling pathways in high-fat diet (HFD)-fed C57/BL/6J mice. Male C57BL/6J mice were fed either normal diet or HFD for 10 weeks, after which animals in each dietary group were divided into the following six groups (normal diet, normal diet plus UA and RSG, HFD alone, HFD plus UA, HFD plus RSG, and HFD plus UA and RSG) for the next 5 weeks. UA (5 mg/kg BW) and RSG (4 mg/kg BW) were administered as suspensions directly into the stomach using a gastric tube. The HFD diet elevated fasting plasma glucose, insulin, and homeostasis model assessment index. The expression of insulin receptor substrate (IRS)-1, phosphoinositide 3-kinase (PI3-kinase), Akt, and glucose transporter (GLUT) 4 were determined by Western blot analyses. The results demonstrated that combination treatment (UA/RSG) ameliorated HFD-induced glucose intolerance and insulin resistance by improving the homeostatic model assessment (HOMA) index. Further, combination treatment (UA/RSG) stimulated the IRS-1, PI3-kinase, Akt, and GLUT 4 translocation. These results strongly suggest that combination treatment (UA/RSG) activates IRS-PI3-kinase-Akt-dependent signaling pathways to induce GLUT 4 translocation and increases the expression of insulin receptor to improve glucose intolerance.

  2. A study on lifestyle adjustment and insulin sensitizing treatment in PCOS-IR women

    Institute of Scientific and Technical Information of China (English)

    Ma Liang-kun; Jin Li-na; Yu Qi; Xu Ling

    2008-01-01

    Objective:To compare the efficacy of lifestyle adjustment,metformin and rosiglitazone on women with polycystic ovary syndrome and insulin resistance(PCOS-IR)Methods:A randomized controlled trial(RCT)was carried out in Peking Union Medical College Hospital(PUMCH),One hundred and six women with PCOS were randomly allocated to three intervention groups:lifestyle adjustment,lifestyle adjustment plus metformin,lifestyle adjustment plus rosiglitazone group,patients were treated with lifestyle adjustment(diet and exercise),lifestyle adjustment plus metformin(500mg three times daily),lifestyle adjustment plus rosiglitazone(4mg once daily)for three months.Sixty patients completed treatments,basal body temperature(BBT),total testosterone as well as fasting serum insulin and lipid levels were measured and compared in all patients before and after lifestyle adjustment.Results:No significant differences were found in the baseline characteristics among three groups.In lifestyle adjustment group 51%(22/43)patients completed treatment,23%(5/22)patients resumed ovulation.In lifestyle adjustment plus metformin group 58%(21/36)patients completed treatment,43%(9/21)patients resumed ovulation.In lifestyle adjustment plus rosiglitazone group 63%(17/27)patients completed treatment,59%(10/17)patients resumed ovulation.Ovulation rate was significantly higher in lifestyle adjustment plus rosiglitazone group than that in weight loss group.There was no significant difference among three groups in body mass index(BMI),waist circumference,waist-hip ratio(WHR),sex hormone,serum fasting insulin and lipid levels after treatment.Conclusions:Lifestyle adjustment,metformin and rosiglitazone treatment can improve ovulation each.

  3. Dominant inhibitory adipocyte-specific secretory factor (ADSF)/resistin enhances adipogenesis and improves insulin sensitivity

    OpenAIRE

    Kim, Kee-Hong; Zhao, Ling; Moon, Yangsoo; Kang, Chulho; Sul, Hei Sook

    2004-01-01

    Adipocyte-specific secretory factor (ADSF)/resistin is a small cysteine-rich protein secreted from adipose tissue that belongs to a gene family found in inflammatory zone (FIZZ) or found in resistin-like molecule (RELM). ADSF has been implicated in modulating adipogenesis and insulin resistance. To examine the long-term function of ADSF in adipogenesis and glucose homeostasis, we constructed an expression vector for a dominant inhibitory form of ADSF by fusing it to the human IgGγ constant re...

  4. The Prostaglandin E2 Receptor EP4 Regulates Obesity-Related Inflammation and Insulin Sensitivity.

    Directory of Open Access Journals (Sweden)

    Mika Yasui

    Full Text Available With increasing body weight, macrophages accumulate in adipose tissue. There, activated macrophages secrete numerous proinflammatory cytokines and chemokines, giving rise to chronic inflammation and insulin resistance. Prostaglandin E2 suppresses macrophage activation via EP4; however, the role of EP4 signaling in insulin resistance and type 2 diabetes mellitus remains unknown. In this study, we treated db/db mice with an EP4-selective agonist, ONO-AE1-329, for 4 weeks to explore the role of EP4 signaling in obesity-related inflammation in vivo. Administration of the EP4 agonist did not affect body weight gain or food intake; however, in the EP4 agonist-treated group, glucose tolerance and insulin resistance were significantly improved over that of the vehicle-treated group. Additionally, administration of the EP4 agonist inhibited the accumulation of F4/80-positive macrophages and the formation of crown-like structures in white adipose tissue, and the adipocytes were significantly smaller. The treatment of the EP4 agonist increased the number of anti-inflammatory M2 macrophages, and in the stromal vascular fraction of white adipose tissue, which includes macrophages, it markedly decreased the levels of proinflammatory cytokines and chemokines. Further, EP4 activation increased the expression of adiponectin and peroxidase proliferator-activated receptors in white adipose tissue. Next, we examined in vitro M1/M2 polarization assay to investigate the impact of EP4 signaling on determining the functional phenotypes of macrophages. Treatment with EP4 agonist enhanced M2 polarization in wild-type peritoneal macrophages, whereas EP4-deficient macrophages were less susceptible to M2 polarization. Notably, antagonizing peroxidase proliferator-activated receptor δ activity suppressed EP4 signaling-mediated shift toward M2 macrophage polarization. Thus, our results demonstrate that EP4 signaling plays a critical role in obesity-related adipose tissue

  5. Sex-different control of hepatic metabolism in relation to insulin sensitivity

    OpenAIRE

    Gustavsson, Carolina

    2010-01-01

    The liver is a key metabolic organ. The liver has adapted to the different metabolic needs in men and women, and therefore responds in a sex-specific manner to various stimuli. Specific genes have recently been related to the development of hepatic insulin resistance (IR) and with our improved knowledge of sex-differences in fuel metabolism, it may be postulated that the liver has a crucial role in sex-dependent development of IR. To improve the prevention and treatment of hepatic IR, a bette...

  6. Aleglitazar, a dual peroxisome proliferator-activated receptor-α/γ agonist, improves insulin sensitivity, glucose control and lipid levels in people with type 2 diabetes: findings from a randomized, double-blind trial.

    Science.gov (United States)

    Stirban, A O; Andjelkovic, M; Heise, T; Nosek, L; Fischer, A; Gastaldelli, A; Herz, M

    2016-07-01

    The present single-centre, randomized, double-blind, placebo-controlled phase II study investigated the effect of the balanced dual peroxisome proliferator-activated receptor-α/γ agonist aleglitazar on whole-body and liver insulin sensitivity, β-cell function and other components of cardiometabolic syndrome after 16 weeks of treatment in patients with type 2 diabetes inadequately controlled with metformin monotherapy who received once-daily 150 µg aleglitazar or matching placebo as add-on therapy to metformin. Baseline and 16-week assessments included a two-step hyperinsulinaemic-euglycaemic clamp, followed by a hyperglycaemic clamp, as well as evaluation of glycated haemoglobin (HbA1c), lipids and safety variables. The primary endpoint was change in whole-body insulin sensitivity (M-value) from baseline compared with placebo, derived from the second clamp step. M-value improved significantly from baseline with aleglitazar (n = 16) compared with placebo (n = 24; p = 0.05 for difference between arms). We found statistically significant treatment differences with aleglitazar versus placebo in fasting hepatic insulin resistance index (p = 0.01), and in total glucose disposal (p = 0.03) at the second insulin infusion step. Aleglitazar treatment resulted in significant improvements in HbA1c and lipids and was well tolerated. PMID:26663152

  7. Beneficial role of vitamin K supplementation on insulin sensitivity, glucose metabolism, and the reduced risk of type 2 diabetes: A review.

    Science.gov (United States)

    Manna, Prasenjit; Kalita, Jatin

    2016-01-01

    Micronutrients are gaining acceptance as an important nutritional therapy for the prevention and/or management of diabetes and its associated health risks. Although a very small quantity of micronutrients are required for specific functions in our bodies, moderate deficiencies can lead to serious health issues. Impaired insulin sensitivity and glucose intolerance play a major role in the development of diabetic pathophysiology. Vitamin K is well known for its function in blood coagulation. Moreover, several human studies reported the beneficial role of vitamin K supplementation in improving insulin sensitivity and glucose tolerance, preventing insulin resistance, and reducing the risk of type 2 diabetes (T2 D). Both animal and human studies have suggested that vitamin K-dependent protein (osteocalcin [OC]), regulation of adipokine levels, antiinflammatory properties, and lipid-lowering effects may mediate the beneficial function of vitamin K in insulin sensitivity and glucose tolerance. This review for the first time provides an overview of the currently available preclinical and clinical evidences on the effect of vitamin K supplementation in the management of insulin sensitivity and glucose tolerance. The outcome of this review will increase understanding for the development of a novel adjuvant therapy to achieve better control of glycemia and improve the lives of diabetic patients.

  8. Beneficial role of vitamin K supplementation on insulin sensitivity, glucose metabolism, and the reduced risk of type 2 diabetes: A review.

    Science.gov (United States)

    Manna, Prasenjit; Kalita, Jatin

    2016-01-01

    Micronutrients are gaining acceptance as an important nutritional therapy for the prevention and/or management of diabetes and its associated health risks. Although a very small quantity of micronutrients are required for specific functions in our bodies, moderate deficiencies can lead to serious health issues. Impaired insulin sensitivity and glucose intolerance play a major role in the development of diabetic pathophysiology. Vitamin K is well known for its function in blood coagulation. Moreover, several human studies reported the beneficial role of vitamin K supplementation in improving insulin sensitivity and glucose tolerance, preventing insulin resistance, and reducing the risk of type 2 diabetes (T2 D). Both animal and human studies have suggested that vitamin K-dependent protein (osteocalcin [OC]), regulation of adipokine levels, antiinflammatory properties, and lipid-lowering effects may mediate the beneficial function of vitamin K in insulin sensitivity and glucose tolerance. This review for the first time provides an overview of the currently available preclinical and clinical evidences on the effect of vitamin K supplementation in the management of insulin sensitivity and glucose tolerance. The outcome of this review will increase understanding for the development of a novel adjuvant therapy to achieve better control of glycemia and improve the lives of diabetic patients. PMID:27133809

  9. Effect of Probiotic (VSL#3 and Omega-3 on Lipid Profile, Insulin Sensitivity, Inflammatory Markers, and Gut Colonization in Overweight Adults: A Randomized, Controlled Trial

    Directory of Open Access Journals (Sweden)

    Hemalatha Rajkumar

    2014-01-01

    Full Text Available To evaluate the effects of probiotic (VSL#3 and omega-3 fatty acid on insulin sensitivity, blood lipids, and inflammation, we conducted a clinical trial in 60 overweight (BMI>25, healthy adults, aged 40–60 years. After initial screening the subjects were randomized into four groups with 15 per group. The four groups received, respectively, placebo, omega-3 fatty acid, probiotic VSL#3, or both omega-3 and probiotic, for 6 weeks. Blood and fecal samples were collected at baseline and after 6 weeks. The probiotic (VSL#3 supplemented group had significant reduction in total cholesterol, triglyceride, LDL, and VLDL and had increased HDL (P<0.05 value. VSL#3 improved insulin sensitivity (P<0.01, decreased hsCRP, and favorably affected the composition of gut microbiota. Omega-3 had significant effect on insulin sensitivity and hsCRP but had no effect on gut microbiota. Addition of omega-3 fatty acid with VSL#3 had more pronounced effect on HDL, insulin sensitivity and hsCRP. Subjects with low HDL, insulin resistance, and high hsCRP had significantly lower total lactobacilli and bifidobacteria count and higher E. coli and bacteroides count.

  10. High Protein Intake Improves Insulin Sensitivity but Exacerbates Bone Resorption in Immobility (WISE Study)

    Science.gov (United States)

    Heer, Martina; Smith, Scott M.; Frings-Meuthen, Petra; Zwart, Sara R.; Baecker, Natalie

    2012-01-01

    Inactivity, like bed rest (BR), causes insulin resistance (IR) and bone loss even in healthy subjects. High protein intake seems to mitigate this IR but might exacerbate bone loss. We hypothesized that high protein intake (animal:vegetable protein ratio: 60:40), isocaloric, compared to the control group plus high potassium intake would prevent IR without affecting bone turnover. After a 20-day ambulatory adaptation to controlled confinement and diet, 16 women participated in a 60-day, 6 deg head-down-tilt BR and were assigned randomly to one of the two groups. Control subjects (CON, n=8) received 1g/kg body mass/d dietary protein. Nutrition subjects (NUT, n=8) received 1.45g/kg body mass/d dietary protein plus 7.2g branched chain amino acids per day during BR. All subjects received 1670 kcal/d. Bed rest decreased glucose disposal by 35% (pprotein intake prevented insulin resistance, but exacerbated bed rest induced increase in bone resorption markers C-telopeptide (> 30%) and Ntelopeptide (>20%) (both: pprotein intake. We conclude from these results that high protein intake might positively affect glucose tolerance, but might also foster bone loss. Further long-duration studies are mandatory before high protein intake for diabetic patients, who have an increased fracture risk, might be recommended.

  11. The Role of Helicobacter pylori Seropositivity in Insulin Sensitivity, Beta Cell Function, and Abnormal Glucose Tolerance

    Directory of Open Access Journals (Sweden)

    Lou Rose Malamug

    2014-01-01

    Full Text Available Infection, for example, Helicobacter pylori (H. pylori, has been thought to play a role in the pathogenesis of type 2 diabetes mellitus (T2DM. Our aim was to determine the role of H. pylori infection in glucose metabolism in an American cohort. We examined data from 4,136 non-Hispanic white (NHW, non-Hispanic black (NHB, and Mexican Americans (MA aged 18 and over from the NHANES 1999-2000 cohort. We calculated the odds ratios for states of glucose tolerance based on the H. pylori status. We calculated and compared homeostatic model assessment insulin resistance (HOMA-IR and beta cell function (HOMA-B in subjects without diabetes based on the H. pylori status. The results were adjusted for age, body mass index (BMI, poverty index, education, alcohol consumption, tobacco use, and physical activity. The H. pylori status was not a risk factor for abnormal glucose tolerance. After adjustment for age and BMI and also adjustment for all covariates, no difference was found in either HOMA-IR or HOMA-B in all ethnic and gender groups except for a marginally significant difference in HOMA-IR in NHB females. H. pylori infection was not a risk factor for abnormal glucose tolerance, nor plays a major role in insulin resistance or beta cell dysfunction.

  12. Multiple roles for the non-coding RNA SRA in regulation of adipogenesis and insulin sensitivity.

    Directory of Open Access Journals (Sweden)

    Bin Xu

    Full Text Available Peroxisome proliferator-activated receptor-γ (PPARγ is a master transcriptional regulator of adipogenesis. Hence, the identification of PPARγ coactivators should help reveal mechanisms controlling gene expression in adipose tissue development and physiology. We show that the non-coding RNA, Steroid receptor RNA Activator (SRA, associates with PPARγ and coactivates PPARγ-dependent reporter gene expression. Overexpression of SRA in ST2 mesenchymal precursor cells promotes their differentiation into adipocytes. Conversely, knockdown of endogenous SRA inhibits 3T3-L1 preadipocyte differentiation. Microarray analysis reveals hundreds of SRA-responsive genes in adipocytes, including genes involved in the cell cycle, and insulin and TNFα signaling pathways. Some functions of SRA may involve mechanisms other than coactivation of PPARγ. SRA in adipocytes increases both glucose uptake and phosphorylation of Akt and FOXO1 in response to insulin. SRA promotes S-phase entry during mitotic clonal expansion, decreases expression of the cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1, and increases phosphorylation of Cdk1/Cdc2. SRA also inhibits the expression of adipocyte-related inflammatory genes and TNFα-induced phosphorylation of c-Jun NH(2-terminal kinase. In conclusion, SRA enhances adipogenesis and adipocyte function through multiple pathways.

  13. Cinnamon counteracts the negative effects of a high fat/high fructose diet on behavior, brain insulin signaling and Alzheimer-associated changes

    Science.gov (United States)

    Insulin resistance leads to memory impairment. Cinnamon (CN) improves whole body insulin resistance but its effects in the brain are not known. Changes in behavior, insulin signaling, and Alzheimer-associated gene expression in the brain were measured in male Wistar rats fed a high fat/high fructose...

  14. Highly sensitive sensor for picomolar detection of insulin at physiological pH, using GC electrode modified with guanine and electrodeposited nickel oxide nanoparticles.

    Science.gov (United States)

    Salimi, Abdollah; Noorbakhash, Abdollah; Sharifi, Ensieh; Semnani, Abolfazl

    2008-12-01

    The electrochemical behavior of insulin at glassy carbon (GC) electrode modified with nickel oxide nanoparticles and guanine was investigated. Cyclic voltammetry technique has been used for electrodeposition of nickel oxide nanoparticles (NiOx) and immobilization of guanine on the surface GC electrode. In comparison to glassy carbon electrode modified with nickel oxide nanoparticles and bare GC electrode modified with adsorbed guanine, the guanine/nickel oxide nanoparticles/modified GC electrode exhibited excellent catalytic activity for the oxidation of insulin in physiological pH solutions at reduced overpotential. The modified electrode was applied for insulin detection using cyclic voltammetry or hydrodynamic amperometry techniques. It was found that the calibration curve was linear up to 4muM with a detection limit of 22pM and sensitivity of 100.9pA/pM under the optimized condition for hydrodynamic amperometry using a rotating disk modified electrode. In comparison to other electrochemical insulin sensors, this sensor shows many advantages such as simple preparation method without using any special electron transfer mediator or specific reagent, high sensitivity, excellent catalytic activity at physiological pH values, short response time, long-term stability and remarkable antifouling property toward insulin and its oxidation product. Additionally, it is promising for the monitoring of insulin in chromatographic effluents.

  15. Dietary carbohydrate restriction improves insulin sensitivity, blood pressure, microvascular function, and cellular adhesion markers in individuals taking statins.

    Science.gov (United States)

    Ballard, Kevin D; Quann, Erin E; Kupchak, Brian R; Volk, Brittanie M; Kawiecki, Diana M; Fernandez, Maria Luz; Seip, Richard L; Maresh, Carl M; Kraemer, William J; Volek, Jeff S

    2013-11-01

    Statins positively impact plasma low-density lipoprotein cholesterol, inflammation and vascular endothelial function (VEF). Carbohydrate restricted diets (CRD) improve atherogenic dyslipidemia, and similar to statins, have been shown to favorably affect markers of inflammation and VEF. No studies have examined whether a CRD provides additional benefit beyond that achieved by habitual statin use. We hypothesized that a CRD (carb/fat/pro) and averaged across the intervention (11/58/28% carb/fat/pro) demonstrated dietary compliance, with carbohydrate intake at baseline nearly 5-fold greater than during the intervention (P < .001). Compared to baseline, both systolic and diastolic blood pressure decreased after 3 and 6 weeks (P < .01). Peak forearm blood flow, but not flow-mediated dilation, increased at week 6 compared to baseline and week 3 (P ≤ .03). Serum triglyceride, insulin, soluble E-Selectin and intracellular adhesion molecule-1 decreased (P < .01) from baseline at week 3, and this effect was maintained at week 6. In conclusion, these findings demonstrate that individuals undergoing statin therapy experience additional improvements in metabolic and vascular health from a 6 weeks CRD as evidenced by increased insulin sensitivity and resistance vessel endothelial function, and decreased blood pressure, triglycerides, and adhesion molecules. PMID:24176230

  16. Pair feeding-mediated changes in metabolism: stress response and pathophysiology in insulin-resistant, atherosclerosis-prone JCR:LA-cp rats.

    Science.gov (United States)

    Russell, James C; Proctor, Spencer D; Kelly, Sandra E; Brindley, David N

    2008-06-01

    Rats of the JCR:LA-cp strain, which are homozygous for the cp gene (cp/cp), are obese, insulin-resistant, and hyperinsulinemic. They exhibit associated micro- and macrovascular disease and end-stage ischemic myocardial lesions and are highly stress sensitive. We subjected male cp/cp rats to pair feeding (providing the rats each day with the amount of food eaten by matched freely fed animals), a procedure that alters the diurnal feeding pattern, leading to a state of intermittent caloric restriction. Effects on insulin, glucose, and lipid metabolism, response to restraint stress, aortic contractile/relaxant response, and myocardial lesion frequency were investigated. Pair-fed young (12-wk-old) cp/cp rats had lower insulin and glucose levels (basal and following restraint), consistent with increased insulin sensitivity, but a greater increase in plasma nonesterified fatty acids in response to restraint. These effects were unrelated to lipolytic rates in adipose tissue but may be related to reduced fatty acid oxidation in skeletal muscle. Older (24-wk-old) pair-fed cp/cp rats had significantly reduced plasma triglyceride levels, improved micro- and macrovascular function, and reduced severity of ischemic myocardial lesions. These changes indicate a significant amelioration of end-stage disease processes in this animal model and the complexity of metabolic/physiological responses in studies involving alterations in food intake. The effects illustrate the sensitivity of the JCR:LA-cp rat, an animal model for the metabolic syndrome and associated cardiovascular disease, to the environmental and experimental milieu. Similar stress-related mechanisms may play a role in metabolically induced cardiovascular disease in susceptible human beings.

  17. Strength training improves muscle quality and insulin sensitivity in Hispanic older adults with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Naomi Brooks, Jennifer E. Layne, Patricia L. Gordon , Ronenn Roubenoff , Miriam E. Nelson , Carmen Castaneda-Sceppa

    2007-01-01

    Full Text Available Hispanics are at increased risk of morbidity and mortality due to their high prevalence of diabetes and poor glycemic control. Strength training is the most effective lifestyle intervention to increase muscle mass but limited data is available in older adults with diabetes. We determined the influence of strength training on muscle quality (strength per unit of muscle mass, skeletal muscle fiber hypertrophy, and metabolic control including insulin resistance (Homeostasis Model Assessment –HOMA-IR, C-Reactive Protein (CRP, adiponectin and Free Fatty Acid (FFA levels in Hispanic older adults. Sixty-two community-dwelling Hispanics (>55 y with type 2 diabetes were randomized to 16 weeks of strength training plus standard care (ST group or standard care alone (CON group. Skeletal muscle biopsies and biochemical measures were taken at baseline and 16 weeks. The ST group show improved muscle quality (mean±SE: 28±3 vs CON (-4±2, p2 and type II fiber cross-sectional area (720±285µm2 compared to CON (type I: -164±290µm2, p=0.04; and type II: -130±336µm2, p=0.04. This was accompanied by reduced insulin resistance [ST: median (interquartile range -0.7(3.6 vs CON: 0.8(3.8, p=0.05]; FFA (ST: -84±30µmol/L vs CON: 149±48µmol/L, p=0.02; and CRP [ST: -1.3(2.9mg/L vs CON: 0.4(2.3mg/L, p=0.05]. Serum adiponectin increased with ST [1.0(1.8µg/mL] compared to CON [-1.2(2.2µg/mL, p

  18. Relaxation response induces temporal transcriptome changes in energy metabolism, insulin secretion and inflammatory pathways.

    Directory of Open Access Journals (Sweden)

    Manoj K Bhasin

    Full Text Available The relaxation response (RR is the counterpart of the stress response. Millennia-old practices evoking the RR include meditation, yoga and repetitive prayer. Although RR elicitation is an effective therapeutic intervention that counteracts the adverse clinical effects of stress in disorders including hypertension, anxiety, insomnia and aging, the underlying molecular mechanisms that explain these clinical benefits remain undetermined. To assess rapid time-dependent (temporal genomic changes during one session of RR practice among healthy practitioners with years of RR practice and also in novices before and after 8 weeks of RR training, we measured the transcriptome in peripheral blood prior to, immediately after, and 15 minutes after listening to an RR-eliciting or a health education CD. Both short-term and long-term practitioners evoked significant temporal gene expression changes with greater significance in the latter as compared to novices. RR practice enhanced expression of genes associated with energy metabolism, mitochondrial function, insulin secretion and telomere maintenance, and reduced expression of genes linked to inflammatory response and stress-related pathways. Interactive network analyses of RR-affected pathways identified mitochondrial ATP synthase and insulin (INS as top upregulated critical molecules (focus hubs and NF-κB pathway genes as top downregulated focus hubs. Our results for the first time indicate that RR elicitation, particularly after long-term practice, may evoke its downstream health benefits by improving mitochondrial energy production and utilization and thus promoting mitochondrial resiliency through upregulation of ATPase and insulin function. Mitochondrial resiliency might also be promoted by RR-induced downregulation of NF-κB-associated upstream and downstream targets that mitigates stress.

  19. Relaxation response induces temporal transcriptome changes in energy metabolism, insulin secretion and inflammatory pathways.

    Science.gov (United States)

    Bhasin, Manoj K; Dusek, Jeffery A; Chang, Bei-Hung; Joseph, Marie G; Denninger, John W; Fricchione, Gregory L; Benson, Herbert; Libermann, Towia A

    2013-01-01

    The relaxation response (RR) is the counterpart of the stress response. Millennia-old practices evoking the RR include meditation, yoga and repetitive prayer. Although RR elicitation is an effective therapeutic intervention that counteracts the adverse clinical effects of stress in disorders including hypertension, anxiety, insomnia and aging, the underlying molecular mechanisms that explain these clinical benefits remain undetermined. To assess rapid time-dependent (temporal) genomic changes during one session of RR practice among healthy practitioners with years of RR practice and also in novices before and after 8 weeks of RR training, we measured the transcriptome in peripheral blood prior to, immediately after, and 15 minutes after listening to an RR-eliciting or a health education CD. Both short-term and long-term practitioners evoked significant temporal gene expression changes with greater significance in the latter as compared to novices. RR practice enhanced expression of genes associated with energy metabolism, mitochondrial function, insulin secretion and telomere maintenance, and reduced expression of genes linked to inflammatory response and stress-related pathways. Interactive network analyses of RR-affected pathways identified mitochondrial ATP synthase and insulin (INS) as top upregulated critical molecules (focus hubs) and NF-κB pathway genes as top downregulated focus hubs. Our results for the first time indicate that RR elicitation, particularly after long-term practice, may evoke its downstream health benefits by improving mitochondrial energy production and utilization and thus promoting mitochondrial resiliency through upregulation of ATPase and insulin function. Mitochondrial resiliency might also be promoted by RR-induced downregulation of NF-κB-associated upstream and downstream targets that mitigates stress. PMID:23650531

  20. Comparison of the effects of barnidipine+losartan compared with telmisartan+hydrochlorothiazide on several parameters of insulin sensitivity in patients with hypertension and type 2 diabetes mellitus.

    Science.gov (United States)

    Derosa, Giuseppe; Querci, Fabrizio; Franzetti, Ivano; Dario Ragonesi, Pietro; D'Angelo, Angela; Maffioli, Pamela

    2015-10-01

    The aim of this study was to evaluate the effects of barnidipine+losartan compared with telmisartan+hydrochlorothiazide on several parameters of insulin sensitivity in patients with hypertension and type 2 diabetes mellitus. We enrolled 148 normocholesterolemic patients with mild-to-moderate hypertension and type 2 diabetes mellitus. Patients were treated with barnidipine, 20 mg day(-1), in combination with losartan, 100 mg day(-1), or with telmisartan+hydrochlorothiazide, 80/12.5 mg day(-1), for 6 months. We assessed blood pressure (BP) on a monthly basis; additionally, blood samples were collected to assess, at baseline and after 6 months, the following parameters: fasting plasma glucose; glycated hemoglobin; fasting plasma insulin; HOMA index; and some adipocytokines, such as adiponectin (ADN), resistin, leptin, visfatin and vaspin. Patients were also subjected to an euglycemic hyperinsulinemic clamp to assess the M value and glucose infusion rate to ascertain their insulin sensitivity. One hundred and forty-one patients completed the study. The BP was reduced in both groups, although the reduction was greater with barnidipine+losartan (Plosartan increased the M value and glucose infusion rate during the euglycemic hyperinsulinemic clamp (Plosartan (Plosartan compared with baseline (Plosartan were significantly better than those obtained with telmisartan+hydrochlorothiazide (Plosartan improved the insulin sensitivity, as assessed by an euglycemic hyperinsulinemic clamp, and improved some of the adipocytokines related to insulin resistance.

  1. Macrophages and Adipocytes in Human Obesity Adipose Tissue Gene Expression and Insulin Sensitivity During Calorie Restriction and Weight Stabilization

    DEFF Research Database (Denmark)

    Capel, F.; Klimcakova, E.; Viguerie, N.;

    2009-01-01

    OBJECTIVE-We investigated the regulation of adipose tissue gene expression during different phases of a dietary weight loss program and its relation with insulin sensitivity. RESEARCH DESIGN AND METHODS-Twenty-two obese women followed a dietary intervention program composed of an energy restriction...... phase with a 4-week very-low-calorie diet and a weight stabilization period composed of a 2-month low-calorie diet followed by 3-4 months of a weight maintenance diet. At each time point, a euglycemic-hyperinsulinemic clamp and subcutaneous adipose tissue biopsies were performed. Adipose tissue gene...... during the dietary intervention program. Transcriptome profiling revealed two main patterns of variations. The first involved 464 mostly adipocyte genes involved in metabolism that were downregulated during energy restriction, upregulated during weight stabilization, and unchanged during the dietary...

  2. Impact of high-fat, low-carbohydrate diet on myocardial substrate oxidation, insulin sensitivity, and cardiac function after ischemia-reperfusion.

    Science.gov (United States)

    Liu, Jian; Wang, Peipei; Douglas, Samuel L; Tate, Joshua M; Sham, Simon; Lloyd, Steven G

    2016-07-01

    High-fat, low-carbohydrate Diet (HFLCD) impairs the myocardial response to ischemia-reperfusion, but the underlying mechanisms remain elusive. We sought to determine the magnitude of diet-induced alterations in intrinsic properties of the myocardium (including insulin sensitivity and substrate oxidation) and circulating substrate and insulin differences resulting from diet, leading to this impaired response. Rats were fed HFLCD (60% kcal from fat/30% protein/10% carbohydrate) or control diet (CONT) (16%/19%/65%) for 2 wk. Isolated hearts underwent global low-flow ischemia followed by reperfusion (I/R). Carbon-13 NMR spectroscopy was used to determine myocardial substrate TCA cycle entry. Myocardial insulin sensitivity was assessed as dose-response of Akt phosphorylation. There was a significant effect of HFLCD and I/R with both these factors leading to an increase in free fatty acid (FFA) oxidation and a decrease in carbohydrate or ketone oxidation. Following I/R, HFLCD led to decreased ketone and increased FFA oxidation; the recovery of left ventricular (LV) function was decreased in HFLCD and was negatively correlated with FFA oxidation and positively associated with ketone oxidation. HFLCD also resulted in reduced insulin sensitivity. Under physiologic ranges, there were no direct effects of buffer insulin and ketone levels on oxidation of any substrate and recovery of cardiac function after I/R. An insulin-ketone interaction exists for myocardial substrate oxidation characteristics. We conclude that the impaired recovery of function after ischemia-reperfusion with HFLCD is largely due to intrinsic diet effects on myocardial properties, rather than to diet effect on circulating insulin or substrate levels. PMID:27199129

  3. Prokineticin Receptor‐1 Is a New Regulator of Endothelial Insulin Uptake and Capillary Formation to Control Insulin Sensitivity and Cardiovascular and Kidney Functions

    OpenAIRE

    Dormishian, Mojdeh; Turkeri, Gulen; Urayama, Kyoji; Nguyen, Thu Lan; Boulberdaa, Mounia; Messaddeq, Nadia; Renault, Gilles; Henrion, Daniel; Nebigil, Canan G.

    2013-01-01

    Background Reciprocal relationships between endothelial dysfunction and insulin resistance result in a vicious cycle of cardiovascular, renal, and metabolic disorders. The mechanisms underlying these impairments are unclear. The peptide hormones prokineticins exert their angiogenic function via prokineticin receptor‐1 (PKR1). We explored the extent to which endothelial PKR1 contributes to expansion of capillary network and the transcapillary passage of insulin into the heart, kidney, and adip...

  4. The effect of a very low calorie diet on insulin sensitivity, beta cell function, insulin clearance, incretin hormone secretion, androgen levels and body composition in obese young women

    DEFF Research Database (Denmark)

    Svendsen, Pernille F; Jensen, Frank K; Holst, Jens Juul;

    2012-01-01

    Evaluation of the effect of an 8-week very low calorie diet (VLCD, 500-600 kcal daily) on weight, body fat distribution, glucose, insulin and lipid metabolism, androgen levels and incretin secretion in obese women.......Evaluation of the effect of an 8-week very low calorie diet (VLCD, 500-600 kcal daily) on weight, body fat distribution, glucose, insulin and lipid metabolism, androgen levels and incretin secretion in obese women....

  5. The C-174G promoter polymorphism of the IL-6 gene affects energy expenditure and insulin sensitivity.

    Science.gov (United States)

    Kubaszek, Agata; Pihlajamäki, Jussi; Punnonen, Kari; Karhapää, Pauli; Vauhkonen, Ilkka; Laakso, Markku

    2003-02-01

    Interleukin-6 (IL-6) is a pleiotropic cytokine expressed in many tissues. IL-6 null mice show low energy expenditure, but the effect of the variants of the IL-6 gene on energy expenditure has not been previously studied in humans. Therefore, we investigated the effect of the C-174G promoter polymorphism of the IL-6 gene on energy expenditure, measured by indirect calorimetry in healthy Finnish subjects (n = 124). We also measured insulin sensitivity by the hyperinsulinemic-euglycemic clamp. Subjects with the C-174C genotype of the IL-6 gene had significantly lower energy expenditure than subjects with the G-174C or G-174G genotypes both in fasting (CC 13.68 +/- 1.98, CG 14.73 +/- 1.57, GG 14.81 +/- 2.01 kcal x kg(-1) x min(-1); P = 0.012) and during the euglycemic-hyperinsulinemic clamp (CC 15.24 +/- 2.05, CG 16.62 +/- 2.06, GG 16.66 +/- 2.50 kcal x kg(-1) x min(-1); P = 0.007). Moreover, subjects homozygous for the C allele had lower rates of whole-body glucose uptake than carriers of the G allele (CC 50.95 +/- 13.91, CG 59.40 +/- 14.17, GG 59.21 +/- 15.93 micro mol x kg(-1) x min(-1); P = 0.016). The rates of both oxidative (P = 0.013) and nonoxidative (P = 0.016) glucose disposal were significantly affected by the IL-6 promoter polymorphism. In conclusion, the C-174C promoter polymorphism of the IL-6 gene influences energy expenditure and insulin sensitivity in healthy normoglycemic subjects. Whether this polymorphism is a risk factor for obesity or type 2 diabetes can be estimated only in prospective population-based studies.

  6. Long-term treatment with losartan versus atenolol improves insulin sensitivity in hypertension: ICARUS, a LIFE substudy

    DEFF Research Database (Denmark)

    Olsen, Michael H; Fossum, Eigil; Høieggen, Aud;

    2005-01-01

    Hypertension and insulin resistance might be associated through peripheral vascular hypertrophy/rarefaction which compromises skeletal muscle blood flow and decreases glucose uptake, inducing insulin resistance. We hypothesized that treatment with losartan as compared to atenolol would improve...

  7. Effects of consuming fructose- or glucose-sweetened beverages for 10 weeks on lipids, insulin sensitivity and adiposity

    Science.gov (United States)

    Animal studies have documented that, compared with glucose, dietary fructose promotes dyslipidemia and insulin resistance. Experimental evidence that fructose consumption in humans promotes dyslipidemia and insulin resistance compared with glucose consumption has been equivocal. We tested the hypoth...

  8. Overexpression of Insulin Degrading Enzyme could Greatly Contribute to Insulin Down-regulation Induced by Short-Term Swimming Exercise.

    Science.gov (United States)

    Kim, Min Sun; Goo, Jun Seo; Kim, Ji Eun; Nam, So Hee; Choi, Sun Il; Lee, Hye Ryun; Hwang, In Sik; Shim, Sun Bo; Jee, Seung Wan; Lee, Su Hae; Bae, Chang Joon; Cho, Jung Sik; Cho, Jun Yong; Hwang, Dae Youn

    2011-03-01

    Exercise training is highly correlated with the reduced glucose-stimulated insulin secretion (GSIS), although it enhanced insulin sensitivity, glucose uptake and glucose transporter expression to reduce severity of diabetic symptoms. This study investigated the impact of short-term swimming exercise on insulin regulation in the Goto-Kakizaki (GK) rat as a non-obese model of non-insulin-dependent diabetes mellitus. Wistar (W/S) and GK rats were trained 2 hours daily with the swimming exercise for 4 weeks, and then the changes in the metabolism of insulin and glucose were assessed. Body weight was markedly decreased in the exercised GK rats compare to their non-exercised counterpart, while W/S rats did not show any exercise-related changes. Glucose concentration was not changed by exercise, although impaired glucose tolerance was improved in GK rats 120 min after glucose injection. However, insulin concentration was decreased by swimming exercise as in the decrease of GSIS after running exercise. To identify the other cause for exercise-induced insulin down-regulation, the changes in the levels of key factors involved in insulin production (C-peptide) and clearance (insulin-degrading enzyme; IDE) were measured in W/S and GK rats. The C-peptide level was maintained while IDE expression increased markedly. Therefore, these results showed that insulin down-regulation induced by short-term swimming exercise likely attributes to enhanced insulin clearance via IDE over-expression than by altered insulin production.

  9. A Method for Screening Climate Change-Sensitive Infectious Diseases

    OpenAIRE

    Yunjing Wang; Yuhan Rao; Xiaoxu Wu; Hainan Zhao; Jin Chen

    2015-01-01

    Climate change is a significant and emerging threat to human health, especially where infectious diseases are involved. Because of the complex interactions between climate variables and infectious disease components (i.e., pathogen, host and transmission environment), systematically and quantitatively screening for infectious diseases that are sensitive to climate change is still a challenge. To address this challenge, we propose a new statistical indicator, Relative Sensitivity, to identify ...

  10. Insulin resistance and postreceptor changes of liver metabolism in fat-fed mice

    DEFF Research Database (Denmark)

    Hedeskov, Carl Jørgen; Capito, Kirsten; Hansen, Svend Erik;

    1992-01-01

    Medicinsk biokemi, animal diabetes, insulin resistance, postreceptor defects, liver metabolism, high-fat diet......Medicinsk biokemi, animal diabetes, insulin resistance, postreceptor defects, liver metabolism, high-fat diet...

  11. Reduced intestinal lipid absorption and body weight-independent improvements in insulin sensitivity in high-fat diet-fed Park2 knockout mice.

    Science.gov (United States)

    Costa, Diana K; Huckestein, Brydie R; Edmunds, Lia R; Petersen, Max C; Nasiri, Ali; Butrico, Gina M; Abulizi, Abudukadier; Harmon, Daniel B; Lu, Canying; Mantell, Benjamin S; Hartman, Douglas J; Camporez, João-Paulo G; O'Doherty, Robert M; Cline, Gary W; Shulman, Gerald I; Jurczak, Michael J

    2016-07-01

    Mitochondrial dysfunction is associated with many human diseases and results from mismatch of damage and repair over the life of the organelle. PARK2 is a ubiquitin E3 ligase that regulates mitophagy, a repair mechanism that selectively degrades damaged mitochondria. Deletion of PARK2 in multiple in vivo models results in susceptibility to stress-induced mitochondrial and cellular dysfunction. Surprisingly, Park2 knockout (KO) mice are protected from nutritional stress and do not develop obesity, hepatic steatosis or insulin resistance when fed a high-fat diet (HFD). However, these phenomena are casually related and the physiological basis for this phenotype is unknown. We therefore undertook a series of acute HFD studies to more completely understand the physiology of Park2 KO during nutritional stress. We find that intestinal lipid absorption is impaired in Park2 KO mice as evidenced by increased fecal lipids and reduced plasma triglycerides after intragastric fat challenge. Park2 KO mice developed hepatic steatosis in response to intravenous lipid infusion as well as during incubation of primary hepatocytes with fatty acids, suggesting that hepatic protection from nutritional stress was secondary to changes in energy balance due to altered intestinal triglyceride absorption. Park2 KO mice showed reduced adiposity after 1-wk HFD, as well as improved hepatic and peripheral insulin sensitivity. These studies suggest that changes in intestinal lipid absorption may play a primary role in protection from nutritional stress in Park2 KO mice by preventing HFD-induced weight gain and highlight the need for tissue-specific models to address the role of PARK2 during metabolic stress. PMID:27166280

  12. A method for screening climate change-sensitive infectious diseases.

    Science.gov (United States)

    Wang, Yunjing; Rao, Yuhan; Wu, Xiaoxu; Zhao, Hainan; Chen, Jin

    2015-01-01

    Climate change is a significant and emerging threat to human health, especially where infectious diseases are involved. Because of the complex interactions between climate variables and infectious disease components (i.e., pathogen, host and transmission environment), systematically and quantitatively screening for infectious diseases that are sensitive to climate change is still a challenge. To address this challenge, we propose a new statistical indicator, Relative Sensitivity, to identify the difference between the sensitivity of the infectious disease to climate variables for two different climate statuses (i.e., historical climate and present climate) in non-exposure and exposure groups. The case study in Anhui Province, China has demonstrated the effectiveness of this Relative Sensitivity indicator. The application results indicate significant sensitivity of many epidemic infectious diseases to climate change in the form of changing climatic variables, such as temperature, precipitation and absolute humidity. As novel evidence, this research shows that absolute humidity has a critical influence on many observed infectious diseases in Anhui Province, including dysentery, hand, foot and mouth disease, hepatitis A, hemorrhagic fever, typhoid fever, malaria, meningitis, influenza and schistosomiasis. Moreover, some infectious diseases are more sensitive to climate change in rural areas than in urban areas. This insight provides guidance for future health inputs that consider spatial variability in response to climate change. PMID:25594780

  13. A Method for Screening Climate Change-Sensitive Infectious Diseases

    Directory of Open Access Journals (Sweden)

    Yunjing Wang

    2015-01-01

    Full Text Available Climate change is a significant and emerging threat to human health, especially where infectious diseases are involved. Because of the complex interactions between climate variables and infectious disease components (i.e., pathogen, host and transmission environment, systematically and quantitatively screening for infectious diseases that are sensitive to climate change is still a challenge. To address this challenge, we propose a new statistical indicator, Relative Sensitivity, to identify the difference between the sensitivity of the infectious disease to climate variables for two different climate statuses (i.e., historical climate and present climate in non-exposure and exposure groups. The case study in Anhui Province, China has demonstrated the effectiveness of this Relative Sensitivity indicator. The application results indicate significant sensitivity of many epidemic infectious diseases to climate change in the form of changing climatic variables, such as temperature, precipitation and absolute humidity. As novel evidence, this research shows that absolute humidity has a critical influence on many observed infectious diseases in Anhui Province, including dysentery, hand, foot and mouth disease, hepatitis A, hemorrhagic fever, typhoid fever, malaria, meningitis, influenza and schistosomiasis. Moreover, some infectious diseases are more sensitive to climate change in rural areas than in urban areas. This insight provides guidance for future health inputs that consider spatial variability in response to climate change.

  14. Serial change in 123I-MIBG myocardial scintigraphy in non-insulin-dependent diabetes mellitus

    International Nuclear Information System (INIS)

    We performed 123I-MIBG (MIBG) myocardial scintigraphy twice in patients with non-insulin-dependent diabetes mellitus (NIDDM) to investigate whether MIBG distribution was improved by pertinent clinical control. To determine the influential factors for MIBG distribution, we investigated the association between various clinical parameters and the serial change in MIBG uptake parameters. Twenty NIDDM patients with no cardiac disorders were evaluated. Planar images were taken at 30 minutes (early) and 3 hours (delayed) after MIBG injection. The heart-to-upper-mediastinum uptake ratio (H/M) and washout ratio (WR) were calculated as parameters for estimating cardiac sympathetic function. Patients were divided into two groups, eight in the improved group and twelve in the unimproved group, according to the serial change in H/M. The mean interval between the baseline and the follow up study was 2.1±0.6 year. Differences between the means of the laboratory data in patients in both groups were compared for the baseline and the follow up study by using the paired t-test. As a means of determining the influential factors for a serial change of MIBG uptake, Fisher's exact test was performed to evaluate the association between the serial change in cardiac MIBG parameters and changes in other clinical parameters, such as blood sugar (BS) control, BS control method (insulin therapy), serum cholesterol control, and severity of diabetic complications. We also analyzed the association between the changes in CVR-R (coefficient variance of R-R intervals at rest ECG) or NCV (velocity of posterior tibial nerve) and those of other clinical parameters. Associations among these neurological parameters (MIBG parameters, CVR-R and NCV) were also analyzed. Paired t-tests showed a significant decrease in fasting blood sugar and fructosamine in the improved group in the follow up study compared to those in the baseline study. Nevertheless, Fisher's exact test showed no significant association

  15. Low-Frequency Electroacupuncture Improves Insulin Sensitivity in Obese Diabetic Mice through Activation of SIRT1/PGC-1α in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Fengxia Liang

    2011-01-01

    Full Text Available Electroacupuncture (EA has been observed to reduce insulin resistance in obesity and diabetes. However, the biochemical mechanism underlying this effect remains unclear. This study investigated the effects of low-frequency EA on metabolic action in genetically obese and type 2 diabetic db/db mice. Nine-week-old db/m and db/db mice were randomly divided into four groups, namely, db/m, db/m + EA, db/db, and db/db + EA. db/m + EA and db/db + EA mice received 3-Hz electroacupuncture five times weekly for eight consecutive weeks. In db/db mice, EA tempered the increase in fasting blood glucose, food intake, and body mass and maintained insulin levels. In EA-treated db/db mice, improved insulin sensitivity was established through intraperitoneal insulin tolerance test. EA was likewise observed to decrease free fatty acid levels in db/db mice; it increased protein expression in skeletal muscle Sirtuin 1 (SIRT1 and induced gene expression of peroxisome proliferator-activated receptor coactivator (PGC-, nuclear respiratory factor 1 (NRF1, and acyl-CoA oxidase (ACOX. These results indicated that EA offers a beneficial effect on insulin resistance in obese and diabetic db/db mice, at least partly, via stimulation of SIRT1/PGC-, thus resulting in improved insulin signal.

  16. Sense in Sensitivity: Assessing Species Vulnerability to Climate Change

    OpenAIRE

    Mcdougall, Amy

    2013-01-01

    This thesis investigates the impact of future climate change upon species vulnerability. Reports of shifts in species distributions are already numerous, but the pattern of change is not fully understood. This thesis looks to predict which species are likely to be most at risk under climate change and why? This thesis takes the equation; Vulnerability= Sensitivity + Exposure to better discover which species are most vulnerable to climate change. Additionally, this research explores how mitiga...

  17. Liuwei Dihuang Lowers Body Weight and Improves Insulin and Leptin Sensitivity in Obese Rats

    Directory of Open Access Journals (Sweden)

    Benjamin Perry

    2012-01-01

    Full Text Available The present study was aimed at investigating the efficacy and mechanism(s of action of a Chinese herbal formulation, Liuwei Dihuang (LWDH, as a prospective natural weight-lowering product. Following a 2-week acclimation period, 48 obesity-prone (OP-CD rats were divided into 4 groups (n=12 each. One group served as a positive control for obesity (OP, while the other 3 were challenged twice daily by oral gavage with total daily dosages of 500, 1500, or 3500 mg/kg BW LWDH, respectively, for 10 weeks. One group (n=12 of obesity-resistant (OR-CD rats served as the normal control group. All rats were fed the same AIN-93G diet modified to contain 60% energy from fat. The highest LWDH dose significantly reduced body weight during the last 4 weeks of treatment. Food intake was reduced beginning in week 2. The high LWDH dose lowered serum triglyceride (TG and nonesterified fatty acid (NEFA levels and body fat. Both the high and medium doses also lowered serum leptin and insulin levels. Liver function testing revealed no adverse side effects under the current experimental conditions. The results of the present study suggest that LWDH has potential as a preventive or therapeutic natural product against overweight and obesity.

  18. Triglyceride glucose index as a surrogate measure of insulin sensitivity in obese adolescents with normoglycemia, prediabetes, and type 2 diabetes mellitus: Comparison with the hyperinsulinemic–euglycemic clamp

    Science.gov (United States)

    There is a need for simple surrogate estimates of insulin sensitivity in epidemiological studies of obese youth because the hyperinsulinemic-euglycemic clamp is not feasible on a large scale. Objectives: (i) To examine the triglyceride glucose (TyG) index (Ln[fasting triglycerides (mg/dL)'×'fasting ...

  19. Effect of a high monounsaturated fatty acids diet and a Mediterranean diet on serum lipids and insulin sensitivity in adults with mild abdominal obesity

    NARCIS (Netherlands)

    Bos, M.B.; Vries, de J.H.M.; Feskens, E.J.M.; Dijk, van S.J.; Hoelen, D.; Siebelink, E.; Heijligenberg, R.; Groot, de C.P.G.M.

    2010-01-01

    Background and aims - Diets high in monounsaturated fatty acids (MUFA) such as a Mediterranean diet may reduce the risk of cardiovascular diseases by improving insulin sensitivity and serum lipids. Besides being high in MUFA, a Mediterranean diet also contains abundant plant foods, moderate wine and

  20. Insulin sensitivity and lipid profile of eutrophic individuals after acute intake of fresh orange juice in comparison to the commercial-pasteurized orange juice

    Science.gov (United States)

    Citrus flavonoids from orange juice (OJ) have shown hypolipidemic, hypotension, and anti-inflammatory properties. However, the extraction and commercial pasteurization of OJ can influence its nutritional composition in comparison to the fresh squeezed OJ. We evaluated the insulin sensitivity, and th...