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  1. Blueberries’ Impact on Insulin Resistance and Glucose Intolerance

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    April J. Stull

    2016-11-01

    Full Text Available Blueberries are a rich source of polyphenols, which include anthocyanin bioactive compounds. Epidemiological evidence indicates that incorporating blueberries into the diet may lower the risk of developing type 2 diabetes (T2DM. These findings are supported by pre-clinical and clinical studies that have shown improvements in insulin resistance (i.e., increased insulin sensitivity after obese and insulin-resistant rodents or humans consumed blueberries. Insulin resistance was assessed by homeostatic model assessment-estimated insulin resistance (HOMA-IR, insulin tolerance tests, and hyperinsulinemic-euglycemic clamps. Additionally, the improvements in glucose tolerance after blueberry consumption were assessed by glucose tolerance tests. However, firm conclusions regarding the anti-diabetic effect of blueberries cannot be drawn due to the small number of existing clinical studies. Although the current evidence is promising, more long-term, randomized, and placebo-controlled trials are needed to establish the role of blueberries in preventing or delaying T2DM.

  2. Blueberries? Impact on Insulin Resistance and Glucose Intolerance

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    Stull, April J.

    2016-01-01

    Blueberries are a rich source of polyphenols, which include anthocyanin bioactive compounds. Epidemiological evidence indicates that incorporating blueberries into the diet may lower the risk of developing type 2 diabetes (T2DM). These findings are supported by pre-clinical and clinical studies that have shown improvements in insulin resistance (i.e., increased insulin sensitivity) after obese and insulin-resistant rodents or humans consumed blueberries. Insulin resistance was assessed by hom...

  3. Long-term oral exposure to bisphenol A induces glucose intolerance and insulin resistance.

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    Moon, Min Kyong; Jeong, In-Kyong; Jung Oh, Tae; Ahn, Hwa Young; Kim, Hwan Hee; Park, Young Joo; Jang, Hak Chul; Park, Kyong Soo

    2015-07-01

    Bisphenol A (BPA) is a widely used endocrine disruptor. Recent epidemiologic results have suggested an association between exposure to BPA and cardiovascular disease, type 2 diabetes, and obesity. We investigated the in vivo effects of long-term oral exposure to BPA on insulin resistance and glucose intolerance. In the present study, 4- to 6-week-old male mice on a high-fat diet (HFD) were treated with 50 μg/kg body weight per day of BPA orally for 12 weeks. Long-term oral exposure to BPA along with an HFD for 12 weeks induced glucose intolerance in growing male mice. Intraperitoneal glucose tolerance tests showed that the mice that received an HFD and BPA exhibited a significantly larger area under the curve than did those that received an HFD only (119.9±16.8 vs. 97.9±18.2 mM/min, P=0.027). Body weight, percentage of white adipose tissue, and percentage of body fat did not differ between the two groups of mice. However, treatment with BPA reduced Akt phosphorylation at position Thr308 and GSK3β phosphorylation at position Ser9 in skeletal muscle. BPA tended to decrease serum adiponectin levels and to increase serum interleukin 6 and tumor necrosis factor α, although these findings were not statistically significant. Treatment with BPA did not induce any detrimental changes in the islet area or morphology or the insulin content of β cells. In conclusion, long-term oral exposure to BPA induced glucose intolerance and insulin resistance in growing mice. Decreased Akt phosphorylation in skeletal muscle by way of altered serum adipocytokine levels might be one mechanism by which BPA induces glucose intolerance. © 2015 Society for Endocrinology.

  4. Glucose intolerance and insulin resistance in cirrhosis are normalized after liver transplantation.

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    Merli, M; Leonetti, F; Riggio, O; Valeriano, V; Ribaudo, M C; Strati, F; Tisone, G; Casciani, C U; Capocaccia, L; Sprati, F

    1999-09-01

    Cirrhosis is often associated with insulin resistance and glucose intolerance. We evaluated if these alterations are restored by liver transplantation (LT). Glucose tolerance (oral glucose tolerance test [OGTT]), peripheral insulin sensitivity (euglycemic insulin clamp technique), glucose oxidation (indirect calorimetry), nonoxidative glucose disposal, and insulin secretion (hyperglycemic clamp technique) were measured in 6 patients (Group 1) before and 6 months after LT, in 12 patients (Group 2) who underwent LT 6 to 30 months previously, and in 6 healthy individuals (controls). In Group 1, glucose tolerance and insulin sensitivity (3.24 +/- 0.37 mg/kg/min) were normalized after LT (8.6 +/- 0.77 mg/kg/min; P <.0001; P = not significant vs. controls). The improved insulin-mediated glucose uptake was the result of a normalization of nonoxidative glucose disposal. Fasting insulin and C-peptide decreased from 24.6 +/- 3.3 microU/mL and 4.37 +/- 0.46 ng/dL, respectively, to 12.7 +/- 1.9 microU/mL and 2.46 +/- 0.5 ng/dL (controls: 10.0 +/- 3 microU/mL and 1.45 +/- 0.34 ng/dL). The glucose-induced increase of insulin concentration, which was higher before LT, showed a significant reduction, although the first phase of beta-cell secretion remained significantly higher compared with that of controls. All these findings were also confirmed in Group 2. The present data indicate that LT normalizes glucose tolerance and insulin sensitivity in cirrhotic patients through an improvement of both hepatic glucose clearance and the peripheral glucose disposal. The latter effect may be the result of the correction of chronic hyperinsulinemia. An increased first-phase beta-cell insulin secretion in response to high glucose levels persists, suggesting that a memory of previous insulin resistance is maintained.

  5. Alantolactone Improves Prolonged Exposure of Interleukin-6-Induced Skeletal Muscle Inflammation Associated Glucose Intolerance and Insulin Resistance

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    Minjee Kim

    2017-06-01

    Full Text Available The pro-inflammatory cytokine, Interleukin-6 (IL-6, has been proposed to be one of the mediators that link chronic inflammation to glucose intolerance and insulin resistance. Many studies have demonstrated the effects of IL-6 on insulin action in the skeletal muscle. However, few studies have investigated the effect of long-term treatment of IL-6, leading to glucose intolerance and insulin resistance. In the present study, we observed protective effects of alantolactone, a sesquiterpene lactone isolated from Inula helenium against glucose intolerance and insulin resistance induced by prolonged exposure of IL-6. Alantolactone has been reported to have anti-inflammatory and anti-cancer effects through IL-6-induced signal transducer and activator of transcription 3 (STAT3 signaling pathway. The relationship between IL-6 exposure and expression of toll-like receptor 4 (TLR4, involved in inflammation in the skeletal muscle, and the underlying mechanisms were investigated. We observed maximum dysregulation of glucose uptake after 40 ng/ml IL-6 induction for 24 h in L6 myotubes. Prolonged IL-6 exposure suppressed glucose uptake regulating alpha serine/threonine-protein kinase (AKT phosphorylation; however, pretreatment with alantolactone activated AKT phosphorylation and improved glucose uptake. Alantolactone also attenuated IL-6-stimulated STAT3 phosphorylation, followed by an increase in expression of negative regulator suppressor of cytokine signaling 3 (SOCS3. Furthermore, IL-6-induced expression of pathogen recognition receptor, TLR4, was also suppressed by alantolactone pretreatment. Post-silencing of STAT3 using siRNA approach, IL-6-stimulated siRNA-STAT3 improved glucose uptake and suppressed TLR4 gene expression. Taken together, we propose that, as a STAT3 inhibitor, alantolactone, improves glucose regulation in the skeletal muscle by inhibiting IL-6-induced STAT3-SOCS3 signaling followed by inhibition of the TLR4 gene expression. Therefore

  6. Early and rapid development of insulin resistance, islet dysfunction and glucose intolerance after high-fat feeding in mice overexpressing phosphodiesterase 3B

    DEFF Research Database (Denmark)

    Walz, Helena A; Härndahl, Linda; Wierup, Nils

    2006-01-01

    Inadequate islet adaptation to insulin resistance leads to glucose intolerance and type 2 diabetes. Here we investigate whether beta-cell cAMP is crucial for islet adaptation and prevention of glucose intolerance in mice. Mice with a beta-cell-specific, 2-fold overexpression of the c......AMP-degrading enzyme phosphodiesterase 3B (RIP-PDE3B/2 mice) were metabolically challenged with a high-fat diet. We found that RIP-PDE3B/2 mice early and rapidly develop glucose intolerance and insulin resistance, as compared with wild-type littermates, after 2 months of high-fat feeding. This was evident from....../2 mice. We conclude that accurate regulation of beta-cell cAMP is necessary for adequate islet adaptation to a perturbed metabolic environment and protective for the development of glucose intolerance and insulin resistance....

  7. Loss of Hepatic Mitochondrial Long-Chain Fatty Acid Oxidation Confers Resistance to Diet-Induced Obesity and Glucose Intolerance.

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    Lee, Jieun; Choi, Joseph; Selen Alpergin, Ebru S; Zhao, Liang; Hartung, Thomas; Scafidi, Susanna; Riddle, Ryan C; Wolfgang, Michael J

    2017-07-18

    The liver has a large capacity for mitochondrial fatty acid β-oxidation, which is critical for systemic metabolic adaptations such as gluconeogenesis and ketogenesis. To understand the role of hepatic fatty acid oxidation in response to a chronic high-fat diet (HFD), we generated mice with a liver-specific deficiency of mitochondrial long-chain fatty acid β-oxidation (Cpt2 L-/- mice). Paradoxically, Cpt2 L-/- mice were resistant to HFD-induced obesity and glucose intolerance with an absence of liver damage, although they exhibited serum dyslipidemia, hepatic oxidative stress, and systemic carnitine deficiency. Feeding an HFD induced hepatokines in mice, with a loss of hepatic fatty acid oxidation that enhanced systemic energy expenditure and suppressed adiposity. Additionally, the suppression in hepatic gluconeogenesis was sufficient to improve HFD-induced glucose intolerance. These data show that inhibiting hepatic fatty acid oxidation results in a systemic hormetic response that protects mice from HFD-induced obesity and glucose intolerance. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  8. Loss of Hepatic Mitochondrial Long-Chain Fatty Acid Oxidation Confers Resistance to Diet-Induced Obesity and Glucose Intolerance

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    Jieun Lee

    2017-07-01

    Full Text Available The liver has a large capacity for mitochondrial fatty acid β-oxidation, which is critical for systemic metabolic adaptations such as gluconeogenesis and ketogenesis. To understand the role of hepatic fatty acid oxidation in response to a chronic high-fat diet (HFD, we generated mice with a liver-specific deficiency of mitochondrial long-chain fatty acid β-oxidation (Cpt2L−/− mice. Paradoxically, Cpt2L−/− mice were resistant to HFD-induced obesity and glucose intolerance with an absence of liver damage, although they exhibited serum dyslipidemia, hepatic oxidative stress, and systemic carnitine deficiency. Feeding an HFD induced hepatokines in mice, with a loss of hepatic fatty acid oxidation that enhanced systemic energy expenditure and suppressed adiposity. Additionally, the suppression in hepatic gluconeogenesis was sufficient to improve HFD-induced glucose intolerance. These data show that inhibiting hepatic fatty acid oxidation results in a systemic hormetic response that protects mice from HFD-induced obesity and glucose intolerance.

  9. Indomethacin treatment prevents high fat diet-induced obesity and insulin resistance but not glucose intolerance in C57BL/6J Mice

    DEFF Research Database (Denmark)

    Fjære, Even; Aune, Ulrike Liisberg; Røen, Kristin

    2014-01-01

    a high fat/high sucrose (HF/HS) diet or a regular diet supplemented or not with indomethacin (±INDO) for 7 weeks. Development of obesity, insulin resistance, and glucose intolerance was monitored, and the effect of indomethacin on glucose-stimulated insulin secretion (GSIS) was measured in vivo...... and in vitro using MIN6 β-cells. We found that supplementation with indomethacin prevented HF/HS-induced obesity and diet-induced changes in systemic insulin sensitivity. Thus, HF/HS+INDO-fed mice remained insulin-sensitive. However, mice fed HF/HS+INDO exhibited pronounced glucose intolerance. Hepatic glucose...

  10. Overexpression of Rad in muscle worsens diet-induced insulin resistance and glucose intolerance and lowers plasma triglyceride level

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    Ilany, Jacob; Bilan, Philip J.; Kapur, Sonia; Caldwell, James S.; Patti, Mary-Elizabeth; Marette, Andre; Kahn, C. Ronald

    2006-03-01

    Rad is a low molecular weight GTPase that is overexpressed in skeletal muscle of some patients with type 2 diabetes mellitus and/or obesity. Overexpression of Rad in adipocytes and muscle cells in culture results in diminished insulin-stimulated glucose uptake. To further elucidate the potential role of Rad in vivo, we have generated transgenic (tg) mice that overexpress Rad in muscle using the muscle creatine kinase (MCK) promoter-enhancer. Rad tg mice have a 6- to 12-fold increase in Rad expression in muscle as compared to wild-type littermates. Rad tg mice grow normally and have normal glucose tolerance and insulin sensitivity, but have reduced plasma triglyceride levels. On a high-fat diet, Rad tg mice develop more severe glucose intolerance than the wild-type mice; this is due to increased insulin resistance in muscle, as exemplified by a rightward shift in the dose-response curve for insulin stimulated 2-deoxyglucose uptake. There is also a unexpected further reduction of the plasma triglyceride levels that is associated with increased levels of lipoprotein lipase in the Rad tg mice. These results demonstrate a potential synergistic interaction between increased expression of Rad and high-fat diet in creation of insulin resistance and altered lipid metabolism present in type 2 diabetes. diabetes mellitus | glucose transport | RGK GTPase | transgenic mouse

  11. Fat distribution and glucose intolerance among Greenland inuit

    DEFF Research Database (Denmark)

    Jørgensen, Marit Eika; Borch-Johnsen, Knut; Stolk, Ronald

    2013-01-01

    circumference [WC], and percentage of body fat) and the indices of glucose metabolism (fasting and 2-h glucose levels, insulin resistance per homeostasis model assessment [HOMA-IR], and the insulin sensitivity index [ISI0,120]) among Greenland Inuit. RESEARCH DESIGN AND METHODS A total of 3,108 adult Inuit...... associated with glucose intolerance, fasting and 2-h plasma glucose levels, HOMA-IR, and ISI0,120. VAT was more strongly associated with all outcomes than was SAT. After further adjustment for BMI or WC, VAT was associated with glucose intolerance and insulin resistance, whereas there was a trend toward...

  12. Pathogenesis of glucose intolerance in uremia.

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    DeFronzo, R A

    1978-12-01

    The pathogenesis of glucose intolerance in uremia was examined with the glucose clamp technique. Hyperglycemic clamp (n = 8): The plasma glucose concentration is acutely raised and maintained at 125 mg/dl above basal levels. Under these steady state conditions the glucose infusion rate, M, equals the amount of glucose metabolized: Predialysis M averaged 4.23 +/- 0.36 mg/kg/min and increased to 7.71 +/- 0.43 postdialysis (p less than 0.001). The plasma insulin response predialysis was 90 +/- 20 microU/ml and decreased to 80 +/- 23 microU/ml following dialysis. Consequently the M/l ratio, a measure of tissue sensitivity to insulin, increased by 80% +/- 25% (p less than 0.001) but still remained less than controls (p less than 0.01). Euglycemic insulin clamp (n = 10): The plasma insulin concentration is acutely raised by 100 microU/ml and the plasma glucose concentration is held constant at the basal level. Predialysis both M (3.37 +/- 0.36 mg/kg/min) and M/l (3.56 +/- 0.33 mg/kg/min per microU/ml X 100) were significantly less than controls (p less than 0.01). Postdialysis both M and M/l increased significantly (p less than 0.01) to a mean that was not significantly different from controls. Basal hepatic glucose production (n = 6), 2.15 +/- 0.09 mg/kg/min, was similar to controls and fell (87% +/- 4%) normally during the insulin clamp. In five uremic subjects in wom insulin binding to monocytes was measured, there was no correlation with tissue sensitivity to insulin (M/l). Significant abnormalities in both growth hormone and glucagon physiology were present in uremic individuals, but no correlation with either the presence or degree of glucose intolerance was demonstrable. In conclusion, glucose intolerance is universally present in uremic subjects and results primarily from peripheral tissue insensitivity to insulin. Insulin secretion is usually enhanced in an attempt to compensate for this insulin resistance but in occasional subjects uremia also inhibits beta

  13. The Usefulness of Homeostatic Measurement Assessment-Insulin Resistance (HOMA-IR) for Detection of Glucose Intolerance in Thai Women of Reproductive Age with Polycystic Ovary Syndrome.

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    Wongwananuruk, Thanyarat; Rattanachaiyanont, Manee; Leerasiri, Pichai; Indhavivadhana, Suchada; Techatraisak, Kitirat; Angsuwathana, Surasak; Tanmahasamut, Prasong; Dangrat, Chongdee

    2012-01-01

    Objectives. To study the cut-off point of Homeostatic Measurement Assessment-Insulin Resistance (HOMA-IR) as a screening test for detection of glucose intolerance in Thai women with polycystic ovary syndrome (PCOS). Study Design. Cross-sectional study. Setting. Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital. Subject. Two hundred and fifty Thai PCOS women who attended the Gynecologic Endocrinology Unit, during May 2007 to January 2009. Materials and Methods. The paitents were interviewed and examined for weight, height, waist circumference, and blood pressure. Venous blood samples were drawn twice, one at 12-hour fasting and the other at 2 hours after glucose loading. Results. The prevalence of glucose intolerance in Thai PCOS women was 20.0%. The mean of HOMA-IR was 3.53  ±  7.7. Area under an ROC curve for HOMA-IR for detecting glucose intolerance was 0.82. Using the cut-off value of HOMA-IR >2.0, there was sensitivity at 84.0%, specificity at 61.0%, positive predictive value at 35.0%, negative predictive value at 93.8%, and accuracy at 65.6%. Conclusion. HOMA-IR >2.0 was used for screening test for glucose intolerance in Thai PCOS women. If the result was positive, a specific test should be done to prove the diagnosis.

  14. Glucose effectiveness is a critical pathogenic factor leading to glucose intolerance and type 2 diabetes

    DEFF Research Database (Denmark)

    Alford, F. P.; Henriksen, J. E.; Rantzau, C.

    2018-01-01

    by mass action of glucose through the skeletal muscle membrane via facilitated Glut 4 transporters. However, GE is frequently forgotten as a significant contributor to the development of glucose intolerance in "at risk" individuals. Only limited studies have examined the role of a lower GE...... in such normoglycemic subjects with preexisting mild insulin resistance and β-cell dysfunction. These studies demonstrate that in "at risk" individuals, an initial low GE is a key contributor and predictor of future glucose intolerance, whereas an initial raised GE is protective against future glucose intolerance....... Conclusion: In "at risk" individuals, a low GE and genetically determined vulnerable β-cell function are more critical determinants of future glucose intolerance than their preexisting insulin-resistant state....

  15. Prevalence of insulin resistance and prediction of glucose intolerance and type 2 diabetes mellitus in women with polycystic ovary syndrome.

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    Vrbikova, Jana; Dvorakova, Katerina; Grimmichova, Tereza; Hill, Martin; Stanicka, Sona; Cibula, David; Bendlova, Bela; Starka, Luboslav; Vondra, Karel

    2007-01-01

    Diabetes mellitus type 2 (DM2) affects 10% of women with polycystic ovary syndrome (PCOS). We evaluated the sensitivity and specificity of clinical and fasting biochemical parameters in screening for impaired glucose tolerance (IGT) and DM2. Women with PCOS [n=244, age 27.4+/-7.5 years, body mass index (BMI) 27.5+/-6.9 kg/m(2)] and healthy women (n=57, age 26.8+/-5.8 years, BMI 21.3+/-2.1 kg/m(2)) underwent basal blood sampling and an oral glucose tolerance test (oGTT). Insulin resistance was identified in 40.2% of PCOS women. Impaired fasting glucose (5.6-6.9 mmol/L) was found in 30 subjects (12.3%), but the oGTT revealed IGT in only six of these cases and DM2 in one subject. IGT was found in 23 (9.4%) and DM2 in four (1.6%) of the women with PCOS. The conventional upper limits for total cholesterol, triglycerides, systolic and diastolic blood pressure and fasting glucose revealed low sensitivity for the identification of impaired glucose metabolism. No single parameter nor any combination of them showed an accuracy sufficient for screening of IGT or DM2 in PCOS patients. All PCOS patients should be screened using an oGTT to identify disturbances in glucose metabolism.

  16. Exenatide improves glucocorticoid-induced glucose intolerance in mice

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    Ruiying Zhao

    2011-01-01

    insulin resistance in these placebo-controlled experiments. Future clinical trials are justified to investigate the role of exenatide in the treatment of GC-induced glucose intolerance/diabetes.Keywords: exenatide, dexamethasone, glucocorticoid, insulin resistance, mouse model

  17. Early and rapid development of insulin resistance, islet dysfunction and glucose intolerance after high-fat feeding in mice overexpressing phosphodiesterase 3B

    DEFF Research Database (Denmark)

    Walz, Helena A; Härndahl, Linda; Wierup, Nils

    2006-01-01

    advanced fasting hyperinsulinemia and early development of hyper-glycemia, in spite of hyperinsulinemia, as well as impaired capacity of insulin to suppress plasma glucose in an insulin tolerance test. In vitro analyses of insulin-stimulated lipogenesis in adipocytes and glucose uptake in skeletal muscle......AMP-degrading enzyme phosphodiesterase 3B (RIP-PDE3B/2 mice) were metabolically challenged with a high-fat diet. We found that RIP-PDE3B/2 mice early and rapidly develop glucose intolerance and insulin resistance, as compared with wild-type littermates, after 2 months of high-fat feeding. This was evident from...... perturbations, such as centrally located alpha-cells and reduced immunostaining for insulin and GLUT2 in islets from RIP-PDE3B/2 mice. Additionally, in vitro experiments revealed that the insulin secretory response to glucagon-like peptide-1 stimulation was markedly reduced in islets from high-fat-fed RIP-PDE3B...

  18. Continued glucose output after re-feeding contributes to glucose intolerance in hyperthyroidism.

    OpenAIRE

    Holness, M J; Sugden, M C

    1987-01-01

    The effects of hyperthyroidism to elicit glucose intolerance after glucose administration were decreased under conditions where hepatic glucose output was suppressed. It is concluded that continued hepatic glucose output contributes to abnormal glucose tolerance in hyperthyroidism.

  19. Mice Deficient in Proglucagon-Derived Peptides Exhibit Glucose Intolerance on a High-Fat Diet but Are Resistant to Obesity.

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    Yusuke Takagi

    Full Text Available Homozygous glucagon-GFP knock-in mice (Gcggfp/gfp lack proglucagon derived-peptides including glucagon and GLP-1, and are normoglycemic. We have previously shown that Gcggfp/gfp show improved glucose tolerance with enhanced insulin secretion. Here, we studied glucose and energy metabolism in Gcggfp/gfp mice fed a high-fat diet (HFD. Male Gcggfp/gfp and Gcggfp/+ mice were fed either a normal chow diet (NCD or an HFD for 15-20 weeks. Regardless of the genotype, mice on an HFD showed glucose intolerance, and Gcggfp/gfp mice on HFD exhibited impaired insulin secretion whereas Gcggfp/+ mice on HFD exhibited increased insulin secretion. A compensatory increase in β-cell mass was observed in Gcggfp/+mice on HFD, but not in Gcggfp/gfp mice on the same diet. Weight gain was significantly lower in Gcggfp/gfp mice than in Gcggfp/+mice. Oxygen consumption was enhanced in Gcggfp/gfp mice compared to Gcggfp/+ mice on an HFD. HFD feeding significantly increased uncoupling protein 1 mRNA expression in brown adipose and inguinal white adipose tissues of Gcggfp/gfp mice, but not of Gcggfp/+mice. Treatment with the glucagon-like peptide-1 receptor agonist liraglutide (200 mg/kg improved glucose tolerance in Gcggfp/gfp mice and insulin content in Gcggfp/gfp and Gcggfp/+ mice was similar after liraglutide treatment. Our findings demonstrate that Gcggfp/gfp mice develop diabetes upon HFD-feeding in the absence of proglucagon-derived peptides, although they are resistant to diet-induced obesity.

  20. Glucose intolerance among apparently healthy Hausa-Fulani ...

    African Journals Online (AJOL)

    Background: Glucose intolerance has been recently reclassified by the World Health Organization (WHO) incorporating a new class known as impaired fasting glycaemia. Previous studies in this environment looked as diabetes mellitus only but not the other forms of glucose intolerance. Objectives: To study the prevalence ...

  1. Random plasma glucose in serendipitous screening for glucose intolerance: screening for impaired glucose tolerance study 2.

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    Ziemer, David C; Kolm, Paul; Foster, Jovonne K; Weintraub, William S; Vaccarino, Viola; Rhee, Mary K; Varughese, Rincy M; Tsui, Circe W; Koch, David D; Twombly, Jennifer G; Narayan, K M Venkat; Phillips, Lawrence S

    2008-05-01

    With positive results from diabetes prevention studies, there is interest in convenient ways to incorporate screening for glucose intolerance into routine care and to limit the need for fasting diagnostic tests. The aim of this study is to determine whether random plasma glucose (RPG) could be used to screen for glucose intolerance. This is a cross-sectional study. The participants of this study include a voluntary sample of 990 adults not known to have diabetes. RPG was measured, and each subject had a 75-g oral glucose tolerance test several weeks later. Glucose intolerance targets included diabetes, impaired glucose tolerance (IGT), and impaired fasting glucose(110) (IFG(110); fasting glucose, 110-125 mg/dl, and 2 h glucose RPG to identify diabetes and 0.72 (0.68-0.75) to identify any glucose intolerance, both highly significant (p RPG values should be considered by health care providers to be an opportunistic initial screening test and used to prompt further evaluation of patients at risk of glucose intolerance. Such "serendipitous screening" could help to identify unrecognized diabetes and prediabetes.

  2. The effective fraction isolated from Radix Astragali alleviates glucose intolerance, insulin resistance and hypertriglyceridemia in db/db diabetic mice through its anti-inflammatory activity.

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    Hoo, Ruby Lc; Wong, Janice Yl; Qiao, Cf; Xu, A; Xu, Hx; Lam, Karen Sl

    2010-08-24

    Macrophage infiltration in adipose tissue together with the aberrant production of pro-inflammatory cytokines has been identified as the key link between obesity and its related metabolic disorders. This study aims to isolate bioactive ingredients from the traditional Chinese herb Radix Astragali (Huangqi) that alleviate obesity-induced metabolic damage through inhibiting inflammation. Active fraction (Rx) that inhibits pro-inflammatory cytokine production was identified from Radix Astragali by repeated bioactivity-guided high-throughput screening. Major constituents in Rx were identified by column chromatography followed by high-performance liquid chromatography (HPLC) and mass-spectrometry. Anti-diabetic activity of Rx was evaluated in db/db mice. Treatment with Rx, which included calycosin-7-β-D-glucoside (0.9%), ononin (1.2%), calycosin (4.53%) and formononetin (1.1%), significantly reduced the secretion of pro-inflammatory cytokines (TNF-α, IL-6 and MCP-1) in human THP-1 macrophages and lipopolysaccharide (LPS)-induced activation of NF-κB in mouse RAW-Blue macrophages in a dose-dependent manner. Chronic administration of Rx in db/db obese mice markedly decreased the levels of both fed and fasting glucose, reduced serum triglyceride, and also alleviated insulin resistance and glucose intolerance when compared to vehicle-treated controls. The mRNA expression levels of inflammatory cell markers CD68 and F4/80, and cytokines MCP-1, TNF-α and IL-6 were significantly reduced in epididymal adipose tissue while the alternatively activated macrophage marker arginase I was markedly increased in the Rx-treated mice. These findings suggest that suppression of the inflammation pathways in macrophages represents a valid strategy for high-throughput screening of lead compounds with anti-diabetic and insulin sensitizing properties, and further support the etiological role of inflammation in the pathogenesis of obesity-related metabolic disorders.

  3. The effective fraction isolated from Radix Astragali alleviates glucose intolerance, insulin resistance and hypertriglyceridemia in db/db diabetic mice through its anti-inflammatory activity

    Directory of Open Access Journals (Sweden)

    Hoo Ruby LC

    2010-08-01

    Full Text Available Abstract Background Macrophage infiltration in adipose tissue together with the aberrant production of pro-inflammatory cytokines has been identified as the key link between obesity and its related metabolic disorders. This study aims to isolate bioactive ingredients from the traditional Chinese herb Radix Astragali (Huangqi that alleviate obesity-induced metabolic damage through inhibiting inflammation. Methods Active fraction (Rx that inhibits pro-inflammatory cytokine production was identified from Radix Astragali by repeated bioactivity-guided high-throughput screening. Major constituents in Rx were identified by column chromatography followed by high-performance liquid chromatography (HPLC and mass-spectrometry. Anti-diabetic activity of Rx was evaluated in db/db mice. Results Treatment with Rx, which included calycosin-7-β-D-glucoside (0.9%, ononin (1.2%, calycosin (4.53% and formononetin (1.1%, significantly reduced the secretion of pro-inflammatory cytokines (TNF-α, IL-6 and MCP-1 in human THP-1 macrophages and lipopolysaccharide (LPS-induced activation of NF-κB in mouse RAW-Blue macrophages in a dose-dependent manner. Chronic administration of Rx in db/db obese mice markedly decreased the levels of both fed and fasting glucose, reduced serum triglyceride, and also alleviated insulin resistance and glucose intolerance when compared to vehicle-treated controls. The mRNA expression levels of inflammatory cell markers CD68 and F4/80, and cytokines MCP-1, TNF-α and IL-6 were significantly reduced in epididymal adipose tissue while the alternatively activated macrophage marker arginase I was markedly increased in the Rx-treated mice. Conclusion These findings suggest that suppression of the inflammation pathways in macrophages represents a valid strategy for high-throughput screening of lead compounds with anti-diabetic and insulin sensitizing properties, and further support the etiological role of inflammation in the pathogenesis of

  4. Association of Androgen Excess with Glucose Intolerance in Women with Polycystic Ovary Syndrome

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    Zhang, Bingjie; Wang, Jing; Shen, Shanmei; Liu, Jiayi; Sun, Jie; Ye, Xiao

    2018-01-01

    Women with polycystic ovary syndrome (PCOS) show high prevalence of glucose intolerance. This study aimed to investigate the association of androgen excess with glucose intolerance in PCOS. A total of 378 women with PCOS participated in the study. Free androgen index (FAI) was selected as indicator of hyperandrogenism. Insulin sensitivity was assessed by 1/homeostasis model assessment of insulin resistance (1/HOMA-IR) and Matsuda insulin sensitivity index (ISIM); β-cell function was assessed by disposition index (DI). We found that women with glucose intolerance had higher FAI levels compared to women with normal glucose tolerance (NGT) (prediabetes 6.2, T2DM 7.9 versus NGT 5.0, resp.; p intolerance (OR = 2.480, 95% CI 1.387–4.434), even after adjusting for age, BMI, waist circumference, hypertension, fasting insulin, testosterone, SHBG, and family history of diabetes. In addition, with FAI increase, glycosylated hemoglobin (HbA1c), plasma glucose concentrations, and serum insulin levels increased, while insulin sensitivity and β-cell function decreased. Our results suggested that androgen excess indicated by high FAI levels might serve as indicator of glucose intolerance, as it might promote insulin resistance and β-cell dysfunction in women with PCOS.

  5. Glucose effectiveness is a critical pathogenic factor leading to glucose intolerance and type 2 diabetes: An ignored hypothesis.

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    Alford, F P; Henriksen, J E; Rantzau, C; Beck-Nielsen, H

    2018-02-16

    Although the ability of glucose to mediate its own in vivo metabolism is long documented, the quantitative measurement of whole body glucose-mediated glucose disposal at basal insulin levels (glucose effectiveness [GE]), followed the introduction of the Minimal Model intravenous glucose tolerance test technique. A literature review, combined with our own studies, of the role of GE in glucose metabolism in normal and "at risk" individuals, was undertaken to determine GE's contribution to glucose homeostasis. GE accounts for ~45% to 65% of glucose disposal in man. A negative association between GE and insulin meditated glucose disposal (Si), is present in normal subjects without a family history of type 2 diabetes mellitus but is absent in normoglycaemic "at risk" relatives with a positive family history of diabetes mellitus. Intracellular GE disposal is mediated by mass action of glucose through the skeletal muscle membrane via facilitated Glut 4 transporters. However, GE is frequently forgotten as a significant contributor to the development of glucose intolerance in "at risk" individuals. Only limited studies have examined the role of a lower GE in such normoglycemic subjects with preexisting mild insulin resistance and β-cell dysfunction. These studies demonstrate that in "at risk" individuals, an initial low GE is a key contributor and predictor of future glucose intolerance, whereas an initial raised GE is protective against future glucose intolerance. In "at risk" individuals, a low GE and genetically determined vulnerable β-cell function are more critical determinants of future glucose intolerance than their preexisting insulin-resistant state. Copyright © 2018 John Wiley & Sons, Ltd.

  6. Remedies for glucose intolerance – are traditional herbal ...

    African Journals Online (AJOL)

    Background:Preventing or delaying the onset of diabetes in prediabetes has the potential to reduce the disease prevalence. Objective:The effectiveness of traditional herbal concoctions for diabetes in ameliorating glucose intolerance was investigated. Material and Methods:Oral glucose tolerance test (OGTT) was carried ...

  7. The prevalence of glucose intolerance among antenatal clients at ...

    African Journals Online (AJOL)

    Objectives: To determine the prevalence of and associated factors for glucose intolerance among antenatal clients at Kenyatta National Hospital at 24-36 weeks of gestation. Design: Cross-sectional analytical study. Setting: Kenyatta National Hospital antenatal clinic. Subjects: One hundred and two (102) antenatal mothers ...

  8. Glucose intolerance in a xenotransplantation model

    DEFF Research Database (Denmark)

    Dahl, Kirsten; Buschard, Karsten; Gram, Dorte X.

    2006-01-01

    Xenotransplantation holds the promise of replacing failing human organs with organs of animal origin. Transplantation of pancreatic islets from pigs to humans might restore glucose homeostasis and offer diabetic patients considerable improvement in their quality of life. The alpha-gal epitope......-galactosyl transferase knockout mice (alpha-GT KO) develop cataract, but no other lesions have been established in these mice. Here we report for the first time that alpha-GT KO mice have impaired glucose tolerance (p

  9. Perceived psychosocial stress and glucose intolerance among pregnant Hispanic women.

    Science.gov (United States)

    Silveira, M L; Whitcomb, B W; Pekow, P; Braun, B; Markenson, G; Dole, N; Manson, J E; Solomon, C G; Carbone, E T; Chasan-Taber, L

    2014-12-01

    Prior literature suggests a positive association between psychosocial stress and the risk of diabetes in non-pregnant populations, but studies during pregnancy are sparse. We evaluated the relationship between stress and glucose intolerance among 1115 Hispanic (predominantly Puerto Rican) prenatal care patients in Proyecto Buena Salud, a prospective cohort study in Western Massachusetts (2006-2011). Cohen's Perceived Stress Scale (PSS-14) was administered in early (mean = 12.3 weeks gestation; range 4.1-18 weeks) and mid- (mean = 21.3 weeks gestation; range 18.1-26 weeks) pregnancy. Participants were classified as having a pregnancy complicated by gestational diabetes mellitus, impaired glucose tolerance, and abnormal glucose tolerance, based on the degree of abnormality on glucose tolerance testing between 24 and 28 weeks of gestation. The prevalence of gestational diabetes mellitus, impaired glucose tolerance, and abnormal glucose tolerance was 4.1%, 7.2%, and 14.5%, respectively. Absolute levels of early or mid-pregnancy stress were not significantly associated with glucose intolerance. However, participants with an increase in stress from early to mid-pregnancy had a 2.6-fold increased odds of gestational diabetes mellitus (95% confidence intervals: 1.0-6.9) as compared to those with no change or a decrease in stress after adjusting for age and pre-pregnancy body mass index. In addition, every one-point increase in stress scores was associated with a 5.5mg/dL increase in screening glucose level (β=5.5; standard deviation=2.8; P=0.05), after adjusting for the same variables. In this population of predominantly Puerto Rican women, stress patterns during pregnancy may influence the risk of glucose intolerance. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  10. Glucose intolerance in a xenotransplantation model

    DEFF Research Database (Denmark)

    Dahl, Kirsten; Buschard, Karsten; Gram, Dorte X.

    2006-01-01

    Xenotransplantation holds the promise of replacing failing human organs with organs of animal origin. Transplantation of pancreatic islets from pigs to humans might restore glucose homeostasis and offer diabetic patients considerable improvement in their quality of life. The alpha-gal epitope, pr...

  11. Selective breeding of mice for different susceptibilities to high fat diet‐induced glucose intolerance: Development of two novel mouse lines, Selectively bred Diet‐induced Glucose intolerance‐Prone and ‐Resistant

    OpenAIRE

    Nagao, Mototsugu; Asai, Akira; Kawahara, Momoyo; Nakajima, Yasushi; Sato, Yuki; Tanimura, Kyoko; Okajima, Fumitaka; Takaya, Makiyo; Sudo, Mariko; Takemitsu, Shuji; Harada, Taro; Sugihara, Hitoshi; Oikawa, Shinichi

    2011-01-01

    Abstract Aims/Introduction:  The development of type 2 diabetes is primarily due to lifestyle and environmental factors, as well as genetics, as shown by familial clustering. To establish mouse lines for evaluating heritable factors determining susceptibility to diet‐induced diabetes, we performed selective breeding for differences in high fat diet (HFD)‐induced glucose intolerance. Materials and Methods:  Selective breeding was performed using hybrid mice of C57BL/6J, C3H/HeJ and AKR/N backg...

  12. Dietary patterns in Greenland and their relationship with type 2 diabetes mellitus and glucose intolerance.

    Science.gov (United States)

    Jeppesen, Charlotte; Bjerregaard, Peter; Jørgensen, Marit E

    2014-02-01

    Traditional Inuit dietary patterns have been found to be beneficial for CVD but have not been investigated in relation to glucose intolerance. We examined the association between dietary patterns and type 2 diabetes mellitus (T2DM), impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). Cross-sectional design with a priori derived dietary patterns from an FFQ resulted in five patterns: imported meat (n 196), traditional food (n 601), balanced diet (n 126), unhealthy diet (n 652) and standard diet (n 799). Associations between dietary patterns and glucose-related outcomes were tested by linear and logistic regression analyses. Data included: dietary intake by FFQ, waist circumference, ethnicity, frequency of alcohol intake and smoking, physical activity, and oral glucose tolerance test results. Fasting participants and those without diagnosed T2DM were classified into normal glucose tolerance, IGT, IFG or T2DM. HOMA-IR (homeostatic model assessment-insulin resistance index) and HOMA-β (homeostatic model assessment of β-cell function) were calculated. Data included 2374 Inuit, aged 18+ years. Participants with a traditional dietary pattern had higher fasting plasma glucose (mean 5·73 (95% CI 5·68, 5·78) mmol/l, P food was positively associated with T2DM, IFG and fasting plasma glucose, and negatively associated with β-cell function, compared with a standard diet. The imported meat diet seemed the best in relation to glucose intolerance, with lowest fasting plasma glucose and lowest odds for IFG and T2DM.

  13. Artificial sweeteners induce glucose intolerance by altering the gut microbiota.

    Science.gov (United States)

    Suez, Jotham; Korem, Tal; Zeevi, David; Zilberman-Schapira, Gili; Thaiss, Christoph A; Maza, Ori; Israeli, David; Zmora, Niv; Gilad, Shlomit; Weinberger, Adina; Kuperman, Yael; Harmelin, Alon; Kolodkin-Gal, Ilana; Shapiro, Hagit; Halpern, Zamir; Segal, Eran; Elinav, Eran

    2014-10-09

    Non-caloric artificial sweeteners (NAS) are among the most widely used food additives worldwide, regularly consumed by lean and obese individuals alike. NAS consumption is considered safe and beneficial owing to their low caloric content, yet supporting scientific data remain sparse and controversial. Here we demonstrate that consumption of commonly used NAS formulations drives the development of glucose intolerance through induction of compositional and functional alterations to the intestinal microbiota. These NAS-mediated deleterious metabolic effects are abrogated by antibiotic treatment, and are fully transferrable to germ-free mice upon faecal transplantation of microbiota configurations from NAS-consuming mice, or of microbiota anaerobically incubated in the presence of NAS. We identify NAS-altered microbial metabolic pathways that are linked to host susceptibility to metabolic disease, and demonstrate similar NAS-induced dysbiosis and glucose intolerance in healthy human subjects. Collectively, our results link NAS consumption, dysbiosis and metabolic abnormalities, thereby calling for a reassessment of massive NAS usage.

  14. Predicting glucose intolerance with normal fasting plasma glucose by the components of the metabolic syndrome

    International Nuclear Information System (INIS)

    Pei, D.; Lin, J.; Kuo, S.; Wu, D.; Li, J.; Hsieh, C.; Wu, C.; Hung, Y.; Kuo, K.

    2007-01-01

    Surprisingly it is estimated that about half of type 2 diabetics remain undetected. The possible causes may be partly attributable to people with normal fasting plasma glucose (FPG) but abnormal postprandial hyperglycemia. We attempted to develop an effective predictive model by using the metabolic syndrome (MeS) components as parameters to identify such persons. All participants received a standard 75 gm oral glucose tolerance test which showed that 106 had normal glucose tolerance, 61 had impaired glucose tolerance and 6 had diabetes on isolated postchallenge hyperglycemia. We tested five models which included various MeS components. Model 0: FPG; Model 1 (Clinical history model): family history (FH), FPG, age and sex; Model 2 (MeS model): Model 1 plus triglycerides, high-density lipoprotein cholesterol, body mass index, systolic blood pressure and diastolic blood pressure; Model 3: Model 2 plus fasting plasma insulin (FPI); Model 4: Model 3 plus homeostasis model assessment of insulin resistance. A receiver-operating characteristic (ROC) curve was used to determine the predictive discrimination of these models. The area under the ROC curve of the Model 0 was significantly larger than the area under the diagonal reference line. All the other 4 models had a larger area under the ROC curve than Model 0. Considering the simplicity and lower cost of Model 2, it would be the best model to use. Nevertheless, Model 3 had the largest area under the ROC curve. We demonstrated that Model 2 and 3 have a significantly better predictive discrimination to identify persons with normal FPG at high risk for glucose intolerance. (author)

  15. Coffee Consumption Attenuates Insulin Resistance and Glucose ...

    African Journals Online (AJOL)

    Coffee Consumption Attenuates Insulin Resistance and Glucose Intolerance in Rats fed on High-Sucrose Diet. ... Summary: Several epidemiological evidences indicate that consumption of coffee is associated with a lower risk of type 2 diabetes mellitus (T2DM) however; there is dearth of experimental data to support these ...

  16. Coffee Consumption Attenuates Insulin Resistance and Glucose ...

    African Journals Online (AJOL)

    olayemitoyin

    J. Physiol. Sci. 28(December 2013) 179–185 www.njps.com.ng. Coffee Consumption Attenuates Insulin Resistance and Glucose. Intolerance in Rats fed on High-Sucrose Diet. Morakinyo AO*, Adekunbi DA, Dada KA and Adegoke OA. Department of Physiology, College of Medicine of the University of Lagos, Lagos. Nigeria.

  17. Sox9-haploinsufficiency causes glucose intolerance in mice.

    Directory of Open Access Journals (Sweden)

    Claire L Dubois

    Full Text Available The HMG box transcription factor Sox9 plays a critical role in progenitor cell expansion during pancreas organogenesis and is required for proper endocrine cell development in the embryo. Based on in vitro studies it has been suggested that Sox9 controls expression of a network of important developmental regulators, including Tcf2/MODY5, Hnf6, and Foxa2, in pancreatic progenitor cells. Here, we sought to: 1 determine whether Sox9 regulates this transcriptional network in vivo and 2 investigate whether reduced Sox9 gene dosage leads to impaired glucose homeostasis in adult mice. Employing two genetic models of temporally-controlled Sox9 inactivation in pancreatic progenitor cells, we demonstrate that contrary to in vitro findings, Sox9 is not required for Tcf2, Hnf6, or Foxa2 expression in vivo. Moreover, our analysis revealed a novel role for Sox9 in maintaining the expression of Pdx1/MODY4, which is an important transcriptional regulator of beta-cell development. We further show that reduced beta-cell mass in Sox9-haploinsufficient mice leads to glucose intolerance during adulthood. Sox9-haploinsufficient mice displayed 50% reduced beta-cell mass at birth, which recovered partially via a compensatory increase in beta-cell proliferation early postnatally. Endocrine islets from mice with reduced Sox9 gene dosage exhibited normal glucose stimulated insulin secretion. Our findings show Sox9 plays an important role in endocrine development by maintaining Ngn3 and Pdx1 expression. Glucose intolerance in Sox9-haploinsufficient mice suggests that mutations in Sox9 could play a role in diabetes in humans.

  18. First Trimester Maternal Glycated Hemoglobin and Sex Hormone-Binding Globulin Do Not Predict Third Trimester Glucose Intolerance of Pregnancy.

    Science.gov (United States)

    Berggren, Erica K; Boggess, Kim A; Mathew, Leny; Culhane, Jennifer

    2017-04-01

    Early pregnancy prediction of third trimester glucose intolerance may identify a population of women whose trajectory toward gestational diabetes mellitus (GDM) is modifiable. We assessed whether first trimester glycated hemoglobin (HbA1c) and sex hormone-binding globulin (SHBG), markers of insulin resistance, predicted third trimester glucose intolerance. Nondiabetic women with singleton pregnancies enrolled in a prospective observational study, 11 0/7 to 14 6/7 weeks. At enrollment, maternal characteristics, medical history, and blood samples were collected for HbA1c and SHBG. Two-step GDM screening was performed, 22 0/7 to 33 6/7 weeks. A 50 g oral glucose tolerance test ≥130 mg/dL defined screen positive, or glucose intolerance. Carpenter-Coustan criteria diagnosed GDM. Means HbA1c and SHBG were compared between glucose-intolerant versus normoglycemic women, and GDM versus no GDM women. We report unadjusted and adjusted odds ratios (OR; 95% confidence interval [CI]) of regression analyses. Adjusted models include race, enrollment body mass index, and history of GDM. Among 250 women, 29% were glucose intolerant and 6% had GDM. Among glucose-intolerant women, HbA1c was higher (5.3 ± 0.3 vs. 5.1 ± 0.3, P = .01) and associated with glucose intolerance in unadjusted, but not adjusted, models (OR: 2.9, 95% CI: 1.2-7.1; adjusted odds ratio [aOR]: 2.0, 95% CI: 0.7-5.4). Among GDM women, HbA1c was higher (5.4 ± 0.4 vs 5.2 ± 0.3, P = .002) and SHBG was lower (228 ± 72 vs 288 ± 93 mmol/L, P = .02). The HbA1c predicted GDM in unadjusted (OR: 13.2, 95% CI: 2.6-68.0) but not adjusted (aOR: 6.7, 95% CI: 0.8-55.2) models. Although metabolic alterations may well precede third trimester glucose intolerance, neither HbA1c of SHBG remained an independent predictor of glucose intolerance or GDM in adjusted models.

  19. Glucan-rich polysaccharides from Pleurotus sajor-caju (Fr.) Singer prevents glucose intolerance, insulin resistance and inflammation in C57BL/6J mice fed a high-fat diet.

    Science.gov (United States)

    Kanagasabapathy, Gowri; Kuppusamy, Umah Rani; Abd Malek, Sri Nurestri; Abdulla, Mahmood Ameen; Chua, Kek-Heng; Sabaratnam, Vikineswary

    2012-12-21

    Pleurotus sajor-caju (P. sajor-caju) has been extremely useful in the prevention of diabetes mellitus due to its low fat and high soluble fiber content for thousands of years. Insulin resistance is a key component in the development of diabetes mellitus which is caused by inflammation. In this study, we aimed to investigate the in vivo efficacy of glucan-rich polysaccharide of P. sajor-caju (GE) against diabetes mellitus and inflammation in C57BL/6J mice fed a high-fat diet. Diabetes was induced in C57BL/6J mice by feeding a high-fat diet. The mice were randomly assigned to 7 groups (n=6 per group). The control groups in this study were ND (for normal diet) and HFD (for high-fat diet). The treated groups were ND240 (for normal diet) (240 mg/kg b.w) and HFD60, HFD120 and HFD240 (for high-fat), where the mice were administrated with three dosages of GE (60, 120, 240 mg GE/kg b.w respectively). Metformin (2 mg/kg b.w) served as positive control. The glucose tolerance test, glucose and insulin levels were measured at the end of 16 weeks. Expressions of genes for inflammatory markers, GLUT-4 and adiponectin in the adipose tissue of the mice were assessed. One-way ANOVA and Duncan's multiple range tests (DMRT) were used to determine the significant differences between groups. GE treated groups improved the glucose tolerance, attenuated hyperglycemia and hyperinsulinemia in the mice by up-regulating the adiponectin and GLUT-4 gene expressions. The mice in GE treated groups did not develop insulin resistance. GE also down-regulated the expression of inflammatory markers (IL-6, TNF-α, SAA2, CRP and MCP-1) via attenuation of nuclear transcription factors (NF-κB). Glucan-rich polysaccharide of P. sajor-caju can serve as a potential agent for prevention of glucose intolerance, insulin resistance and inflammation.

  20. Association between whole blood mercury and glucose intolerance among adult Inuit in Greenland.

    Science.gov (United States)

    Jeppesen, Charlotte; Valera, Beatriz; Nielsen, Nina O; Bjerregaard, Peter; Jørgensen, Marit E

    2015-11-01

    The Arctic diet is partly constituted by traditional food characterized by top predator animals such as whales, walrus, and seals with high mercury content. Mercury exposure has been associated with glucose intolerance in Western populations. We studied the association between whole blood mercury and glucose intolerance in a highly exposed non-Western population Cross-sectional study of 2640 Inuit (18+ years) with information on ancestry, smoking, waist circumference, total energy intake, and physical activity. Mercury, fasting- and 2-h plasma glucose, insulin, and c-peptide were measured in blood. Fasting participants without diabetes were classified into normal glucose tolerance, impaired glucose tolerance, impaired fasting glycemia, or type 2 diabetes. We calculated hepatic insulin resistance with homoeostatic model assessment - insulin resistance index, peripheral insulin sensitivity by ISI0,120., and relative beta cell function by c-peptide/insulin ratio. We conducted adjusted linear- and logistic regression analyses. For an increase in whole blood mercury of 5 µg/L we found a positive association with fasting glucose [% change=0.25 (95% CI: 0.20; 0.30); p<0.001], and 2-h glucose [% change=0.23 (95% CI: 0.05; 0.40); p=0.01]. Mercury was weakly associated with impaired fasting glycemia [OR=1.03 (95% CI: 1.02; 1.05)], and type 2 diabetes [OR=1.02 (95% CI: 1.01; 1.04)]. While the study found a weak but statistically significant association between whole blood mercury and both impaired fasting glycemia and type 2 diabetes, no associations were found with measures of underlying disturbances in glucose homoeostasis. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Vitamin E and Vitamin C supplementation does not prevent glucose intolerance in obese-prone rats

    Science.gov (United States)

    Obesity-induced glucose intolerance affects over 70 million Americans. Elevated oxidative stress is associated with development of glucose intolerance. In this work, we tested the hypothesis that supplementation with the anti-oxidants vitamin E (d-alpha-tocopherol acetate; 0.4 g/kg diet) and vitamin...

  2. Perinatal significance of diagnosing glucose intolerance during pregnancy with portable glucose meter.

    Science.gov (United States)

    Jakobi, Peter; Weissman, Amir; Egozi, Judith; Minuchin, Oscar; Geva, Adam

    2003-01-01

    To evaluate the effect on perinatal outcome of replacing glucose measurements for the diagnosis of gestational diabetes mellitus in central laboratories with those obtained by portable glucose meter. Simultaneously, venous blood samples were taken at the 100-g glucose tolerance test, and finger capillary blood glucose levels were also measured with a portable glucose meter in 180 pregnant patients. Patient management was according to the venous plasma glucose results. Following deliveries, the women were reallocated to diagnostic groups by both methods of measurements and by using the same cutoff values, and the outcome data were compared. By using glucose values obtained by portable glucose meters instead of the results attained in the central laboratory, more women were diagnosed with gestational diabetes (33 vs 25) and the perinatal outcome was comparable. Obstetricians have to identify glucose intolerance during pregnancy in order to prevent macrosomia and its perinatal complications. These goals can be achieved with at least the same efficacy by performing the 100-g glucose tolerance test with a portable glucose meter as with current laboratory methods. Such an approach is time and resource saving and more convenient for both patients and health providers.

  3. Glucose Intolerance after a Recent History of Gestational Diabetes Based on the 2013 WHO Criteria.

    Science.gov (United States)

    Benhalima, Katrien; Jegers, Katleen; Devlieger, Roland; Verhaeghe, Johan; Mathieu, Chantal

    2016-01-01

    Uncertainty exists on the prevalence of glucose intolerance in women with a recent diagnosis of gestational diabetes (GDM) based on a two-step screening strategy and the 2013 World Health Organization (WHO) criteria. Our aim was to evaluate the uptake of postpartum screening, the prevalence and the risk factors for glucose intolerance in women with a recent history of GDM. Retrospective analysis of the medical records of women with a recent history of GDM diagnosed in a universal two-step screening strategy with the 2013 WHO criteria. All women with a history of GDM are advised to undergo a 75g oral glucose tolerance test (OGTT) around 12 weeks postpartum. Indices of insulin sensitivity (the Matsuda index and the reciprocal of the homeostasis model assessment of insulin resistance, 1/HOMA-IR) and an index of beta-cell function, the Insulin Secretion-Sensitivity Index-2 (ISSI-2) were calculated based on the OGTT postpartum. Multivariable logistic regression was used to adjust for confounders such as age, BMI, ethnicity and breastfeeding. Of the 191 women with GDM, 29.3% (56) did not attend the scheduled postpartum OGTT. These women had a higher BMI (28.6 ±6.8 vs. 26.2 ± 5.6, p = 0.015), were more often from an ethnic minority (EM) background (41.1% vs. 25.2%, p = 0.029) and smoked more often during pregnancy (14.3% vs. 2.2%, p = 0.001) than women who attended the OGTT postpartum. Of all women (135) who received an OGTT postpartum, 42.2% (57) had prediabetes (11.9% impaired fasting glucose, 24.4% impaired glucose tolerance and 5.9% both impaired fasting and impaired glucose tolerance) and 1.5% (2) had overt diabetes. Compared to women with a normal OGTT postpartum, women with glucose intolerance were older (32.5±4.3 vs. 30.8±4.8 years, p = 0.049), were more often obese (34.5% vs. 17.3%, p = 0.023), were more often from an EM background (33.9% vs. 18.4%, p = 0.040), less often breastfed (69.5% vs. 84.2%, p = 0.041) and had more often an abnormal fasting glycaemia

  4. Glucose Intolerance after a Recent History of Gestational Diabetes Based on the 2013 WHO Criteria.

    Directory of Open Access Journals (Sweden)

    Katrien Benhalima

    Full Text Available Uncertainty exists on the prevalence of glucose intolerance in women with a recent diagnosis of gestational diabetes (GDM based on a two-step screening strategy and the 2013 World Health Organization (WHO criteria. Our aim was to evaluate the uptake of postpartum screening, the prevalence and the risk factors for glucose intolerance in women with a recent history of GDM.Retrospective analysis of the medical records of women with a recent history of GDM diagnosed in a universal two-step screening strategy with the 2013 WHO criteria. All women with a history of GDM are advised to undergo a 75g oral glucose tolerance test (OGTT around 12 weeks postpartum. Indices of insulin sensitivity (the Matsuda index and the reciprocal of the homeostasis model assessment of insulin resistance, 1/HOMA-IR and an index of beta-cell function, the Insulin Secretion-Sensitivity Index-2 (ISSI-2 were calculated based on the OGTT postpartum. Multivariable logistic regression was used to adjust for confounders such as age, BMI, ethnicity and breastfeeding.Of the 191 women with GDM, 29.3% (56 did not attend the scheduled postpartum OGTT. These women had a higher BMI (28.6 ±6.8 vs. 26.2 ± 5.6, p = 0.015, were more often from an ethnic minority (EM background (41.1% vs. 25.2%, p = 0.029 and smoked more often during pregnancy (14.3% vs. 2.2%, p = 0.001 than women who attended the OGTT postpartum. Of all women (135 who received an OGTT postpartum, 42.2% (57 had prediabetes (11.9% impaired fasting glucose, 24.4% impaired glucose tolerance and 5.9% both impaired fasting and impaired glucose tolerance and 1.5% (2 had overt diabetes. Compared to women with a normal OGTT postpartum, women with glucose intolerance were older (32.5±4.3 vs. 30.8±4.8 years, p = 0.049, were more often obese (34.5% vs. 17.3%, p = 0.023, were more often from an EM background (33.9% vs. 18.4%, p = 0.040, less often breastfed (69.5% vs. 84.2%, p = 0.041 and had more often an abnormal fasting glycaemia

  5. Resolution of glucose intolerance in long-term high-fat, high-sucrose-fed mice.

    Science.gov (United States)

    Kowalski, Greg M; Kraakman, Michael J; Mason, Shaun A; Murphy, Andrew J; Bruce, Clinton R

    2017-06-01

    The high-fat, high-sucrose diet (HFSD)-fed C57Bl/6 mouse is a widely used model of prediabetes. However, studies typically implement a relatively short dietary intervention lasting between 4 and 16 weeks; as a result, little is known about how a long-term HFSD influences the metabolic profile of these mice. Therefore, the aim of this investigation was to examine the effects of consuming a HFSD for 42 weeks on the development of hyperinsulinaemia and glucose intolerance in male C57Bl/6 mice. Two cohorts of HFSD mice were studied at independent institutes and they underwent an oral glucose tolerance test (OGTT) with measures of plasma insulin and free fatty acids (FFA). Age-matched chow-fed control mice were also studied. The HFSD-fed mice were hyperinsulinaemic and grossly obese, being over 25 g heavier than chow-fed mice, which was due to a marked expansion of subcutaneous adipose tissue. This was associated with a 3-fold increase in liver lipid content. Glucose tolerance, however, was either the same or better than control mice due to the preservation of glucose disposal as revealed by a dynamic stable isotope-labelled OGTT. In addition, plasma FFAs were suppressed to lower levels in HFSD mice during the OGTT. In conclusion, we have made the paradoxical observation that long-term HFSD feeding results in the resolution of glucose intolerance in the C57Bl/6 mouse. Mechanistically, we propose that the gross expansion of subcutaneous adipose tissue increases the glucose disposal capacity of the HFSD-fed mouse, which overcomes the prevailing insulin resistance to improve glucose tolerance. © 2017 Society for Endocrinology.

  6. Glucose intolerance in early postpartum in women with gestational diabetes: Who is at increased risk?

    Science.gov (United States)

    Leuridan, Liesbeth; Wens, Johan; Devlieger, Roland; Verhaeghe, Johan; Mathieu, Chantal; Benhalima, Katrien

    2015-08-01

    Women with a history of gestational diabetes (GDM) have an increased risk for developing type 2 diabetes in the years after the index pregnancy. Some women with GDM already develop glucose intolerance in early postpartum. The best screening strategy for glucose intolerance in early postpartum among women with a history of GDM is still debated. We review the most important risk factors of women with GDM to develop glucose intolerance within one year postpartum. We also discuss the current recommendations for screening in early postpartum and the many challenges to organize postpartum follow up in primary care. Copyright © 2015 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  7. Arsenate-induced maternal glucose intolerance and neural tube defects in a mouse model

    International Nuclear Information System (INIS)

    Hill, Denise S.; Wlodarczyk, Bogdan J.; Mitchell, Laura E.; Finnell, Richard H.

    2009-01-01

    Background: Epidemiological studies have linked environmental arsenic (As) exposure to increased type 2 diabetes risk. Periconceptional hyperglycemia is a significant risk factor for neural tube defects (NTDs), the second most common structural birth defect. A suspected teratogen, arsenic (As) induces NTDs in laboratory animals. Objectives: We investigated whether maternal glucose homeostasis disruption was responsible for arsenate-induced NTDs in a well-established dosing regimen used in studies of arsenic's teratogenicity in early neurodevelopment. Methods: We evaluated maternal intraperitoneal (IP) exposure to As 9.6 mg/kg (as sodium arsenate) in LM/Bc/Fnn mice for teratogenicity and disruption of maternal plasma glucose and insulin levels. Selected compounds (insulin pellet, sodium selenate (SS), N-acetyl cysteine (NAC), L-methionine (L-Met), N-tert-Butyl-α-phenylnitrone (PBN)) were investigated for their potential to mitigate arsenate's effects. Results: Arsenate caused significant glucose elevation during an IP glucose tolerance test (IPGTT). Insulin levels were not different between arsenate and control dams before (arsenate, 0.55 ng/dl; control, 0.48 ng/dl) or after glucose challenge (arsenate, 1.09 ng/dl; control, 0.81 ng/dl). HOMA-IR index was higher for arsenate (3.9) vs control (2.5) dams (p = 0.0260). Arsenate caused NTDs (100%, p < 0.0001). Insulin pellet and NAC were the most successful rescue agents, reducing NTD rates to 45% and 35%. Conclusions: IPGTT, insulin assay, and HOMA-IR results suggest a modest failure of glucose stimulated insulin secretion and insulin resistance characteristic of glucose intolerance. Insulin's success in preventing arsenate-induced NTDs provides evidence that these arsenate-induced NTDs are secondary to elevated maternal glucose. The NAC rescue, which did not restore maternal glucose or insulin levels, suggests oxidative disruption plays a role.

  8. Glucose tolerance in Papua New Guinea: ethnic differences, association with environmental and behavioural factors and the possible emergence of glucose intolerance in a highland community.

    Science.gov (United States)

    King, H; Finch, C; Collins, A; Koki, G; King, L F; Heywood, P; Zimmet, P

    1989-08-21

    That Melanesians of non-Austronesian genetic ancestry may be relatively resistant to glucose intolerance was supported by the results of a study of two semitraditional non-Austronesian villages in the Papua New Guinean highlands in 1983, in which an absence of diabetes and a high degree of glucose tolerance and insulin sensitivity were observed. The second of this series of surveys was conducted in 1985 in three non-traditional communities: a periurban, non-Austronesian village in the highlands, and rural and periurban Austronesian villages in coastal locations. Although an absence of diabetes was demonstrated once again in the highlanders, these periurban subjects showed an unexpectedly high insulin response which may be a precursor of glucose intolerance. The notion that highland communities that are living in non-traditional circumstances in Papua New Guinea presently are in "metabolic transition" towards diabetes and other non-communicable diseases, if correct, is of importance to the public health of the nation. In the periurban, coastal-dwelling Austronesians, diabetes with severe hyperglycaemia was demonstrated, and there was some evidence of a secular trend towards increasing glucose intolerance. The two-hour plasma glucose concentrations were shown to be associated with obesity, modernity and Seventh-Day Adventist religious persuasion. However, important and unexplained differences in glucose tolerance remained between rural and periurban coastal dwellers after taking these factors into account.

  9. Association between whole blood mercury and glucose intolerance among adult Inuit in Greenland

    DEFF Research Database (Denmark)

    Jeppesen, Charlotte; Valera, Beatriz; Nielsen, Nina O

    2015-01-01

    OBJECTIVES: The Arctic diet is partly constituted by traditional food characterized by top predator animals such as whales, walrus, and seals with high mercury content. Mercury exposure has been associated with glucose intolerance in Western populations. We studied the association between whole...... blood mercury and glucose intolerance in a highly exposed non-Western population METHODS: Cross-sectional study of 2640 Inuit (18+ years) with information on ancestry, smoking, waist circumference, total energy intake, and physical activity. Mercury, fasting- and 2-h plasma glucose, insulin, and c...

  10. The effect of altered gut flora on glucose intolerance in C57BL/6NTac mice

    DEFF Research Database (Denmark)

    Rune, Ida; Hansen, Axel Jacob Kornerup; Ellekilde, Merete

    Background Recent studies have shown that long term broad spectrum antibiotic treatment improves glucose tolerance in mice. We hypothesize that it is primarily the early life altering of the gut microbiota, which will have an impact on glucose intolerance. Study setup 40 C57BL/6NTac mice were...

  11. Factors predicting early postpartum glucose intolerance in Japanese women with gestational diabetes mellitus: decision-curve analysis.

    Science.gov (United States)

    Kondo, M; Nagao, Y; Mahbub, M H; Tanabe, Tsuyoshi; Tanizawa, Y

    2018-04-29

    To identify factors predicting early postpartum glucose intolerance in Japanese women with gestational diabetes mellitus, using decision-curve analysis. A retrospective cohort study was performed. The participants were 123 Japanese women with gestational diabetes who underwent 75-g oral glucose tolerance tests at 8-12 weeks after delivery. They were divided into a glucose intolerance and a normal glucose tolerance group based on postpartum oral glucose tolerance test results. Analysis of the pregnancy oral glucose tolerance test results showed predictive factors for postpartum glucose intolerance. We also evaluated the clinical usefulness of the prediction model based on decision-curve analysis. Of 123 women, 78 (63.4%) had normoglycaemia and 45 (36.6%) had glucose intolerance. Multivariable logistic regression analysis showed insulinogenic index/fasting immunoreactive insulin and summation of glucose levels, assessed during pregnancy oral glucose tolerance tests (total glucose), to be independent risk factors for postpartum glucose intolerance. Evaluating the regression models, the best discrimination (area under the curve 0.725) was obtained using the basic model (i.e. age, family history of diabetes, BMI ≥25 kg/m 2 and use of insulin during pregnancy) plus insulinogenic index/fasting immunoreactive insulin intolerance. Insulinogenic index/fasting immunoreactive insulin calculated using oral glucose tolerance test results during pregnancy is potentially useful for predicting early postpartum glucose intolerance in Japanese women with gestational diabetes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  12. Intestinal Ralstonia pickettii augments glucose intolerance in obesity.

    Directory of Open Access Journals (Sweden)

    Shanthadevi D Udayappan

    Full Text Available An altered intestinal microbiota composition has been implicated in the pathogenesis of metabolic disease including obesity and type 2 diabetes mellitus (T2DM. Low grade inflammation, potentially initiated by the intestinal microbiota, has been suggested to be a driving force in the development of insulin resistance in obesity. Here, we report that bacterial DNA is present in mesenteric adipose tissue of obese but otherwise healthy human subjects. Pyrosequencing of bacterial 16S rRNA genes revealed that DNA from the Gram-negative species Ralstonia was most prevalent. Interestingly, fecal abundance of Ralstonia pickettii was increased in obese subjects with pre-diabetes and T2DM. To assess if R. pickettii was causally involved in development of obesity and T2DM, we performed a proof-of-concept study in diet-induced obese (DIO mice. Compared to vehicle-treated control mice, R. pickettii-treated DIO mice had reduced glucose tolerance. In addition, circulating levels of endotoxin were increased in R. pickettii-treated mice. In conclusion, this study suggests that intestinal Ralstonia is increased in obese human subjects with T2DM and reciprocally worsens glucose tolerance in DIO mice.

  13. Long-term ketogenic diet causes glucose intolerance and reduced β- and α-cell mass but no weight loss in mice

    NARCIS (Netherlands)

    Ellenbroek, Johanne H; van Dijck, Laura; Töns, Hendrica A; Rabelink, Ton J; Carlotti, Françoise; Ballieux, Bart E P B; de Koning, Eelco J P

    2014-01-01

    High-fat, low-carbohydrate ketogenic diets (KD) are used for weight loss and for treatment of refractory epilepsy. Recently, short-time studies in rodents have shown that, besides their beneficial effect on body weight, KD lead to glucose intolerance and insulin resistance. However, the long-term

  14. Prevalence of glucose intolerance and associated risk factors in rural and urban populations of different ethnic groups in Kenya

    DEFF Research Database (Denmark)

    Christensen, D.; Friis, H.; Mwaniki, D.

    2009-01-01

    Objective: To assess the prevalence of glucose intolerance in rural and urban Kenyan populations and in different ethnic groups. Further, to identify associations between lifestyle risk factors and glucose intolerance. Research design and methods: A cross-sectional study included an opportunity...... intolerance among the rural ethnic groups. High BMI, WC, AFA, abdominal visceral and subcutaneous fat thickness, low fitness and physical activity, frequent alcohol consumption, and urban residence were associated with glucose intolerance. Conclusions: The prevalence of diabetes and IGT among different Kenyan...

  15. Impact of glucose intolerance on coronary calcified lesions evaluated using multislice computed tomography

    International Nuclear Information System (INIS)

    Nomura, Kyoko; Ohwaki, Kazuhiro; Yano, Eiji; Yamanouchi, Toshikazu; Kim, Gwang U.

    2007-01-01

    Metabolic syndrome has the unique concept that the common occurrence of individual disease components increases the risk of coronary artery disease (CAD). However, some studies suggest that the burden of different CAD risk factors is not equal, and focusing on the whole set of risk factors might neglect the impact of individual factors that could be useful targets for prophylactic therapies. The purpose of this study was to investigate the effect of glucose intolerance on CAD using multislice computed tomography (MSCT). Ninety-eight consecutive patients with at least one traditional CAD risk factor who visited a municipal hospital were enrolled in this study. The risk factors were impaired glucose tolerance (fasting glucose≥110 mg/dl or patients with diabetes), low high-density lipoprotein cholesterol (HDL-C, 25 kg/m 2 for men and >23 kg/m 2 for women). CAD was determined by the presence of either stenoses, non-calcified plaques or calcified lesions. The following risk factors were significantly related in univariate logistic models: glucose intolerance and coronary calcified lesions (p=0.001), and hypertriglycemia and non-calcified plaque lesions (p=0.048). Multivariate models showed that glucose intolerance was significantly associated with calcified lesions, even after adjustment for gender, age, low HDL-C, hypertriglycemia, hypertension, and obesity (p=0.018). Our results suggest that glucose intolerance might be closely related to the presence of coronary calcified lesions among traditional CAD risk factors. (author)

  16. Delayed ß-cell response and glucose intolerance in young women with Turner syndrome

    DEFF Research Database (Denmark)

    Hjerrild, Britta Eilersen; Holst, Jens Juul; Juhl, Claus

    2011-01-01

    similar. In addition we found low IGF-I, higher levels of cortisol and norepinephrine and an increased waist-hip ratio in TS. CONCLUSIONS: Young normal weight TS women show significant glucose intolerance in spite of normal insulin secretion during hyperglycaemic clamping and normal insulin sensitivity...

  17. The prevalence of glucose inTolerance among anTenaTal clienTs ...

    African Journals Online (AJOL)

    2011-09-09

    Sep 9, 2011 ... Exclusion criteria: Clients who had pre-gestational diabetes mellitus, those already diagnosed with glucose intolerance in the current pregnancy or in previous pregnancy, clients who did not consent and clients on medications for chronic treatment. Sampling frame: This consisted of antenatal mothers.

  18. A cross-sectional study of the association between persistent organic pollutants and glucose intolerance among Greenland Inuit

    DEFF Research Database (Denmark)

    Jørgensen, Marit Eika; Borch-Johnsen, K; Bjerregaard, P

    2008-01-01

    prevalence over the last 30 years. Thus the aim was to study the association between POPs and glucose intolerance and markers of insulin resistance and insulin secretion using a population-based design. METHODS: From 1999 to 2002 the Greenland population study was carried out among adult Inuit living...... in Greenland. The examination included a 75 g OGTT, anthropometric measurements, a structured interview, and blood tests. Plasma glucose and serum insulin were analysed, and three defined subclasses of POPs were analysed in a subgroup. Associations were adjusted for age, sex, waist circumference, Inuit...... heritage, cigarette smoking, alcohol consumption and educational level. RESULTS: Data on POPs were available on 692 individuals, 305 men (mean age 50 years) and 387 women (mean age 49 years). The prevalence of diabetes was 10.3%, and 10.5% had impaired glucose tolerance. The concentrations of several POPs...

  19. Ursolic acid increases skeletal muscle and brown fat and decreases diet-induced obesity, glucose intolerance and fatty liver disease.

    Directory of Open Access Journals (Sweden)

    Steven D Kunkel

    Full Text Available Skeletal muscle Akt activity stimulates muscle growth and imparts resistance to obesity, glucose intolerance and fatty liver disease. We recently found that ursolic acid increases skeletal muscle Akt activity and stimulates muscle growth in non-obese mice. Here, we tested the hypothesis that ursolic acid might increase skeletal muscle Akt activity in a mouse model of diet-induced obesity. We studied mice that consumed a high fat diet lacking or containing ursolic acid. In skeletal muscle, ursolic acid increased Akt activity, as well as downstream mRNAs that promote glucose utilization (hexokinase-II, blood vessel recruitment (Vegfa and autocrine/paracrine IGF-I signaling (Igf1. As a result, ursolic acid increased skeletal muscle mass, fast and slow muscle fiber size, grip strength and exercise capacity. Interestingly, ursolic acid also increased brown fat, a tissue that shares developmental origins with skeletal muscle. Consistent with increased skeletal muscle and brown fat, ursolic acid increased energy expenditure, leading to reduced obesity, improved glucose tolerance and decreased hepatic steatosis. These data support a model in which ursolic acid reduces obesity, glucose intolerance and fatty liver disease by increasing skeletal muscle and brown fat, and suggest ursolic acid as a potential therapeutic approach for obesity and obesity-related illness.

  20. Insulin signal transduction in skeletal muscle from glucose-intolerant relatives of type 2 diabetic patients [corrected

    DEFF Research Database (Denmark)

    Storgaard, H; Song, X M; Jensen, C B

    2001-01-01

    To determine whether defects in the insulin signal transduction cascade are present in skeletal muscle from prediabetic individuals, we excised biopsies from eight glucose-intolerant male first-degree relatives of patients with type 2 diabetes (IGT relatives) and nine matched control subjects...... phosphorylation in control subjects and IGT relatives, with a tendency for reduced phosphorylation in IGT relatives (P = 0.12). In conclusion, aberrant phosphorylation/activity of IRS-1, PI 3-kinase, and Akt is observed in skeletal muscle from relatives of patients with type 2 diabetes with IGT. However...... resistance in skeletal muscle from relatives of patients with type 2 diabetes....

  1. Muscle histidine-containing dipeptides are elevated by glucose intolerance in both rodents and men.

    Directory of Open Access Journals (Sweden)

    Sanne Stegen

    Full Text Available Muscle carnosine and its methylated form anserine are histidine-containing dipeptides. Both dipeptides have the ability to quench reactive carbonyl species and previous studies have shown that endogenous tissue levels are decreased in chronic diseases, such as diabetes.Rodent study: Skeletal muscles of rats and mice were collected from 4 different diet-intervention studies, aiming to induce various degrees of glucose intolerance: 45% high-fat feeding (male rats, 60% high-fat feeding (male rats, cafeteria feeding (male rats, 70% high-fat feeding (female mice. Body weight, glucose-tolerance and muscle histidine-containing dipeptides were assessed. Human study: Muscle biopsies were taken from m. vastus lateralis in 35 males (9 lean, 8 obese, 9 prediabetic and 9 newly diagnosed type 2 diabetic patients and muscle carnosine and gene expression of muscle fiber type markers were measured.Diet interventions in rodents (cafeteria and 70% high-fat feeding induced increases in body weight, glucose intolerance and levels of histidine-containing dipeptides in muscle. In humans, obese, prediabetic and diabetic men had increased muscle carnosine content compared to the lean (+21% (p>0.1, +30% (p<0.05 and +39% (p<0.05, respectively. The gene expression of fast-oxidative type 2A myosin heavy chain was increased in the prediabetic (1.8-fold, p<0.05 and tended to increase in the diabetic men (1.6-fold, p = 0.07, compared to healthy lean subjects.Muscle histidine-containing dipeptides increases with progressive glucose intolerance, in male individuals (cross-sectional. In addition, high-fat diet-induced glucose intolerance was associated with increased muscle histidine-containing dipeptides in female mice (interventional. Increased muscle carnosine content might reflect fiber type composition and/or act as a compensatory mechanism aimed at preventing cell damage in states of impaired glucose tolerance.

  2. The effect of altered gut flora on glucose intolerance in C57BL/6NTac mice

    DEFF Research Database (Denmark)

    Rune, Ida; Nielsen, Dennis Sandris; Hansen, Axel Jacob Kornerup

    Background Recent studies have shown that long term broad spectrum antibiotic treatment improves glucose tolerance in mice. We hypothesize that it is primarily the early life altering of the gut microbiota, which will have an impact on glucose intolerance. Study setup 40 C57BL/6NTac mice were...... no clustering was evident. Discussion Our results substantiate the theory implying an effect of gut microbiota on glucose tolerance. Furthermore, it seems evident that a window of opportunity for altering the host-microbial interaction response exists only in early life when host immunity is still developing...

  3. Dietary patterns in Greenland and their relationship with type 2 diabetes mellitus and glucose intolerance

    DEFF Research Database (Denmark)

    Jeppesen, Charlotte; Bjerregaard, Peter; Jørgensen, Marit Eika

    2013-01-01

    glucose (IFG). DESIGN: Cross-sectional design with a priori derived dietary patterns from an FFQ resulted in five patterns: imported meat (n 196), traditional food (n 601), balanced diet (n 126), unhealthy diet (n 652) and standard diet (n 799). SETTING: Associations between dietary patterns and glucose...... fasting plasma glucose (mean 5·73 (95 % CI 5·68, 5·78) mmol/l, P diet gave significantly higher odds for IFG and T2DM than the balanced diet, imported meat diet, standard diet and unhealthy diet. CONCLUSIONS: Traditional...... food was positively associated with T2DM, IFG and fasting plasma glucose, and negatively associated with β-cell function, compared with a standard diet. The imported meat diet seemed the best in relation to glucose intolerance, with lowest fasting plasma glucose and lowest odds for IFG and T2DM....

  4. Glucose intolerance associated with hypoxia in people living at high altitudes in the Tibetan highland.

    Science.gov (United States)

    Okumiya, Kiyohito; Sakamoto, Ryota; Ishimoto, Yasuko; Kimura, Yumi; Fukutomi, Eriko; Ishikawa, Motonao; Suwa, Kuniaki; Imai, Hissei; Chen, Wenling; Kato, Emiko; Nakatsuka, Masahiro; Kasahara, Yoriko; Fujisawa, Michiko; Wada, Taizo; Wang, Hongxin; Dai, Qingxiang; Xu, Huining; Qiao, Haisheng; Ge, Ri-Li; Norboo, Tsering; Tsering, Norboo; Kosaka, Yasuyuki; Nose, Mitsuhiro; Yamaguchi, Takayoshi; Tsukihara, Toshihiro; Ando, Kazuo; Inamura, Tetsuya; Takeda, Shinya; Ishine, Masayuki; Otsuka, Kuniaki; Matsubayashi, Kozo

    2016-02-23

    To clarify the association between glucose intolerance and high altitudes (2900-4800 m) in a hypoxic environment in Tibetan highlanders and to verify the hypothesis that high altitude dwelling increases vulnerability to diabetes mellitus (DM) accelerated by lifestyle change or ageing. Cross-sectional epidemiological study on Tibetan highlanders. We enrolled 1258 participants aged 40-87 years. The rural population comprised farmers in Domkhar (altitude 2900-3800 m) and nomads in Haiyan (3000-3100 m), Ryuho (4400 m) and Changthang (4300-4800 m). Urban area participants were from Leh (3300 m) and Jiegu (3700 m). Participants were classified into six glucose tolerance-based groups: DM, intermediate hyperglycaemia (IHG), normoglycaemia (NG), fasting DM, fasting IHG and fasting NG. Prevalence of glucose intolerance was compared in farmers, nomads and urban dwellers. Effects of dwelling at high altitude or hypoxia on glucose intolerance were analysed with the confounding factors of age, sex, obesity, lipids, haemoglobin, hypertension and lifestyle, using multiple logistic regression. The prevalence of DM (fasting DM)/IHG (fasting IHG) was 8.9% (6.5%)/25.1% (12.7%), respectively, in all participants. This prevalence was higher in urban dwellers (9.5% (7.1%)/28.5% (11.7%)) and in farmers (8.5% (6.1%)/28.5% (18.3%)) compared with nomads (8.2% (5.7%)/15.7% (9.7%)) (p=0.0140/0.0001). Dwelling at high altitude was significantly associated with fasting IHG+fasting DM/fasting DM (ORs for >4500 and 3500-4499 m were 3.59/4.36 and 2.07/1.76 vs intolerance. Socioeconomic factors, hypoxaemia and the effects of altitudes >3500 m play a major role in the high prevalence of glucose intolerance in highlanders. Tibetan highlanders may be vulnerable to glucose intolerance, with polycythaemia as a sign of poor hypoxic adaptation, accelerated by lifestyle change and ageing. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please

  5. Exposure to the common food additive carrageenan leads to glucose intolerance, insulin resistance and inhibition of insulin signalling in HepG2 cells and C57BL/6J mice.

    Science.gov (United States)

    Bhattacharyya, S; O-Sullivan, I; Katyal, S; Unterman, T; Tobacman, J K

    2012-01-01

    The aim of this study was to determine the impact of the common food additive carrageenan (E407) on glucose tolerance, insulin sensitivity and insulin signalling in a mouse model and human hepatic cells, since carrageenan is known to cause inflammation through interaction with toll-like receptor (TLR)4, which is associated with inflammation in diabetes. Male C57BL/6J mice were given carrageenan (10 mg/l) in their drinking water, and underwent a glucose tolerance test (GTT), an insulin tolerance test (ITT) and an ante-mortem intraperitoneal insulin injection. HepG2 cells were exposed to carrageenan (1 mg/l × 24 h) and insulin. Levels of phospho(Ser473)-protein kinase B (Akt), phospho(Ser307)-IRS1, phosphoinositide 3-kinase (PI3K) activity and phospho(Ser32)-inhibitor of κB (IκBα) were determined by western blotting and ELISA. Glucose tolerance was significantly impaired in carrageenan-treated 12-week-old mice compared with untreated controls at all time points (n = 12; p < 0.0001). Baseline insulin and insulin levels at 30 min after taking glucose during the GTT were significantly higher following carrageenan treatment. During the ITT, glucose levels declined by more than 80% in controls, but not in carrageenan-treated mice. Carrageenan exposure completely inhibited insulin-induced increases in phospho-(Ser473)-Akt and PI3K activity in vivo in mouse liver and in human HepG2 cells. Carrageenan increased phospho(Ser307)-IRS1 levels, and this was blocked when carrageenan-induced inflammation was inhibited. This is the first report of the impact of carrageenan on glucose tolerance and indicates that carrageenan impairs glucose tolerance, increases insulin resistance and inhibits insulin signalling in vivo in mouse liver and human HepG2 cells. These effects may result from carrageenan-induced inflammation. The results demonstrate extra-colonic manifestations of ingested carrageenan and suggest that carrageenan in the human diet may contribute to the

  6. Gut microbial degradation of organophosphate insecticides-induces glucose intolerance via gluconeogenesis.

    Science.gov (United States)

    Velmurugan, Ganesan; Ramprasath, Tharmarajan; Swaminathan, Krishnan; Mithieux, Gilles; Rajendhran, Jeyaprakash; Dhivakar, Mani; Parthasarathy, Ayothi; Babu, D D Venkatesh; Thumburaj, Leishman John; Freddy, Allen J; Dinakaran, Vasudevan; Puhari, Shanavas Syed Mohamed; Rekha, Balakrishnan; Christy, Yacob Jenifer; Anusha, Sivakumar; Divya, Ganesan; Suganya, Kannan; Meganathan, Boominathan; Kalyanaraman, Narayanan; Vasudevan, Varadaraj; Kamaraj, Raju; Karthik, Maruthan; Jeyakumar, Balakrishnan; Abhishek, Albert; Paul, Eldho; Pushpanathan, Muthuirulan; Rajmohan, Rajamani Koushick; Velayutham, Kumaravel; Lyon, Alexander R; Ramasamy, Subbiah

    2017-01-24

    Organophosphates are the most frequently and largely applied insecticide in the world due to their biodegradable nature. Gut microbes were shown to degrade organophosphates and cause intestinal dysfunction. The diabetogenic nature of organophosphates was recently reported but the underlying molecular mechanism is unclear. We aimed to understand the role of gut microbiota in organophosphate-induced hyperglycemia and to unravel the molecular mechanism behind this process. Here we demonstrate a high prevalence of diabetes among people directly exposed to organophosphates in rural India (n = 3080). Correlation and linear regression analysis reveal a strong association between plasma organophosphate residues and HbA1c but no association with acetylcholine esterase was noticed. Chronic treatment of mice with organophosphate for 180 days confirms the induction of glucose intolerance with no significant change in acetylcholine esterase. Further fecal transplantation and culture transplantation experiments confirm the involvement of gut microbiota in organophosphate-induced glucose intolerance. Intestinal metatranscriptomic and host metabolomic analyses reveal that gut microbial organophosphate degradation produces short chain fatty acids like acetic acid, which induces gluconeogenesis and thereby accounts for glucose intolerance. Plasma organophosphate residues are positively correlated with fecal esterase activity and acetate level of human diabetes. Collectively, our results implicate gluconeogenesis as the key mechanism behind organophosphate-induced hyperglycemia, mediated by the organophosphate-degrading potential of gut microbiota. This study reveals the gut microbiome-mediated diabetogenic nature of organophosphates and hence that the usage of these insecticides should be reconsidered.

  7. Plasma kinetics of an LDL-like nanoemulsion and lipid transfer to HDL in subjects with glucose intolerance

    Directory of Open Access Journals (Sweden)

    Marina P Bertato

    2012-01-01

    Full Text Available OBJECTIVE: Glucose intolerance is frequently associated with an altered plasma lipid profile and increased cardiovascular disease risk. Nonetheless, lipid metabolism is scarcely studied in normolipidemic glucose-intolerant patients. The aim of this study was to investigate whether important lipid metabolic parameters, such as the kinetics of LDL free and esterified cholesterol and the transfer of lipids to HDL, are altered in glucose-intolerant patients with normal plasma lipids. METHODS: Fourteen glucose-intolerant patients and 15 control patients were studied; none of the patients had cardiovascular disease manifestations, and they were paired for age, sex, race and co-morbidities. A nanoemulsion resembling a LDL lipid composition (LDE labeled with 14C-cholesteryl ester and ³H-free cholesterol was intravenously injected, and blood samples were collected over a 24-h period to determine the fractional clearance rate of the labels by compartmental analysis. The transfer of free and esterified cholesterol, triglycerides and phospholipids from the LDE to HDL was measured by the incubation of the LDE with plasma and radioactivity counting of the supernatant after chemical precipitation of non-HDL fractions. RESULTS: The levels of LDL, non-HDL and HDL cholesterol, triglycerides, apo A1 and apo B were equal in both groups. The 14C-esterified cholesterol fractional clearance rate was not different between glucose-intolerant and control patients, but the ³H-free-cholesterol fractional clearance rate was greater in glucose-intolerant patients than in control patients. The lipid transfer to HDL was equal in both groups. CONCLUSION: In these glucose-intolerant patients with normal plasma lipids, a faster removal of LDE free cholesterol was the only lipid metabolic alteration detected in our study. This finding suggests that the dissociation of free cholesterol from lipoprotein particles occurs in normolipidemic glucose intolerance and may participate in

  8. CORRELATION BETWEEN GUT MICROBIOTA AND DEVELOPMENT OF GLUCOSE INTOLERANCE IN B6.V-Lepob/J LEPTIN DEFICIENT MICE

    DEFF Research Database (Denmark)

    Ellekilde, Merete; Hansen, Camilla Hartmann Friis; Nielsen, Dennis Sandris

    -Lepob/J leptin deficient mouse, a model of severe obesity and type 2 diabetes, was correlated with development of glucose intolerance. GM composition was analyzed by means of denaturing gradient gel electrophoresis (DGGE), a culture independent approach, separating PCR-derived DNA amplicons of bacterial 16S r......RNA. Disease development was monitored by weekly weight and blood glucose measurements supplemented with measurements of oral glucose tolerance, HbA1c%, plasma insulin and plasma cytokines. A significant correlation was demonstrated between GM composition and glucose intolerance. Also, a significant...... correlation was found between blood glucose, HbA1c% and glucose intolerance and the pro-inflammatory cytokine IL-12, supporting the correlation found between gut and disease, as IL-12 is secreted after microbial stimulation of immunological cells – e.g. In the gut. Further investigations concerning...

  9. Continuous Blood Glucose Monitoring May Detect Carotid Occlusion Intolerance during Carotid Artery Stenting.

    Science.gov (United States)

    Hiramatsu, Ryo; Furuse, Motomasa; Yagi, Ryokichi; Ohmura, Tomohisa; Ohnishi, Hiroyuki; Ikeda, Naokado; Nonoguchi, Naosuke; Kawabata, Shinji; Miyachi, Shigeru; Kuroiwa, Toshihiko

    2018-02-05

    The frequency of the occurrence of adverse events associated with carotid artery stenting (CAS) is usually low, but serious adverse events such as cerebral hyperperfusion syndrome (CHS) may occur. Real-time monitoring is ideal for the early detection of adverse events during the surgical procedure. This study aimed to evaluate continuous blood glucose (BG) monitoring for the detection of adverse events during CAS. Forty patients undergoing scheduled CAS were prospectively enrolled. An artificial pancreas was used for continuous BG monitoring (once per minute), using venous blood extracted at a rate of 2 mL/hr during CAS. The primary endpoint was a correlation between BG change and adverse events. CAS was discontinued in 1 patient, and BG was not measured in 5 patients (12.5%) because of the inability to extract blood. Among 34 evaluable patients, no patient developed CHS, but 3 patients (9%) experienced carotid occlusion intolerance. During CAS, BG was significantly higher in patients with carotid occlusion intolerance (median: 5 mg/dL) than in patients without carotid occlusion intolerance (median: 0 mg/dL) (P = 0.0221). A cutoff BG value ≥4 mg/dL during CAS showed 50% sensitivity and 100% specificity for the detection of carotid occlusion intolerance. There was no significant correlation between BG change and other adverse events. BG elevation may help detect carotid occlusion intolerance although it is still unknown whether BG monitoring can detect CHS. Further studies should validate that a cutoff BG elevation value of ≥4 mg/dL during CAS indicates carotid occlusion intolerance. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Cytosolic Pellino-1-Mediated K63-Linked Ubiquitination of IRF5 in M1 Macrophages Regulates Glucose Intolerance in Obesity

    Directory of Open Access Journals (Sweden)

    Donghyun Kim

    2017-07-01

    Full Text Available IRF5 is a signature transcription factor that induces M1 macrophage polarization. However, little is known regarding cytosolic proteins that induce IRF5 activation for M1 polarization. Here, we report the interaction between ubiquitin E3 ligase Pellino-1 and IRF5 in the cytoplasm, which increased nuclear translocation of IRF5 by K63-linked ubiquitination in human and mouse M1 macrophages. LPS and/or IFN-γ increased Pellino-1 expression, and M1 polarization was attenuated in Pellino-1-deficient macrophages in vitro and in vivo. Defective M1 polarization in Pellino-1-deficient macrophages improved glucose intolerance in mice fed a high-fat diet. Furthermore, macrophages in adipose tissues from obese humans exhibited increased Pellino-1 expression and IRF5 nuclear translocation compared with nonobese subjects, and these changes are associated with insulin resistance index. This study demonstrates that cytosolic Pellino-1-mediated K63-linked ubiquitination of IRF5 in M1 macrophages regulates glucose intolerance in obesity, suggesting a cytosolic mediator function of Pellino-1 in TLR4/IFN-γ receptor-IRF5 axis during M1 polarization.

  11. A model of type 2 diabetes in the guinea pig using sequential diet-induced glucose intolerance and streptozotocin treatment

    Directory of Open Access Journals (Sweden)

    Brendan K. Podell

    2017-02-01

    Full Text Available Type 2 diabetes is a leading cause of morbidity and mortality among noncommunicable diseases, and additional animal models that more closely replicate the pathogenesis of human type 2 diabetes are needed. The goal of this study was to develop a model of type 2 diabetes in guinea pigs, in which diet-induced glucose intolerance precedes β-cell cytotoxicity, two processes that are crucial to the development of human type 2 diabetes. Guinea pigs developed impaired glucose tolerance after 8 weeks of feeding on a high-fat, high-carbohydrate diet, as determined by oral glucose challenge. Diet-induced glucose intolerance was accompanied by β-cell hyperplasia, compensatory hyperinsulinemia, and dyslipidemia with hepatocellular steatosis. Streptozotocin (STZ treatment alone was ineffective at inducing diabetic hyperglycemia in guinea pigs, which failed to develop sustained glucose intolerance or fasting hyperglycemia and returned to euglycemia within 21 days after treatment. However, when high-fat, high-carbohydrate diet-fed guinea pigs were treated with STZ, glucose intolerance and fasting hyperglycemia persisted beyond 21 days post-STZ treatment. Guinea pigs with diet-induced glucose intolerance subsequently treated with STZ demonstrated an insulin-secretory capacity consistent with insulin-independent diabetes. This insulin-independent state was confirmed by response to oral antihyperglycemic drugs, metformin and glipizide, which resolved glucose intolerance and extended survival compared with guinea pigs with uncontrolled diabetes. In this study, we have developed a model of sequential glucose intolerance and β-cell loss, through high-fat, high-carbohydrate diet and extensive optimization of STZ treatment in the guinea pig, which closely resembles human type 2 diabetes. This model will prove useful in the study of insulin-independent diabetes pathogenesis with or without comorbidities, where the guinea pig serves as a relevant model species.

  12. Dysregulation of the Glutamine Transporter Slc38a3 (SNAT3 and Ammoniagenic Enzymes in Obese, Glucose-Intolerant Mice

    Directory of Open Access Journals (Sweden)

    Stephanie M. Busque

    2014-08-01

    Full Text Available Background/Aims: Uric acid nephrolithiasis is prevalent among patients with type 2 diabetes and metabolic syndrome; it is correlated with an acidic urine and lower urinary ammonium excretion and is likely associated with insulin resistance. Insulin stimulates ammoniagenesis in renal cell lines via increased phosphate-dependent glutaminase (PDG activity and glutamine metabolism. Ammonium excretion into the proximal tubule is mediated at least in part by the Na+/H+-exchanger NHE3 and in the collecting duct involving the Rhesus protein RhCG. Here we tested, whether obesity and insulin resistance in a diet-induced mouse model could contribute to deranged ammonium excretion. Methods: Obesity was induced by diet in mice and the impact on key molecules of proximal tubular ammoniagenesis and urinary acid excretion tested. Results: Diet-induced obesity was confirmed by pathological intraperitoneal glucose tolerance tests (IPGTT. Three groups of mice were compared: control mice; obese, glucose-intolerant with abnormal IPGTT (O-GI; or moderate weight with normal IPGTT (Non-Responders, NR. Basal urinary ammonium excretion did not differ among groups. However, acid loading increased urinary ammonium excretion in all groups, but to a lesser extent in the O-GI group. SNAT3 mRNA expression was enhanced in both obese groups. PDG expression was elevated only in acid-loaded O-GI mice, whereas PEPCK was enhanced in both O-GI and NR groups given NH4CI. NHE activity in the brush border membrane of the proximal tubule was strongly reduced in the O-GI group whereas RhCG expression was similar. Conclusion: In sum, obesity and glucose intolerance impairs renal ammonium excretion in response to NH4CI feeding most likely through reduced NHE activity. The stimulation of SNAT3 and ammoniagenic enzyme expression may be compensatory but futile.

  13. Fructose Malabsorption and Intolerance: Effects of Fructose with and without Simultaneous Glucose Ingestion

    Science.gov (United States)

    Latulippe, Marie E.; Skoog, Suzanne M.

    2011-01-01

    Concern exists that increasing fructose consumption, particularly in the form of high-fructose corn syrup, is resulting in increasing rates of fructose intolerance and aggravation of clinical symptoms in individuals with irritable bowel syndrome. Most clinical trials designed to test this hypothesis have used pure fructose, a form not commonly found in the food supply, often in quantities and concentrations that exceed typical fructose intake levels. In addition, the amount of fructose provided in tests for malabsorption, which is thought to be a key cause of intolerance, often exceeds the normal physiological absorption capacity for this sugar. To help health professionals accurately identify and treat this condition, this article reviews clinical data related to understanding fructose malabsorption and intolerance (i.e., malabsorption that manifests with symptoms) relative to usual fructose and other carbohydrate intake. Because simultaneous consumption of glucose attenuates fructose malabsorption, information on the fructose and glucose content of foods, beverages, and ingredients representing a variety of food categories is provided. PMID:21793722

  14. Fructose malabsorption and intolerance: effects of fructose with and without simultaneous glucose ingestion.

    Science.gov (United States)

    Latulippe, Marie E; Skoog, Suzanne M

    2011-08-01

    Concern exists that increasing fructose consumption, particularly in the form of high-fructose corn syrup, is resulting in increasing rates of fructose intolerance and aggravation of clinical symptoms in individuals with irritable bowel syndrome. Most clinical trials designed to test this hypothesis have used pure fructose, a form not commonly found in the food supply, often in quantities and concentrations that exceed typical fructose intake levels. In addition, the amount of fructose provided in tests for malabsorption, which is thought to be a key cause of intolerance, often exceeds the normal physiological absorption capacity for this sugar. To help health professionals accurately identify and treat this condition, this article reviews clinical data related to understanding fructose malabsorption and intolerance (i.e., malabsorption that manifests with symptoms) relative to usual fructose and other carbohydrate intake. Because simultaneous consumption of glucose attenuates fructose malabsorption, information on the fructose and glucose content of foods, beverages, and ingredients representing a variety of food categories is provided.

  15. Ozone induces glucose intolerance and systemic metabolic effects in young and aged brown Norway rats

    Energy Technology Data Exchange (ETDEWEB)

    Bass, V. [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Gordon, C.J.; Jarema, K.A.; MacPhail, R.C. [Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Cascio, W.E. [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Phillips, P.M. [Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Ledbetter, A.D.; Schladweiler, M.C. [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Andrews, D. [Research Cores Unit, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Miller, D. [Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC (United States); Doerfler, D.L. [Research Cores Unit, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Kodavanti, U.P., E-mail: kodavanti.urmila@epa.gov [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States)

    2013-12-15

    Air pollutants have been associated with increased diabetes in humans. We hypothesized that ozone would impair glucose homeostasis by altering insulin signaling and/or endoplasmic reticular (ER) stress in young and aged rats. One, 4, 12, and 24 month old Brown Norway (BN) rats were exposed to air or ozone, 0.25 or 1.0 ppm, 6 h/day for 2 days (acute) or 2 d/week for 13 weeks (subchronic). Additionally, 4 month old rats were exposed to air or 1.0 ppm ozone, 6 h/day for 1 or 2 days (time-course). Glucose tolerance tests (GTT) were performed immediately after exposure. Serum and tissue biomarkers were analyzed 18 h after final ozone for acute and subchronic studies, and immediately after each day of exposure in the time-course study. Age-related glucose intolerance and increases in metabolic biomarkers were apparent at baseline. Acute ozone caused hyperglycemia and glucose intolerance in rats of all ages. Ozone-induced glucose intolerance was reduced in rats exposed for 13 weeks. Acute, but not subchronic ozone increased α{sub 2}-macroglobulin, adiponectin and osteopontin. Time-course analysis indicated glucose intolerance at days 1 and 2 (2 > 1), and a recovery 18 h post ozone. Leptin increased day 1 and epinephrine at all times after ozone. Ozone tended to decrease phosphorylated insulin receptor substrate-1 in liver and adipose tissues. ER stress appeared to be the consequence of ozone induced acute metabolic impairment since transcriptional markers of ER stress increased only after 2 days of ozone. In conclusion, acute ozone exposure induces marked systemic metabolic impairments in BN rats of all ages, likely through sympathetic stimulation. - Highlights: • Air pollutants have been associated with increased diabetes in humans. • Acute ozone exposure produces profound metabolic alterations in rats. • Age influences metabolic risk factors in aging BN rats. • Acute metabolic effects are reversible and repeated exposure reduces these effects. • Ozone

  16. Ozone induces glucose intolerance and systemic metabolic effects in young and aged brown Norway rats

    International Nuclear Information System (INIS)

    Bass, V.; Gordon, C.J.; Jarema, K.A.; MacPhail, R.C.; Cascio, W.E.; Phillips, P.M.; Ledbetter, A.D.; Schladweiler, M.C.; Andrews, D.; Miller, D.; Doerfler, D.L.; Kodavanti, U.P.

    2013-01-01

    Air pollutants have been associated with increased diabetes in humans. We hypothesized that ozone would impair glucose homeostasis by altering insulin signaling and/or endoplasmic reticular (ER) stress in young and aged rats. One, 4, 12, and 24 month old Brown Norway (BN) rats were exposed to air or ozone, 0.25 or 1.0 ppm, 6 h/day for 2 days (acute) or 2 d/week for 13 weeks (subchronic). Additionally, 4 month old rats were exposed to air or 1.0 ppm ozone, 6 h/day for 1 or 2 days (time-course). Glucose tolerance tests (GTT) were performed immediately after exposure. Serum and tissue biomarkers were analyzed 18 h after final ozone for acute and subchronic studies, and immediately after each day of exposure in the time-course study. Age-related glucose intolerance and increases in metabolic biomarkers were apparent at baseline. Acute ozone caused hyperglycemia and glucose intolerance in rats of all ages. Ozone-induced glucose intolerance was reduced in rats exposed for 13 weeks. Acute, but not subchronic ozone increased α 2 -macroglobulin, adiponectin and osteopontin. Time-course analysis indicated glucose intolerance at days 1 and 2 (2 > 1), and a recovery 18 h post ozone. Leptin increased day 1 and epinephrine at all times after ozone. Ozone tended to decrease phosphorylated insulin receptor substrate-1 in liver and adipose tissues. ER stress appeared to be the consequence of ozone induced acute metabolic impairment since transcriptional markers of ER stress increased only after 2 days of ozone. In conclusion, acute ozone exposure induces marked systemic metabolic impairments in BN rats of all ages, likely through sympathetic stimulation. - Highlights: • Air pollutants have been associated with increased diabetes in humans. • Acute ozone exposure produces profound metabolic alterations in rats. • Age influences metabolic risk factors in aging BN rats. • Acute metabolic effects are reversible and repeated exposure reduces these effects. • Ozone metabolic

  17. Frequency of diabetes, impaired fasting glucose, and glucose intolerance in high-risk groups identified by a FINDRISC survey in Puebla City, Mexico.

    Science.gov (United States)

    García-Alcalá, Hector; Genestier-Tamborero, Christelle Nathalie; Hirales-Tamez, Omara; Salinas-Palma, Jorge; Soto-Vega, Elena

    2012-01-01

    As a first step in the prevention of diabetes, the International Diabetes Federation recommends identification of persons at risk using the Finnish type 2 Diabetes Risk Assessment (FINDRISC) survey. The frequency of diabetes mellitus, impaired fasting glucose, and glucose intolerance in high-risk groups identified by FINDRISC is unknown in our country. The aim of this study was to determine the frequency of diabetes mellitus, impaired fasting glucose, and glucose intolerance in higher-risk groups using a FINDRISC survey in an urban population. We used a television program to invite interested adults to fill out a survey at a television station. An oral glucose tolerance test was performed in all persons with a FINDRISC score ≥ 15 points (high-risk and very high-risk groups). Patients were classified as normal (fasting glucose < 100 mg/dL and 2-hour glucose < 140 mg/dL), or having impaired fasting glucose (fasting glucose 100-125 mg/dL and 2-hour glucose < 140 mg/dL), glucose intolerance (fasting glucose < 126 mg/dL and 2-hour glucose 140-199 mg/dL), and diabetes mellitus (fasting glucose ≥ 126 mg/dL or 2-hour glucose ≥ 200 mg/dL). We describe the frequency of each diagnostic category in this selected population according to gender and age. A total of 186 patients had a score ≥ 15. The frequencies of diabetes mellitus, impaired fasting glucose, glucose intolerance, and normal glucose levels were 28.6%, 25.9%, 29.2%, and 16.2%, respectively. We found a higher frequency of diabetes mellitus and impaired fasting glucose in men than in women (33% versus 27% and 40% versus 21%, respectively) and more glucose intolerance in women than in men (34% versus 16%, P < 0.05). Patients with diabetes mellitus (52.55 ± 9.2 years) were older than those with impaired fasting glucose (46.19 ± 8.89 years), glucose intolerance (46.15 ± 10.9 years), and normal levels (41.9 ± 10.45 years, P < 0.05). We found a higher frequency of diabetes mellitus in those aged over 50 years

  18. High fat diet-induced glucose intolerance impairs myocardial function, but not myocardial perfusion during hyperaemia: a pilot study

    Directory of Open Access Journals (Sweden)

    van den Brom Charissa E

    2012-06-01

    Full Text Available Abstract Background Glucose intolerance is a major health problem and is associated with increased risk of progression to type 2 diabetes mellitus and cardiovascular disease. However, whether glucose intolerance is related to impaired myocardial perfusion is not known. The purpose of the present study was to study the effect of diet-induced glucose intolerance on myocardial function and perfusion during baseline and pharmacological induced hyperaemia. Methods Male Wistar rats were randomly exposed to a high fat diet (HFD or control diet (CD (n = 8 per group. After 4 weeks, rats underwent an oral glucose tolerance test. Subsequently, rats underwent (contrast echocardiography to determine myocardial function and perfusion during baseline and dipyridamole-induced hyperaemia (20 mg/kg for 10 min. Results Four weeks of HFD feeding resulted in glucose intolerance compared to CD-feeding. Contractile function as represented by fractional shortening was not altered in HFD-fed rats compared to CD-fed rats under baseline conditions. However, dipyridamole increased fractional shortening in CD-fed rats, but not in HFD-fed rats. Basal myocardial perfusion, as measured by estimate of perfusion, was similar in CD- and HFD-fed rats, whereas dipyridamole increased estimate of perfusion in CD-fed rats, but not in HFD-fed rats. However, flow reserve was not different between CD- and HFD-fed rats. Conclusions Diet-induced glucose intolerance is associated with impaired myocardial function during conditions of hyperaemia, but myocardial perfusion is maintained. These findings may result in new insights into the effect of glucose intolerance on myocardial function and perfusion during hyperaemia.

  19. Microflora Disturbance during Progression of Glucose Intolerance and Effect of Sitagliptin: An Animal Study

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    Xinfeng Yan

    2016-01-01

    Full Text Available Background. Emerging evidences have shown a close interplay between obesity, diabetes, and intestinal flora disturbance. Dipeptidyl peptidase-4 inhibitor, exemplified by sitagliptin, is highly efficacious in treating type 2 diabetes (T2DM, yet little is known if sitagliptin exerts beneficial effects on microbiota associated with obesity and T2DM. We evaluated changes of gut microbiota following the induction of obesity and T2DM in a streptozotocin treated high fat/high carbohydrate fed (HF/HC-STZ rat model and explored the effect of sitagliptin on gut microbiota for HF/HC-STZ rats. Methods. Sitagliptin was administered via oral gavage to diabetic rats. Fecal DNA extraction and 454 pyrosequencing based on analysis of 16S rRNA genes was utilized to determine the overall structure of microbiota in fecal DNA samples. Results. Results showed that, at the level of phylum, there was higher abundance of Firmicutes and Tenericutes and less abundance of Bacteroidetes in obese rats compared to their lean counterparts. At the level of genus, short-chain fatty acid- (SCFA- producing bacteria, Blautia, Roseburia, and Clostridium, and probiotics Lactobacillus, Bifidobacterium, and so forth were identified significantly different from each other among conditions. Conclusion. Marked shifts of the gut microbiota structure were observed in the rats during development of glucose intolerance. Intestinal flora changed in the process of glucose intolerance, and treatment of sitagliptin moderately corrected the dysbiosis of microbiota in T2DM.

  20. High protein and cholesterol intakes associated with emergence of glucose intolerance in a low-risk Canadian Inuit population.

    Science.gov (United States)

    Sefidbakht, Saghar; Johnson-Down, Louise; Young, T Kue; Egeland, Grace M

    2016-07-01

    The rate of type 2 diabetes mellitus among Inuit is 12·2 % in individuals over 50 years of age, similar to the Canadian prevalence. Given marked dietary transitions in the Arctic, we evaluated the dietary and other correlates of not previously diagnosed glucose intolerance, defined as type 2 diabetes mellitus, impaired fasting glucose or impaired glucose tolerance. Cross-sectional analyses were limited to adults with a completed 2 h oral glucose tolerance test and without pre-existing diabetes. Anthropometric assessments, health and medication usage questionnaires and a 24 h dietary recall were administered. Canadian International Polar Year Inuit Health Survey (2007-2008). Inuit adults (n 777). Glucose intolerance was associated with older age and adiposity. Percentage of energy from protein above the Acceptable Macronutrient Distribution Range of 35 %, compared with intake within the range, was associated with increased odds of glucose intolerance (OR=1·98; 95 % CI 1·09, 3·61) in multivariable analyses. Further, cholesterol intake in the highest three quartiles combined (median exposures of 207, 416 and 778 mg/d, respectively) compared with the lowest quartile (median intake of 81 mg/d) was associated with glucose intolerance (OR=2·15; 95 % CI 1·23, 3·78) in multivariable analyses. Past-day traditional food consumption was borderline protective of glucose intolerance (P=0·054) and high fibre intake was not significantly protective (P=0·08). The results contribute to the existing literature on high protein and cholesterol intakes as they may relate to diabetes risk.

  1. Association of leukocyte count with varying degrees of glucose intolerance in Asian Indians: the Chennai Urban Rural Epidemiology Study (CURES-26).

    Science.gov (United States)

    Gokulakrishnan, Kuppan; Deepa, Raj; Sampathkumar, Rangasamy; Balasubramanyam, Muthuswamy; Mohan, Viswanathan

    2009-06-01

    This study assessed the association of leukocyte count with different grades of glucose intolerance in Asian Indian subjects. Three groups of subjects were recruited from the Chennai Urban Rural Epidemiology Study (CURES), a population-based study, representative of Chennai (formerly Madras), a city in southern India. Group 1 represented normal glucose tolerance (NGT) (n = 840), group 2 included impaired glucose tolerance (IGT) (n = 180), and group 3 included type 2 diabetes (n = 1170). Anthropometric measurements including weight, height, and waist measurements were obtained using standardized techniques. Leukocyte count was measured by an automated flow cytometry instrument (Sysmex SF-3000, Japan). Fasting insulin was measured by enzyme-linked immunosorbent assay and insulin resistance was calculated using the homeostasis model assessment (HOMA-IR). Subjects with diabetes (8.0 +/- 1.5 x 10(3)/microL) and IGT (7.9 +/- 1.3 x 10(3)/microL) had a significantly higher mean leukocyte count compared to the NGT group (7.4 +/- 1.5 x 10(3)/microL) (P Leukocyte count was significantly increased in NGT subjects with insulin resistance (IR) as measured by HOMA-IR (7.5 +/- 1.5 x 10(3)/microL; P leukocyte count with increasing severity of glucose intolerance, even after adjusting for age, waist circumference, and HOMA-IR. Among Asian Indians who are known to have high risk of premature coronary artery disease and diabetes, a significant association exists between leukocyte count and glucose intolerance.

  2. Dietary α-lactalbumin supplementation alleviates normocaloric western diet-induced glucose intolerance in Göttingen minipigs.

    Science.gov (United States)

    Blat, Sophie; Vincent, Sophie; Lefeuvre, Luz; Lemoine-Morel, Sophie; Malbert, Charles-Henri; Pichon, Lisa; Mikogami, Takashi; Gratas-Delamarche, Arlette

    2015-02-01

    The pandemic of obesity in Western countries is mainly due to the high-fat, high-energy diet prevailing there. Obesity-associated metabolic disorders are the consequence of fat mass increase leading to altered adipokine secretion, hyperlipemia, oxidant stress, low-grade inflammation, and eventually glucose intolerance. Yet not all people consuming a Western diet become obese, and the question is raised whether these people are also at risk of developing metabolic disorders. Glucose tolerance, lipid profile, and oxidant and inflammation status were investigated longitudinally in lean Göttingen minipigs receiving for 16 weeks either a normal diet (ND), a Western diet (WD), or a Western diet supplemented with a whey protein isolate (WPI) rich in α-lactalbumin known to improve glucose tolerance. ND and WD were supplied isoenergetically. Lean minipigs fed WD displayed glucose intolerance and altered lipid profile after 6 weeks of diet but no inflammation or oxidative stress. Supplementation with WPI alleviated glucose intolerance by improving insulin secretion, but not lipid profile. Western diet consumption is deleterious for glucose tolerance even in the absence of fat mass accretion, and dyslipemia is a major determinant for this metabolic dysfunction. Stimulating insulin secretion with a WPI is an effective strategy to improve glucose tolerance. © 2014 The Obesity Society.

  3. Insulin receptor isoform A ameliorates long-term glucose intolerance in diabetic mice

    Science.gov (United States)

    Diaz-Castroverde, Sabela; Gómez-Hernández, Almudena; Fernández, Silvia; García-Gómez, Gema; Di Scala, Marianna; González-Aseguinolaza, Gloria; Fernández-Millán, Elisa; González-Rodríguez, Águeda; García-Bravo, María; Chambon, Pierre; Álvarez, Carmen; Perdomo, Liliana; Beneit, Nuria; Benito, Manuel

    2016-01-01

    ABSTRACT Type 2 diabetes mellitus is a complex metabolic disease and its pathogenesis involves abnormalities in both peripheral insulin action and insulin secretion. Previous in vitro data showed that insulin receptor isoform A, but not B, favours basal glucose uptake through its specific association with endogenous GLUT1/2 in murine hepatocytes and beta cells. With this background, we hypothesized that hepatic expression of insulin receptor isoform A in a mouse model of type 2 diabetes could potentially increase the glucose uptake of these cells, decreasing the hyperglycaemia and therefore ameliorating the diabetic phenotype. To assure this hypothesis, we have developed recombinant adeno-associated viral vectors expressing insulin receptor isoform A (IRA) or isoform B (IRB) under the control of a hepatocyte­-specific promoter. Our results demonstrate that in the long term, hepatic expression of IRA in diabetic mice is more efficient than IRB in ameliorating glucose intolerance. Consequently, it impairs the induction of compensatory mechanisms through beta cell hyperplasia and/or hypertrophy that finally lead to beta cell failure, reverting the diabetic phenotype in about 8 weeks. Our data suggest that long-term hepatic expression of IRA could be a promising therapeutic approach for the treatment of type 2 diabetes mellitus. PMID:27562101

  4. Long-term ketogenic diet causes glucose intolerance and reduced β- and α-cell mass but no weight loss in mice.

    Science.gov (United States)

    Ellenbroek, Johanne H; van Dijck, Laura; Töns, Hendrica A; Rabelink, Ton J; Carlotti, Françoise; Ballieux, Bart E P B; de Koning, Eelco J P

    2014-03-01

    High-fat, low-carbohydrate ketogenic diets (KD) are used for weight loss and for treatment of refractory epilepsy. Recently, short-time studies in rodents have shown that, besides their beneficial effect on body weight, KD lead to glucose intolerance and insulin resistance. However, the long-term effects on pancreatic endocrine cells are unknown. In this study we investigate the effects of long-term KD on glucose tolerance and β- and α-cell mass in mice. Despite an initial weight loss, KD did not result in weight loss after 22 wk. Plasma markers associated with dyslipidemia and inflammation (cholesterol, triglycerides, leptin, monocyte chemotactic protein-1, IL-1β, and IL-6) were increased, and KD-fed mice showed signs of hepatic steatosis after 22 wk of diet. Long-term KD resulted in glucose intolerance that was associated with insufficient insulin secretion from β-cells. After 22 wk, insulin-stimulated glucose uptake was reduced. A reduction in β-cell mass was observed in KD-fed mice together with an increased number of smaller islets. Also α-cell mass was markedly decreased, resulting in a lower α- to β-cell ratio. Our data show that long-term KD causes dyslipidemia, a proinflammatory state, signs of hepatic steatosis, glucose intolerance, and a reduction in β- and α-cell mass, but no weight loss. This indicates that long-term high-fat, low-carbohydrate KD lead to features that are also associated with the metabolic syndrome and an increased risk for type 2 diabetes in humans.

  5. Sympathetic overactivity precedes metabolic dysfunction in a fructose model of glucose intolerance in mice

    Science.gov (United States)

    Angelis, Katia De; Senador, Danielle D.; Mostarda, Cristiano; Irigoyen, Maria C.

    2012-01-01

    Consumption of high levels of fructose in humans and animals leads to metabolic and cardiovascular dysfunction. There are questions as to the role of the autonomic changes in the time course of fructose-induced dysfunction. C57/BL male mice were given tap water or fructose water (100 g/l) to drink for up to 2 mo. Groups were control (C), 15-day fructose (F15), and 60-day fructose (F60). Light-dark patterns of arterial pressure (AP) and heart rate (HR), and their respective variabilities were measured. Plasma glucose, lipids, insulin, leptin, resistin, adiponectin, and glucose tolerance were quantified. Fructose increased systolic AP (SAP) at 15 and 60 days during both light (F15: 123 ± 2 and F60: 118 ± 2 mmHg) and dark periods (F15: 136 ± 4 and F60: 136 ± 5 mmHg) compared with controls (light: 111 ± 2 and dark: 117 ± 2 mmHg). SAP variance (VAR) and the low-frequency component (LF) were increased in F15 (>60% and >80%) and F60 (>170% and >140%) compared with C. Cardiac sympatho-vagal balance was enhanced, while baroreflex function was attenuated in fructose groups. Metabolic parameters were unchanged in F15. However, F60 showed significant increases in plasma glucose (26%), cholesterol (44%), triglycerides (22%), insulin (95%), and leptin (63%), as well as glucose intolerance. LF of SAP was positively correlated with SAP. Plasma leptin was correlated with triglycerides, insulin, and glucose tolerance. Results show that increased sympathetic modulation of vessels and heart preceded metabolic dysfunction in fructose-consuming mice. Data suggest that changes in autonomic modulation may be an initiating mechanism underlying the cluster of symptoms associated with cardiometabolic disease. PMID:22319048

  6. The "metabolic syndrome" is less useful than random plasma glucose to screen for glucose intolerance.

    Science.gov (United States)

    El Bassuoni, Eman A; Ziemer, David C; Kolm, Paul; Rhee, Mary K; Vaccarino, Viola; Tsui, Circe W; Kaufman, Jack M; Osinski, G Eileen; Koch, David D; Narayan, K M Venkat; Weintraub, William S; Phillips, Lawrence S

    2008-09-01

    To compare the utility of metabolic syndrome (MetS) to random plasma glucose (RPG) in identifying people with diabetes or prediabetes. RPG was measured and an OGTT was performed in 1155 adults. Test performance was measured by area under the receiver-operating-characteristic curve (AROC). Diabetes was found in 5.1% and prediabetes in 20.0%. AROC for MetS with fasting plasma glucose (FPG) was 0.80 to detect diabetes, and 0.76 for diabetes or prediabetes--similar to RPG alone (0.82 and 0.72). However, the AROC for MetS excluding fasting plasma glucose was lower: 0.69 for diabetes (pRPG and MetS with FPG), and 0.69 for diabetes or prediabetes. AROCs for MetS with FPG and RPG were comparable and higher for recognizing diabetes in blacks vs. whites, and females vs. males. MetS with FPG was superior to RPG for identifying diabetes only in subjects with age RPG--a more convenient and less expensive test.

  7. Carbenoxolone treatment ameliorated metabolic syndrome in WNIN/Ob obese rats, but induced severe fat loss and glucose intolerance in lean rats.

    Directory of Open Access Journals (Sweden)

    Siva Sankara Vara Prasad Sakamuri

    Full Text Available BACKGROUND: 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1 regulates local glucocorticoid action in tissues by catalysing conversion of inactive glucocorticoids to active glucocorticoids. 11β-HSD1 inhibition ameliorates obesity and associated co-morbidities. Here, we tested the effect of 11β-HSD inhibitor, carbenoxolone (CBX on obesity and associated comorbidities in obese rats of WNIN/Ob strain, a new animal model for genetic obesity. METHODOLOGY/PRINCIPAL FINDINGS: Subcutaneous injection of CBX (50 mg/kg body weight or volume-matched vehicle was given once daily for four weeks to three month-old WNIN/Ob lean and obese rats (n = 6 for each phenotype and for each treatment. Body composition, plasma lipids and hormones were assayed. Hepatic steatosis, adipose tissue morphology, inflammation and fibrosis were also studied. Insulin resistance and glucose intolerance were determined along with tissue glycogen content. Gene expressions were determined in liver and adipose tissue. CBX significantly inhibited 11β-HSD1 activity in liver and adipose tissue of WNIN/Ob lean and obese rats. CBX significantly decreased body fat percentage, hypertriglyceridemia, hypercholesterolemia, insulin resistance in obese rats. CBX ameliorated hepatic steatosis, adipocyte hypertrophy, adipose tissue inflammation and fibrosis in obese rats. Tissue glycogen content was significantly decreased by CBX in liver and adipose tissue of obese rats. Severe fat loss and glucose- intolerance were observed in lean rats after CBX treatment. CONCLUSIONS/SIGNIFICANCE: We conclude that 11β-HSD1 inhibition by CBX decreases obesity and associated co-morbidities in WNIN/Ob obese rats. Our study supports the hypothesis that inhibition of 11β-HSD1 is a key strategy to treat metabolic syndrome. Severe fat loss and glucose -intolerance by CBX treatment in lean rats suggest that chronic 11β-HSD1 inhibition may lead to insulin resistance in normal conditions.

  8. Changes in hippocampal synaptic functions and protein expression in monosodium glutamate-treated obese mice during development of glucose intolerance.

    Science.gov (United States)

    Sasaki-Hamada, Sachie; Hojo, Yuki; Koyama, Hajime; Otsuka, Hayuma; Oka, Jun-Ichiro

    2015-05-01

    Glucose is the sole neural fuel for the brain and is essential for cognitive function. Abnormalities in glucose tolerance may be associated with impairments in cognitive function. Experimental obese model mice can be generated by an intraperitoneal injection of monosodium glutamate (MSG; 2 mg/g) once a day for 5 days from 1 day after birth. MSG-treated mice have been shown to develop glucose intolerance and exhibit chronic neuroendocrine dysfunction associated with marked cognitive malfunctions at 28-29  weeks old. Although hippocampal synaptic plasticity is impaired in MSG-treated mice, changes in synaptic transmission remain unknown. Here, we investigated whether glucose intolerance influenced cognitive function, synaptic properties and protein expression in the hippocampus. We demonstrated that MSG-treated mice developed glucose intolerance due to an impairment in the effectiveness of insulin actions, and showed cognitive impairments in the Y-maze test. Moreover, long-term potentiation (LTP) at Schaffer collateral-CA1 pyramidal synapses in hippocampal slices was impaired, and the relationship between the slope of extracellular field excitatory postsynaptic potential and stimulus intensity of synaptic transmission was weaker in MSG-treated mice. The protein levels of vesicular glutamate transporter 1 and GluA1 glutamate receptor subunits decreased in the CA1 region of MSG-treated mice. These results suggest that deficits in glutamatergic presynapses as well as postsynapses lead to impaired synaptic plasticity in MSG-treated mice during the development of glucose intolerance, though it remains unknown whether impaired LTP is due to altered inhibitory transmission. It may be important to examine changes in glucose tolerance in order to prevent cognitive malfunctions associated with diabetes. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  9. Fermented Moringa oleifera Decreases Hepatic Adiposity and Ameliorates Glucose Intolerance in High-Fat Diet-Induced Obese Mice.

    Science.gov (United States)

    Joung, Hyunchae; Kim, Bobae; Park, Hyunjoon; Lee, Kyuyeon; Kim, Hee-Hoon; Sim, Ho-Cheol; Do, Hyun-Jin; Hyun, Chang-Kee; Do, Myoung-Sool

    2017-05-01

    Metabolic diseases, such as glucose intolerance and nonalcoholic fatty-liver disease (NAFLD), are primary risk factors for life-threatening conditions such as diabetes, heart attack, stroke, and hepatic cancer. Extracts from the tropical tree Moringa oleifera show antidiabetic, antioxidant, anti-inflammatory, and anticancer effects. Fermentation can further improve the safety and nutritional value of certain foods. We investigated the efficacy of fermented M. oleifera extract (FM) against high-fat diet (HFD)-induced glucose intolerance and hepatic lipid accumulation and investigated the underlying mechanisms by analyzing expression of proteins and genes involved in glucose and lipid regulation. C57BL/6 mice were fed with normal chow diet (ND) or HFD supplemented with distilled water (DW, control), nonfermented M. oleifera extract (NFM), or FM for 10 weeks. Although body weights were similar among HFD-fed treatment groups, liver weight was decreased, and glucose tolerance test (GTT) results improved in the FM group compared with DW and NFM groups. Hepatic lipid accumulation was also lower in the FM group, and expressions of genes involved in liver lipid metabolism were upregulated. In addition, HFD-induced endoplasmic reticulum (ER) stress, oxidative stress, and lipotoxicity in quadriceps muscles were decreased by FM. Finally, proinflammatory cytokine mRNA expression was decreased by FM in the liver, epididymal adipose tissue, and quadriceps of HFD-fed mice. FMs may decrease glucose intolerance and NAFLD under HFD-induced obesity by decreasing ER stress, oxidative stress, and inflammation.

  10. Catch-up growth following food restriction exacerbates adulthood glucose intolerance in pigs exposed to intrauterine undernutrition.

    Science.gov (United States)

    Wang, Jun; Cao, Meng; Zhuo, Yong; Che, Lianqiang; Fang, Zhengfeng; Xu, Shengyu; Lin, Yan; Feng, Bin; Wu, De

    2016-01-01

    The aim of this study was to evaluate the effects of food restriction followed by controlled refeeding on glucose tolerance in pigs exposed to intrauterine malnutrition. Pregnant sows (n = 11) were assigned to either a control (C) group or an undernutrition (U) group (75% of C) during gestation. At postnatal 68 d, the offspring (n = 16) were placed on either a cafeteria feeding (CF) group or a food-restricted (FR) group (75% of CF) for 6 wk. After that, all offspring were fed ad libitum until 189 d (dpn189). The results showed that maternal malnutrition induced offspring glucose intolerance, which was demonstrated by increased serum glucose and triacylglycerol content at dpn189, as well as increased area under the blood glucose curve (AUC) during the intravenous glucose tolerance test (i.v.GTT) (P food restriction followed by controlled refeeding further increased serum glucose content at dpn189 and AUC during i.v.GTT in pigs born from U sows (P food restriction can exacerbate glucose intolerance in offspring exposed to intrauterine malnutrition. This may be caused by increased hepatic gluconeogenesis, decreased muscle glucose transport, and impaired hepatic insulin signaling. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Hepatic rather than cardiac steatosis relates to glucose intolerance in women with prior gestational diabetes.

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    Yvonne Winhofer

    Full Text Available BACKGROUND: Increased myocardial lipid accumulation has been described in patients with pre- and overt type 2 diabetes and could underlie the development of left-ventricular dysfunction in metabolic diseases (diabetic cardiomyopathy. Since women with prior gestational diabetes (pGDM display a generally young population at high risk of developing diabetes and associated cardiovascular complications, we aimed to assess whether myocardial lipid accumulation can be detected at early stages of glucose intolerance and relates to markers of hepatic steatosis (Fatty Liver Index, cardiac function, insulin sensitivity and secretion. METHODS: Myocardial lipid content (MYCL, left-ventricular function (1H-magnetic-resonance-spectroscopy and -imaging, insulin sensitivity/secretion (oral glucose tolerance test and the fatty liver index (FLI were assessed in 35 pGDM (45.6±7.0 years, 28.3±4.8 kg/m2 and 14 healthy control females (CON; 44.7±9.8 years, 26.1±2.5 kg/m2, matching for age and body-mass-index (each p>0.1. RESULTS: Of 35 pGDM, 9 displayed normal glucose tolerance (NGT, 6 impaired glucose regulation (IGR and 20 had been already diagnosed with type 2 diabetes (T2DM. MYCL and cardiac function were comparable between pGDM and CON; in addition, no evidence of left-ventricular dysfunction was observed. MYCL was inversely correlated with the ejection fraction in T2DM (R = -0.45, p<0.05, while the FLI was tightly correlated with metabolic parameters (such as HbA1C, fasting plasma glucose and HDL-cholesterol and rose along GT-groups. CONCLUSIONS: There is no evidence of cardiac steatosis in middle-aged women with prior gestational diabetes, suggesting that cardiac complications might develop later in the time-course of diabetes and may be accelerated by the co-existence of further risk factors, whereas hepatic steatosis remains a valid biomarker for metabolic diseases even in this rather young female cohort.

  12. The Root of Atractylodes macrocephala Koidzumi Prevents Obesity and Glucose Intolerance and Increases Energy Metabolism in Mice

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    Mi Young Song

    2018-01-01

    Full Text Available Targeting energy expenditure offers a strategy for treating obesity more effectively and safely. In previous studies, we found that the root of Atractylodes macrocephala Koidzumi (Atractylodis Rhizoma Alba, ARA increased energy metabolism in C2C12 cells. Here, we investigated the effects of ARA on obesity and glucose intolerance by examining energy metabolism in skeletal muscle and brown fat in high-fat diet (HFD induced obese mice. ARA decreased body weight gain, hepatic lipid levels and serum total cholesterol levels, but did not modify food intake. Fasting serum glucose, serum insulin levels and glucose intolerance were all improved in ARA treated mice. Furthermore, ARA increased peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α expression, and the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK in skeletal muscle tissues, and also prevented skeletal muscle atrophy. In addition, the numbers of brown adipocytes and the expressions of PGC1α and uncoupling protein 1 (UCP1 were elevated in the brown adipose tissues of ARA treated mice. Our results show that ARA can prevent diet-induced obesity and glucose intolerance in C5BL/6 mice and suggests that the mechanism responsible is related to the promotion of energy metabolism in skeletal muscle and brown adipose tissues.

  13. Loss of Nlrp3 Does Not Protect Mice from Western Diet-Induced Adipose Tissue Inflammation and Glucose Intolerance.

    Science.gov (United States)

    Ringling, Rebecca E; Gastecki, Michelle L; Woodford, Makenzie L; Lum-Naihe, Kelly J; Grant, Ryan W; Pulakat, Lakshmi; Vieira-Potter, Victoria J; Padilla, Jaume

    2016-01-01

    We tested the hypothesis that loss of Nlrp3 would protect mice from Western diet-induced adipose tissue (AT) inflammation and associated glucose intolerance and cardiovascular complications. Five-week old C57BL6J wild-type (WT) and Nlrp3 knockout (Nlrp3-/-) mice were randomized to either a control diet (10% kcal from fat) or Western diet (45% kcal from fat and 1% cholesterol) for 24 weeks (n = 8/group). Contrary to our hypothesis that obesity-mediated white AT inflammation is Nlrp3-dependent, we found that Western diet-induced expression of AT inflammatory markers (i.e., Cd68, Cd11c, Emr1, Itgam, Lgals, Il18, Mcp1, Tnf, Ccr2, Ccl5 mRNAs, and Mac-2 protein) were not accompanied by increased caspase-1 cleavage, a hallmark feature of NLRP3 inflammasome activation. Furthermore, Nlrp3 null mice were not protected from Western diet-induced white or brown AT inflammation. Although Western diet promoted glucose intolerance in both WT and Nlrp3-/- mice, Nlrp3-/- mice were protected from Western diet-induced aortic stiffening. Additionally, Nlrp3-/- mice exhibited smaller cardiomyocytes and reduced cardiac fibrosis, independent of diet. Collectively, these findings suggest that presence of the Nlrp3 gene is not required for Western diet-induced AT inflammation and/or glucose intolerance; yet Nlrp3 appears to play a role in potentiating arterial stiffening, cardiac hypertrophy and fibrosis.

  14. CORRELATION BETWEEN GUT MICROBIOTA AND DEVELOPMENT OF GLUCOSE INTOLERANCE IN B6.V-Lepob/J LEPTIN DEFICIENT MICE

    DEFF Research Database (Denmark)

    Ellekilde, Merete; Hansen, Camilla Hartmann Friis; Nielsen, Dennis Sandris

    Life style associated diseases such as type 1 and 2 diabetes mellitus, atherosclerosis and inflammatory bowel disease originate form an adaptive immune response, which can be down regulated by a regulatory immune response and are under heavy stimulation from early life gut microbiota (GM). Today...... correlation was found between blood glucose, HbA1c% and glucose intolerance and the pro-inflammatory cytokine IL-12, supporting the correlation found between gut and disease, as IL-12 is secreted after microbial stimulation of immunological cells – e.g. In the gut. Further investigations concerning...

  15. Use of mycophenolate mofetil in patients with severe localized scleroderma resistant or intolerant to methotrexate

    NARCIS (Netherlands)

    Mertens, Jorre S.; Marsman, Diane; van de Kerkhof, Peter C M; Hoppenreijs, Esther P A H; Knaapen, Hanneke K A; Radstake, Timothy R D; de Jong, Elke M G J; Seyger, Marieke M B

    2016-01-01

    To assess the efficacy and safety of mycophenolate mofetil (MMF) in patients with localized scleroderma (LoS) resistant or intolerant to previous treatment with methotrexate (MTX). A case series of patients with LoS treated with MMF. Outcome was assessed through clinical examination. Adverse events

  16. A low socio-economic status is an additional risk factor for glucose intolerance in high risk Hong Kong Chinese

    International Nuclear Information System (INIS)

    Ko, Gary T.C.; Chan, Juliana C.N.; Yeung, Vincent T.F.; Chow, Chun-Chung; Tsang, Lynn W.W.; Cockram, Clive S.

    2001-01-01

    To examine whether a low socio-economic status (SES) is an additional risk factor for glucose intolerance in Hong Kong Chinese with known risk factors for glucose intolerance, a total of 2847 Chinese subjects (473 men and 2374 women) were recruited from the community for assessment. They had known risk factors for glucose intolerance including a previous history of gestational diabetes, positive family history of diabetes in first degree relatives and equivocal fasting plasma glucose concentrations between 7 and 8 mmol/l or random plasma glucose concentrations between 8 and 11 mmol/l. The 2847 subjects were classified according to their education levels and occupations: education group 1 = high school or university, group 2 = middle school, group 3 = illiterate or up to elementary school; occupational group 1 = professional or managerial, group 2 = non-manual, group 3 = manual, group 4 = unskilled, group 5 = housewife or unemployed. Different socio-economic groups were well represented in this selected population. The distribution of educational groups in this study was similar to that recorded in the 1991 Hong Kong Census. When analysed according to education levels and after adjustment for age, women in the lowest social class had the highest prevalence of diabetes, body mass index, blood pressure and plasma glucose concentrations. Men with the lowest education level had the highest prevalence of diabetes after age adjustment. The age-adjusted odds ratio (95% confidence intervals) of having diabetes was 2.3 (1.3, 4.3) in female subjects and 2.5 (1.2, 5.4) in male subjects with the lowest SES compared to subjects with the highest SES. When categorised according to occupation and after adjustment for age, women in the lowest social class had the highest prevalence of diabetes and glycaemic indexes. The age-adjusted odds ratio of having diabetes was 4.5 (1.9, 10.9) in female subjects with the lowest SES compared to those with the highest SES. The corresponding age

  17. [The importance of oral glucose tolerance test in diagnosis of glucose intolerance and type 2 diabetes mellitus in women with polycystic ovary syndrome].

    Science.gov (United States)

    Pontes, Ana Gabriela; Rehme, Marta Francis Benevides; Micussi, Maria Thereza Albuquerque Barbosa Cabral; Maranhão, Técia Maria de Oliveira; Pimenta, Walkyria de Paula; Carvalho, Lídia Raquel de; Pontes, Anaglória

    2012-03-01

    To evaluate the importance of the oral glucose tolerance test for the diagnosis of glucose intolerance (GI) and type 2 diabetes mellitus (DM-2) in women with PCOS. A retrospective study was conducted on 247 patients with PCOS selected at random. The diagnosis of GI was obtained from the two-hour oral glucose tolerance test with 75 g of glucose according to the criteria of the World Health Organization (WHO) (GI: 120 minutes for plasma glucose >140 mg/dL and 200 mg/dL) and fasting glucose using the criteria of the American Diabetes Association (impaired fasting glucose: fasting plasma glucose >100 and 126 mg/dL). A logistic regression model for repeated measures was applied to compare the oral glucose tolerance test with fasting plasma glucose. ANOVA followed by the Tukey test was used for the analysis of the clinical and biochemical characteristics of patients with and without GI and/or DM-2. A p<0.05 was considered statistically significant. PCOS patients had a mean age of 24.8±6.3, and body mass index (BMI) of 18.3 to 54.9 kg/m² (32.5±7.6). The percentage of obese patients was 64%, the percentage of overweight patients was 18.6% and 17.4% had healthy weight. The oral glucose tolerance test identified 14 cases of DM-2 (5.7%), while fasting glucose detected only three cases (1.2%), and the frequency of these disorders was higher with increasing age and BMI. The results of this study demonstrate the superiority of the oral glucose tolerance test in relation to fasting glucose in diagnosing DM-2 in young women with PCOS and should be performed in these patients.

  18. Interaction of BDNF rs6265 variants and energy and protein intake in the risk for glucose intolerance and type 2 diabetes in middle-aged adults.

    Science.gov (United States)

    Daily, James W; Park, Sunmin

    2017-01-01

    Brain-derived neurotrophic factor (BDNF) is associated with the risk for Alzheimer's disease and type 2 diabetes. The aim of this study was to examine the association of BDNF variants with type 2 diabetes and the interactions of different BDNF genotypes with dietary habits and food and nutrient intakes in middle-aged adults. The study population included 8840 adults ages 40 to 65 y from the Ansan and Asung areas in the Korean Genome Epidemiology Study, a cross-sectional study of Korean adults, conducted from 2001 to 2002. Adjusted odd ratios for the prevalence of glucose intolerance and type 2 diabetes according to BDNF genotypes were calculated after adjusting for age, sex, residence area, body mass index, physical activity, and smoking and stress status. Nutrient intake was calculated from usual food intake determined by semiquantitative food frequencies using the nutrient assessment software. BDNF rs6265 Val/Met and Met/Met variants were negatively associated with the risk for type 2 diabetes after adjusting for covariates. Serum glucose levels after glucose loading and hemoglobin A1c, but not serum insulin levels, also were negatively associated with BDNF Val/Met and Met/Met. In subgroup analysis, sex and stress levels had an interaction with BDNF Val/Met in the risk for type 2 diabetes. Glucose-intolerant and diabetic, but not nondiabetic, patients with BDNF Met/Met had nominally, but significantly higher intakes of energy than those with BDNF Val/Val. BDNF rs6265 had consistent gene-diet interactions with energy and protein intake. With low-energy, low-protein, and high-carbohydrate intake, BDNF Val/Met lowered the risk for type 2 diabetes after adjusting for confounding factors. BDNF Val/Met did not compensate for developing type 2 diabetes with high-energy intake. Additionally, indexes of insulin resistance and insulin secretion showed the same gene-energy interaction as type 2 diabetes. BDNF Val/Met and Met/Met variants (rs6265) decreases the risk for

  19. Transgenerational Glucose Intolerance of Tumor Necrosis Factor with Epigenetic Alteration in Rat Perirenal Adipose Tissue Induced by Intrauterine Hyperglycemia.

    Science.gov (United States)

    Su, Rina; Yan, Jie; Yang, Huixia

    2016-01-01

    Changes in DNA methylation may play a role in the genetic mechanism underlying glucose intolerance in the offspring of mothers with diabetes. Here, we established a rat model of moderate intrauterine hyperglycemia induced by streptozotocin to detect glucose and lipid metabolism of first-generation (F1) and second-generation (F2) offspring. Moderate intrauterine hyperglycemia induced high body weight in F1 and F2 offspring of diabetic mothers. F1 offspring had impaired glucose tolerance and abnormal insulin level. Additionally, F1 and F2 offspring that were exposed to intrauterine hyperglycemia had impaired insulin secretion from the islets. The tumor necrosis factor (Tnf) gene was upregulated in perirenal adipose tissue from F1 offspring and relatively increased in F2 offspring. Both F1 and F2 offspring showed similar hypomethylation level at the -1952 site of Tnf. We confirmed that DNA methylation occurs in offspring exposed to intrauterine hyperglycemia and that the DNA methylation is intergenerational and inherited.

  20. On the status and comparison of glucose intolerance in female breast cancer patients at initial diagnosis and during chemotherapy through an oral glucose tolerance test.

    Directory of Open Access Journals (Sweden)

    Lin-jie Lu

    Full Text Available AIMS: This study is to estimate the status and comparison of glucose intolerance in female breast cancer patients at initial diagnosis and during chemotherapy through an oral glucose tolerance test (OGTT, as well as to learn the effect of chemotherapy on the glucose metabolism of breast cancer patients. METHODS: All the 79 breast cancer patients at initial diagnosis, with the mean age of 53.2 years, and 96 breast cancer patients before the 5th or 6th cycle of chemotherapy, with the mean age of 51.5 years, participated in the study from December 2012 to October 2013. After an overnight fast, participants underwent OGTT test, and fasting and 2-hour glucose levels were measured to identify undiagnosed diabetes and prediabetes (i.e., impaired fasting glucose or impaired glucose tolerance in them. Previously diagnosed diabetes among the female breast cancer patients was determined on the self-report and the medical record. RESULTS: The overall incidences of total normal glucose tolerance, prediabetes, diabetes in female breast cancer patients at initial diagnosis and during chemotherapy were 24.1% and 38.5% (p0.05, respectively, and the differences of normal glucose tolerance and prediabetes instead of diabetes between the two groups were statistically significant. About 84% of the total diabetes and prediabetes in the female breast cancer patients at initial diagnosis and 79.7% of those during chemotherapy need to be diagnosed with OGTT. CONCLUSIONS: Breast cancer patients have high incidences of diabetes and prediabetes. After chemotherapy even with steroids, some breast cancer patients with abnormal glucose metabolism may even become normal. Isolated hyperglycemia 2 hours after glucose loading is common, and OGTT should be made for breast cancer patients at initial diagnosis and during chemotherapy.

  1. Tissue inhibitor of matrix metalloproteinase-1 is required for high-fat diet-induced glucose intolerance and hepatic steatosis in mice

    DEFF Research Database (Denmark)

    Fjære, Even; Andersen, Charlotte; Myrmel, Lene Secher

    2015-01-01

    -induced glucose intolerance and hepatic steatosis using the Timp1 null mice. METHODS: Timp1 knockout (TKO) and wild type (TWT) mice were fed chow, high-fat diet (HFD) or intermediate fat and sucrose diet (IFSD). We determined body weight, body composition, lipid content of the liver, energy intake, energy...... and had lower energy efficiency than TWT mice when fed HFD, but not when fed chow or IFSD. Importantly, TKO mice were protected from development of HFD- as well as IFSD-induced glucose intolerance, hepatic steatosis, and altered expression of genes involved in hepatic lipid metabolism and inflammation....... CONCLUSION: Collectively, our results indicate that TIMP-1 contributes to the development of diet-induced hepatic steatosis and glucose intolerance and may be a potential therapeutic target....

  2. The effect of altered gut flora on glucose intolerance in C57BL/6NTac mice

    DEFF Research Database (Denmark)

    Rune, Ida; Ellekilde, Merete; Hansen, Camilla Hartmann Friis

    Recent studies have shown that long term broad spectrum antibiotic treatment improves glucose tolerance in mice. We hypothesize that it is primarily in the early life that altering of the gut microbiota will have an impact on glucose intoleance.....

  3. The effect of altered gut flora on glucose intolerance in C57BL/6NTac mice

    DEFF Research Database (Denmark)

    Rune, Ida; Ellekilde, Merete; Hansen, Camilla Hartmann Friis

    Recent studies have shown that long term broad spectrum antibiotic treatment improves glucose tolerance in mice. We hypothesize that it is primarily in the early life that altering of the gut microbiota will have an impact on glucose intoleance........Recent studies have shown that long term broad spectrum antibiotic treatment improves glucose tolerance in mice. We hypothesize that it is primarily in the early life that altering of the gut microbiota will have an impact on glucose intoleance.....

  4. Host-microbiota interaction induces bi-phasic inflammation and glucose intolerance in mice

    DEFF Research Database (Denmark)

    Molinaro, Antonio; Caesar, Robert; Holm, Louise Mannerås

    2017-01-01

    OBJECTIVE: Gut microbiota modulates adiposity and glucose metabolism in humans and mice. Here we investigated how colonization of germ-free (GF) mice affects kinetics of adiposity and glucose metabolism. METHODS: Adiposity and glucose metabolism were evaluated at different time points in ex-GF an...

  5. Chronic erythropoietin treatment improves diet-induced glucose intolerance in rats

    DEFF Research Database (Denmark)

    Caillaud, Corinne; Mechta, Mie; Ainge, Heidi

    2015-01-01

    Erythropoietin (EPO) ameliorates glucose metabolism through mechanisms not fully understood. In this study, we investigated the effect of EPO on glucose metabolism and insulin signaling in skeletal muscle. A 2-week EPO treatment of rats fed with a high-fat diet (HFD) improved fasting glucose leve...

  6. Fructose Malabsorption and Intolerance: Effects of Fructose with and without Simultaneous Glucose Ingestion

    OpenAIRE

    Latulippe, Marie E.; Skoog, Suzanne M.

    2011-01-01

    Concern exists that increasing fructose consumption, particularly in the form of high-fructose corn syrup, is resulting in increasing rates of fructose intolerance and aggravation of clinical symptoms in individuals with irritable bowel syndrome. Most clinical trials designed to test this hypothesis have used pure fructose, a form not commonly found in the food supply, often in quantities and concentrations that exceed typical fructose intake levels. In addition, the amount of fructose provid...

  7. Association of genetic variants of melatonin receptor 1B with gestational plasma glucose level and risk of glucose intolerance in pregnant Chinese women.

    Directory of Open Access Journals (Sweden)

    Shunyao Liao

    Full Text Available BACKGROUND: This study aimed to explore the association of MTNR1B genetic variants with gestational plasma glucose homeostasis in pregnant Chinese women. METHODS: A total of 1,985 pregnant Han Chinese women were recruited and evaluated for gestational glucose tolerance status with a two-step approach. The four MTNR1B variants rs10830963, rs1387153, rs1447352, and rs2166706 which had been reported to associate with glucose levels in general non-pregnant populations, were genotyped in these women. Using an additive model adjusted for age and body mass index (BMI, association of these variants with gestational fasting and postprandial plasma glucose (FPG and PPG levels were analyzed by multiple linear regression; relative risk of developing gestational glucose intolerance was calculated by logistic regression. Hardy-Weinberg Equilibrium was tested by Chi-square and linkage disequilibrium (LD between these variants was estimated by measures of D' and r(2. RESULTS: In the pregnant Chinese women, the MTNR1B variant rs10830963, rs1387153, rs2166706 and rs1447352 were shown to be associated with the increased 1 hour PPG level (p=8.04 × 10(-10, 5.49 × 10(-6, 1.89 × 10(-5 and 0.02, respectively. The alleles were also shown to be associated with gestational glucose intolerance with odds ratios (OR of 1.64 (p=8.03 × 10(-11, 1.43 (p=1.94 × 10(-6, 1.38 (p=1.63 × 10(-5 and 1.24 (p=0.007, respectively. MTNR1B rs1387153, rs2166706 were shown to be associated with gestational FPG levels (p=0.04. Our data also suggested that, the LD pattern of these variants in the studied women conformed to that in the general populations: rs1387153 and rs2166706 were in high LD, they linked moderately with rs10830963, but might not linked with rs1447352;rs10830963 might not link with rs1447352, either. In addition, the MTNR1B variants were not found to be associated with any other traits tested. CONCLUSIONS: The MTNR1B is likely to be involved in the regulation of glucose

  8. Glucose intolerance and General Health Questionnaire 12-item version scores of male two-shift workers stratified by precariousness of work.

    Science.gov (United States)

    Kawada, Tomoyuki

    2016-01-01

    This study examined the relationship between precariousness of work, glucose intolerance and psychological wellbeing for male workers, stratified by age. I recruited 2542 manufacturing two-shift workers, aged from 35 to 54 years. Glucose intolerance was defined as fasting plasma glucose of ≥100mg/dL or current medication of diabetes mellitus. The rating scale of General Health Questionnaire 12-item version (GHQ-12) was used for evaluating psychological well-being. There was a significant increase in the prevalence of glucose intolerance by aging in permanent workers. In addition, the prevalence of glucose intolerance except 30s and the prevalence of positive GHQ-12 scores except 50s of permanent workers were both significantly higher than that of temporary workers in each age class. Temporary workers in this study sign contracts for 3 years, and heather worker's effect, compared with permanent workers, would be reflected in this study. Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  9. Acute, but not Chronic, Exposure to Arsenic Provokes Glucose Intolerance in Rats: Possible Roles for Oxidative Stress and the Adrenergic Pathway.

    Science.gov (United States)

    Rezaei, Mohsen; Khodayar, Mohammd Javad; Seydi, Enayatollah; Soheila, Alboghobeish; Parsi, Isa Kazemzadeh

    2017-06-01

    Health problems due to heavy metals have become a worldwide concern. Along with its carcinogenicity, arsenic exposure results in impairment of glucose metabolism and insulin secretion as well as altered gene expression and signal transduction. However, the exact mechanism behind the behaviour of arsenic on glucose homeostasis and insulin secretion has not yet been fully understood. Fasting blood sugar and glucose tolerance tests were evaluated. In this study, we demonstrated that arsenic, when acutely administered, induced glucose intolerance in rats, although its chronic oral exposure did not provoke any glucose intolerance or hyperglycemia in rats. The protective activity of N-acetylcysteine, carvedilol and propranolol in male rats exposed to arsenic were also assessed, and N-acetylcysteine, particularly at 40 and 80 mg/kg, prevented the glucose intolerance induced in rats by arsenic. The present study showed that acute, but not chronic, contact with arsenic generates significant changes in the normal glucose tolerance pattern that may be due fundamentally to overproduction of reactive oxygen species and oxidative stress and is preventable by using N-acetylcysteine, a thiol-containing antioxidant. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

  10. Optimal therapy for patients with hepatocellular carcinoma and resistance or intolerance to sorafenib: challenges and solutions

    Directory of Open Access Journals (Sweden)

    Ray EM

    2017-11-01

    Full Text Available Emily M Ray, Hanna K Sanoff Division of Hematology/Oncology, University of North Carolina, Chapel Hill, NC, USA Abstract: The only US Food and Drug Administration (FDA-approved first-line systemic therapy for hepatocellular carcinoma (HCC is sorafenib; however, resistance or intolerance to sorafenib is unfortunately common. In this review, we briefly describe systemic therapies that can be considered for patients with HCC who show resistance or intolerance to sorafenib. For all patients with HCC who need systemic therapy, we strongly advocate for participation in clinical trials. Cytotoxic chemotherapy plays a minor role in the treatment of advanced HCC, with some data supporting the use of FOLFOX (infusional fluorouracil, leucovorin, and oxaliplatin and GEMOX (gemcitabine-oxaliplatin. Multi-target kinase inhibitors such as lenvantinib and regorafenib have recently met their primary endpoints as first- and second-line therapy, respectively, with regorafenib now representing the only FDA-approved drug for second-line treatment of HCC. Other targeted therapies remain under investigation, but results so far have not significantly changed clinical practice. Immunotherapy is an interesting area of research in the treatment of HCC with preclinical and early clinical data demonstrating exciting results; thus numerous investigational studies are currently focusing on immunotherapy in the treatment of HCC. While systemic treatment options in HCC remain a challenge for providers, in this review, we summarize the current literature and highlight areas of progress with respect to the treatment of patients with HCC and resistance or intolerance to sorafenib. Keywords: liver cancer, chemotherapy, immunotherapy

  11. Exposure to Common Food Additive Carrageenan Alone Leads to Fasting Hyperglycemia and in Combination with High Fat Diet Exacerbates Glucose Intolerance and Hyperlipidemia without Effect on Weight

    Directory of Open Access Journals (Sweden)

    Sumit Bhattacharyya

    2015-01-01

    Full Text Available Aims. Major aims were to determine whether exposure to the commonly used food additive carrageenan could induce fasting hyperglycemia and could increase the effects of a high fat diet on glucose intolerance and dyslipidemia. Methods. C57BL/6J mice were exposed to either carrageenan, high fat diet, or the combination of high fat diet and carrageenan, or untreated, for one year. Effects on fasting blood glucose, glucose tolerance, lipid parameters, weight, glycogen stores, and inflammation were compared. Results. Exposure to carrageenan led to glucose intolerance by six days and produced elevated fasting blood glucose by 23 weeks. Effects of carrageenan on glucose tolerance were more severe than from high fat alone. Carrageenan in combination with high fat produced earlier onset of fasting hyperglycemia and higher glucose levels in glucose tolerance tests and exacerbated dyslipidemia. In contrast to high fat, carrageenan did not lead to weight gain. In hyperinsulinemic, euglycemic clamp studies, the carrageenan-exposed mice had higher early glucose levels and lower glucose infusion rate and longer interval to achieve the steady-state. Conclusions. Carrageenan in the Western diet may contribute to the development of diabetes and the effects of high fat consumption. Carrageenan may be useful as a nonobese model of diabetes in the mouse.

  12. Exposure to common food additive carrageenan alone leads to fasting hyperglycemia and in combination with high fat diet exacerbates glucose intolerance and hyperlipidemia without effect on weight.

    Science.gov (United States)

    Bhattacharyya, Sumit; Feferman, Leo; Unterman, Terry; Tobacman, Joanne K

    2015-01-01

    Major aims were to determine whether exposure to the commonly used food additive carrageenan could induce fasting hyperglycemia and could increase the effects of a high fat diet on glucose intolerance and dyslipidemia. C57BL/6J mice were exposed to either carrageenan, high fat diet, or the combination of high fat diet and carrageenan, or untreated, for one year. Effects on fasting blood glucose, glucose tolerance, lipid parameters, weight, glycogen stores, and inflammation were compared. Exposure to carrageenan led to glucose intolerance by six days and produced elevated fasting blood glucose by 23 weeks. Effects of carrageenan on glucose tolerance were more severe than from high fat alone. Carrageenan in combination with high fat produced earlier onset of fasting hyperglycemia and higher glucose levels in glucose tolerance tests and exacerbated dyslipidemia. In contrast to high fat, carrageenan did not lead to weight gain. In hyperinsulinemic, euglycemic clamp studies, the carrageenan-exposed mice had higher early glucose levels and lower glucose infusion rate and longer interval to achieve the steady-state. Carrageenan in the Western diet may contribute to the development of diabetes and the effects of high fat consumption. Carrageenan may be useful as a nonobese model of diabetes in the mouse.

  13. Repeated intraperitoneal injections of interleukin 1 beta induce glucose intolerance in normal rats

    DEFF Research Database (Denmark)

    Wogensen, L; Reimers, J; Mandrup-Poulsen, T

    1991-01-01

    Previous in vitro findings suggest the involvement of interleukin 1 (IL-1) in the pathogenesis of insulin-dependent diabetes mellitus. The aims of the present study were to investigate the effects of single or repeated ip injections of recombinant IL-1 beta on blood glucose and glucose tolerance ...

  14. Dietary fat proportionately enhances oxidative stress and glucose intolerance followed by impaired expression of the genes associated with mitochondrial biogenesis.

    Science.gov (United States)

    Das, Nabanita; Mandala, Ashok; Bhattacharjee, Sudarshan; Mukherjee, Debasri; Bandyopadhyay, Debasish; Roy, Sib Sankar

    2017-04-19

    Consumption of food that surpasses the metabolic necessity of the body leads to an epidemic condition termed obesity, which causes several metabolic disorders including oxidative damage. Dietary intervention can enlighten the mechanisms and therapeutics associated with these metabolic disorders. The reported studies related to diet include fat of different kinds and from different sources, however they lack dose response aspects. Our study highlighted the importance of dietary fat modification in modulating oxidative stress-induced glucose intolerance. Animals were maintained on a diet with a varied content of fat (30%/45%/60%) for 12 weeks and the 'withdrawal' group was fed a standard diet for another 10 weeks. The diet containing 60 energy% of fat displayed glucose intolerance, high ALT, low GSH levels and tissue-specific modulation of the prooxidant/antioxidant enzymatic activities in the liver/muscles. Prolonged sustenance of the 60 energy% fat containing diet-fed rats on standard diet led to the alteration of antioxidant activities, reversing the oxidative damage. Notably, the 'withdrawal' group displayed an organ-specific response towards dietary modification where the recovery of the antioxidant activities was observed to be much more pronounced in the liver as compared to the muscle. Further, we identified the differential expression of liver/muscle-specific genes associated with oxidative stress and mitochondrial biogenesis in response to the differing fat content. These genes can serve as markers for HFD-induced metabolic complications involving the liver/muscle. Altogether, our study has highlighted the novel area where obesity-induced oxidative stress linked alterations expressed diet and organ specific responses that are recovered by altering the dietary regimen. Future investigation of dietary modulation will open nascent avenues for developing therapeutic modalities addressing obesity-related metabolic complications.

  15. Glucagon-like peptide-1 receptor agonist treatment prevents glucocorticoid-induced glucose intolerance and islet-cell dysfunction in humans

    NARCIS (Netherlands)

    van Raalte, D.H.; van Genugten, R.E.; Linssen, M.M.L.; Ouwens, D.M.; Diamant, M.

    2011-01-01

    OBJECTIVE - Glucocorticoids (GCs) are regarded as diabetogenic because they impair insulin sensitivity and islet-cell function. This study assessed whether treatment with the glucagon-like peptide receptor agonist (GLP-1 RA) exenatide (EXE) could prevent GC-induced glucose intolerance. RESEARCH

  16. High Body Adiposity Drives Glucose Intolerance and Increases Cardiovascular Risk in Normoglycemic Subjects.

    Science.gov (United States)

    Pérez-Pevida, Belén; Díaz-Gutiérrez, Jesús; Miras, Alexander Dimitri; Silva, Camilo; Romero, Sonia; Salvador, Javier; Escalada, Javier; Frühbeck, Gema

    2018-03-09

    The objective of this study was to assess the utility of the 2-hour oral glucose tolerance test (OGTT) value to discriminate between different cardiometabolic profiles and examine the role of body composition in predicting the associated increased risk for glucose impairment, beta-cell dysfunction, and cardiovascular disease (CVD). Subjects with normal fasting glucose completed a 2-hour OGTT and were categorized to the carbohydrate metabolism alterations (CMAs) or the control group based on a 2-hour glucose threshold of 7.8 mmol/L. Body composition, visceral adipose tissue, OGTT-based parameters, and cardiovascular risk factors (CVRFs) such as hypertension, dyslipidemia, obstructive sleep apnea, nonalcoholic fatty liver disease, and smoking status were measured. Subjects with CMAs exhibited a significantly higher 1-hour postload glucose level and a greater decline in beta-cell function and CVRF profiles. After multivariate adjustment, an excess of total body and visceral fat was associated with an increased risk of CMAs, beta-cell dysfunction, CVRFs, and lower whole-body insulin sensitivity. These data support the etiopathogenic role of body and visceral fat in the development of glucose derangements and CVRFs early on in the metabolic dysregulation process. Thus, body composition analysis and OGTT assessment performed in individuals with normal fasting glucose enable a better identification of patients at risk of developing type 2 diabetes and CVD. © 2018 The Authors. Obesity published by Wiley Periodicals, Inc. on behalf of The Obesity Society (TOS).

  17. Glucose intolerance and the amount of visceral adipose tissue contribute to an increase in circulating triglyceride concentrations in Caucasian obese females.

    Science.gov (United States)

    Berings, Margot; Wehlou, Charline; Verrijken, An; Deschepper, Ellen; Mertens, Ilse; Kaufman, Jean-Marc; Van Gaal, Luc F; Ouwens, D Margriet; Ruige, Johannes B

    2012-01-01

    Lipotoxicity is a risk factor for developing obesity-related metabolic complications, including non-alcoholic fatty liver disease, type 2 diabetes (DM2), cardiovascular disease and stroke. Yet, the mechanisms underlying the development of lipotoxicity itself remain poorly understood. Here, we investigated whether glucose intolerance aggravates lipotoxicity by evaluating the association between triglyceride (TG) concentrations and glucose tolerance status in a cross-sectional study on obese Caucasian women at risk for DM2. 913 obese females unknown to have diabetes were recruited (mean age: 41.2 ± SD 12.3; median BMI: 36.2, IQR 32.9-40.2). Visceral (VAT) and subcutaneous abdominal adipose tissue volumes were quantified with computed tomography. Glucose, insulin, and triglyceride concentrations were determined in fasting state and following a 75 gram oral glucose tolerance test. Based on fasting and 2 h post-load glucose levels, 27% of the women had impaired glucose tolerance (IGT), and 8% had newly diagnosed DM2. Fasting TG concentrations were similar between the IGT- and DM2-groups, and increased as compared to women with normal glucose tolerance (NGT). Even when adjusting for age, hip circumference and VAT, fasting TG concentrations remained elevated as compared to NGT. Mixed modelling analysis of post-load responses showed that TG concentrations declined more slowly in the DM2-group as compared to IGT and NGT. However, when adjusting for VAT the difference in decline between the glucose tolerance groups disappeared. Glucose intolerance associates with elevated fasting TG concentrations in obese Caucasian women. We propose that glucose intolerance and increased VAT reduce lipid disposal mechanisms and may accelerate lipotoxicity.

  18. Glucose intolerance and the amount of visceral adipose tissue contribute to an increase in circulating triglyceride concentrations in Caucasian obese females.

    Directory of Open Access Journals (Sweden)

    Margot Berings

    Full Text Available CONTEXT: Lipotoxicity is a risk factor for developing obesity-related metabolic complications, including non-alcoholic fatty liver disease, type 2 diabetes (DM2, cardiovascular disease and stroke. Yet, the mechanisms underlying the development of lipotoxicity itself remain poorly understood. Here, we investigated whether glucose intolerance aggravates lipotoxicity by evaluating the association between triglyceride (TG concentrations and glucose tolerance status in a cross-sectional study on obese Caucasian women at risk for DM2. METHODS: 913 obese females unknown to have diabetes were recruited (mean age: 41.2 ± SD 12.3; median BMI: 36.2, IQR 32.9-40.2. Visceral (VAT and subcutaneous abdominal adipose tissue volumes were quantified with computed tomography. Glucose, insulin, and triglyceride concentrations were determined in fasting state and following a 75 gram oral glucose tolerance test. RESULTS: Based on fasting and 2 h post-load glucose levels, 27% of the women had impaired glucose tolerance (IGT, and 8% had newly diagnosed DM2. Fasting TG concentrations were similar between the IGT- and DM2-groups, and increased as compared to women with normal glucose tolerance (NGT. Even when adjusting for age, hip circumference and VAT, fasting TG concentrations remained elevated as compared to NGT. Mixed modelling analysis of post-load responses showed that TG concentrations declined more slowly in the DM2-group as compared to IGT and NGT. However, when adjusting for VAT the difference in decline between the glucose tolerance groups disappeared. CONCLUSIONS: Glucose intolerance associates with elevated fasting TG concentrations in obese Caucasian women. We propose that glucose intolerance and increased VAT reduce lipid disposal mechanisms and may accelerate lipotoxicity.

  19. The Development of Diet-Induced Obesity and Glucose Intolerance in C57Bl/6 Mice on a High-Fat Diet Consists of Distinct Phases

    Science.gov (United States)

    Williams, Lynda M.; Campbell, Fiona M.; Drew, Janice E.; Koch, Christiane; Hoggard, Nigel; Rees, William D.; Kamolrat, Torkamol; Thi Ngo, Ha; Steffensen, Inger-Lise; Gray, Stuart R.; Tups, Alexander

    2014-01-01

    High–fat (HF) diet-induced obesity and insulin insensitivity are associated with inflammation, particularly in white adipose tissue (WAT). However, insulin insensitivity is apparent within days of HF feeding when gains in adiposity and changes in markers of inflammation are relatively minor. To investigate further the effects of HF diet, C57Bl/6J mice were fed either a low (LF) or HF diet for 3 days to 16 weeks, or fed the HF-diet matched to the caloric intake of the LF diet (PF) for 3 days or 1 week, with the time course of glucose tolerance and inflammatory gene expression measured in liver, muscle and WAT. HF fed mice gained adiposity and liver lipid steadily over 16 weeks, but developed glucose intolerance, assessed by intraperitoneal glucose tolerance tests (IPGTT), in two phases. The first phase, after 3 days, resulted in a 50% increase in area under the curve (AUC) for HF and PF mice, which improved to 30% after 1 week and remained stable until 12 weeks. Between 12 and 16 weeks the difference in AUC increased to 60%, when gene markers of inflammation appeared in WAT and muscle but not in liver. Plasma proteomics were used to reveal an acute phase response at day 3. Data from PF mice reveals that glucose intolerance and the acute phase response are the result of the HF composition of the diet and increased caloric intake respectively. Thus, the initial increase in glucose intolerance due to a HF diet occurs concurrently with an acute phase response but these effects are caused by different properties of the diet. The second increase in glucose intolerance occurs between 12 - 16 weeks of HF diet and is correlated with WAT and muscle inflammation. Between these times glucose tolerance remains stable and markers of inflammation are undetectable. PMID:25170916

  20. Adverse pregnancy outcome in women with mild glucose intolerance: is there a clinically meaningful threshold value for glucose?

    DEFF Research Database (Denmark)

    Jensen, Dorte; Lauridsen, Lars Korsholm; Ovesen, Per Glud

    2008-01-01

    The diagnostic criteria of gestational diabetes mellitus (GDM) have been based on the risk of future maternal diabetes rather than the short-term risk of mother and infant. Our aim was to illustrate the relation between various adverse pregnancy outcomes and maternal glucose levels in women...

  1. Intrauterine protein restriction combined with early postnatal overfeeding was not associated with adult-onset obesity but produced glucose intolerance by pancreatic dysfunction.

    Science.gov (United States)

    Coutinho, Grazielle Vitória Ponti; Coutinho, Felipe Rodrigues; Faiad, Jaline Zandonato; Taki, Marina Satie; de Lima Reis, Silvia Regina; Ignácio-Souza, Letícia Martins; Paiva, Adriene Alexandra; Latorraca, Márcia Queiroz; Gomes-da-Silva, Maria Helena Gaíva; Martins, Maria Salete Ferreira

    2013-01-10

    We investigated if whether intrauterine protein restriction in combination with overfeeding during lactation would cause adult-onset obesity and metabolic disorders. After birth, litters from dams fed with control (17% protein) and low protein (6% protein) diets were adjusted to a size of four (CO and LO groups, respectively) or eight (CC and LC groups, respectively) pups. All of the offspring were fed a diet containing 12% protein from the time of weaning until they were 90 d old. Compared to the CC and LC groups, the CO and LO groups had higher relative and absolute food intakes, oxygen consumption and carbon dioxide production; lower brown adipose tissue weight and lipid content and greater weight gain and absolute and relative white adipose tissue weight and absolute lipid content. Compared with the CO and CC rats, the LC and LO rats exhibited higher relative food intake, brown adipose tissue weight and lipid content, reduced oxygen consumption, carbon dioxide production and spontaneous activity, increased relative retroperitoneal adipose tissue weight and unaltered absolute white adipose tissue weight and lipid content. The fasting serum glucose was similar among the groups. The area under the glucose curve was higher in the LO and CO rats than in the LC and CC rats. The basal insulinemia and homeostasis model assessment of insulin resistance (HOMA-IR) were lower in the LO group than in the other groups. The total area under the insulin curve for the LO rats was similar to the CC rats, and both were lower than the CO and LC rats. Kitt was higher in the LO, LC and CO groups than in the CC group. Thus, intrauterine protein restriction followed by overfeeding during lactation did not induce obesity, but produced glucose intolerance by impairing pancreatic function in adulthood.

  2. Folate treatment partially reverses gestational low-protein diet-induced glucose intolerance and the magnitude of reversal is age and sex dependent.

    Science.gov (United States)

    Blesson, Chellakkan S; Schutt, Amy; Mathew, Pretty R; Tanchico, Daren; Balakrishnan, Meena; Yallampalli, Uma; Yallampalli, Chandra

    2017-11-13

    Gestational low-protein (LP) programming causes glucose intolerance (GI) and insulin resistance (IR) in adult offspring. Folate supplementation has been shown to rescue the offspring from various programming effects. The aim of this study was to investigate whether folate supplementation during pregnancy reverses LP-induced GI and IR. Pregnant rats were fed control (20% protein), isocaloric low-protein (LP, 6%) or LP with 5 mg/kg folate (LPF) diets from gestational day 4 to delivery. The control diet was given during lactation and to pups after weaning. Glucose tolerance test was done at 1, 2, and 3 mo of age followed by euglycemic-hyperinsulinemic clamp at 4 mo. Rats were sacrificed at 4 mo and their gonadal, renal, inguinal, brown fat, and pancreas were weighed and expressed relative to their body weight. LP- and LPF-fed dams showed similar weight loss during late pregnancy after decreased feed intake. Both LP and LPF pups were smaller at birth but their weights caught up like that of controls by 3 mo. In males, folate supplementation reduced LP-induced GI at 2 mo (glucose area under the curve [AUC]: 1940 mmol/L × 180 min in LP, 1629 mmol/L × 180 min in LPF, and 1653 mmol/L × 180 min in controls; P reverses LP-induced GI and the magnitude of reversal is age and sex dependent. Furthermore, folate treatment does not reverse IR in either sex but makes it worse in males at 4 mo. The present study demonstrated that folate treatment is not sufficient to rescue the LP programming effects. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Hepatic branch vagus nerve plays a critical role in the recovery of post-ischemic glucose intolerance and mediates a neuroprotective effect by hypothalamic orexin-A.

    Directory of Open Access Journals (Sweden)

    Shinichi Harada

    Full Text Available Orexin-A (a neuropeptide in the hypothalamus plays an important role in many physiological functions, including the regulation of glucose metabolism. We have previously found that the development of post-ischemic glucose intolerance is one of the triggers of ischemic neuronal damage, which is suppressed by hypothalamic orexin-A. Other reports have shown that the communication system between brain and peripheral tissues through the autonomic nervous system (sympathetic, parasympathetic and vagus nerve is important for maintaining glucose and energy metabolism. The aim of this study was to determine the involvement of the hepatic vagus nerve on hypothalamic orexin-A-mediated suppression of post-ischemic glucose intolerance development and ischemic neuronal damage. Male ddY mice were subjected to middle cerebral artery occlusion (MCAO for 2 h. Intrahypothalamic orexin-A (5 pmol/mouse administration significantly suppressed the development of post-ischemic glucose intolerance and neuronal damage on day 1 and 3, respectively after MCAO. MCAO-induced decrease of hepatic insulin receptors and increase of hepatic gluconeogenic enzymes on day 1 after was reversed to control levels by orexin-A. This effect was reversed by intramedullary administration of the orexin-1 receptor antagonist, SB334867, or hepatic vagotomy. In the medulla oblongata, orexin-A induced the co-localization of cholin acetyltransferase (cholinergic neuronal marker used for the vagus nerve with orexin-1 receptor and c-Fos (activated neural cells marker. These results suggest that the hepatic branch vagus nerve projecting from the medulla oblongata plays an important role in the recovery of post-ischemic glucose intolerance and mediates a neuroprotective effect by hypothalamic orexin-A.

  4. Ozone Induces Glucose Intolerance and Systemic Metabolic Effects in Young and Aged Brown Norway Rats

    Science.gov (United States)

    Air pollutants have been associated with increased diabetes in humans. We hypothesized that ozone could impair glucose homeostasis by altering insulin signaling and/or endoplasmic reticular (ER) stress in very young and aged rats. Brown Norway (BN) rats, 1,4, 12, and 24 months ol...

  5. Glucose intolerance induced by blockade of central FGF receptors is linked to an acute stress response

    Directory of Open Access Journals (Sweden)

    Jennifer M. Rojas

    2015-08-01

    Conclusions: The effect of acute inhibition of central FGFR signaling to impair glucose tolerance likely involves a stress response associated with pronounced, but transient, sympathoadrenal activation and an associated reduction of insulin secretion. Whether this effect is a true consequence of FGFR blockade or involves an off-target effect of the FGFR inhibitor requires additional study.

  6. Host-microbiota interaction induces bi-phasic inflammation and glucose intolerance in mice

    DEFF Research Database (Denmark)

    Molinaro, Antonio; Caesar, Robert; Holm, Louise Mannerås

    2017-01-01

    expansion and inflammation. Importantly, re-colonization of antibiotic treated mice displays only the delayed phase of glucose impairment and adiposity, suggesting that the early phase may be unique to colonization of the immature GF mice gut. CONCLUSIONS: Our results provide new insights on host...

  7. Glucose intolerance and gestational diabetes risk in relation to sleep duration and snoring during pregnancy: a pilot study

    Directory of Open Access Journals (Sweden)

    Frederick Ihunnaya O

    2010-05-01

    Full Text Available Abstract Background Insufficient sleep and poor sleep quality, considered endemic in modern society, are associated with obesity, impaired glucose tolerance and diabetes. Little, however, is known about the consequences of insufficient sleep and poor sleep quality during pregnancy on glucose tolerance and gestational diabetes. Methods A cohort of 1,290 women was interviewed during early pregnancy. We collected information about sleep duration and snoring during early pregnancy. Results from screening and diagnostic testing for gestational diabetes mellitus (GDM were abstracted from medical records. Generalized linear models were fitted to derive relative risk (RR and 95% confidence intervals (95% CIs of GDM associated with sleep duration and snoring, respectively. Results After adjusting for maternal age and race/ethnicity, GDM risk was increased among women sleeping ≤ 4 hours compared with those sleeping 9 hours per night (RR = 5.56; 95% CI 1.31-23.69. The corresponding RR for lean women (2 was 3.23 (95% CI 0.34-30.41 and 9.83 (95% CI 1.12-86.32 for overweight women (≥ 25 kg/m2. Overall, snoring was associated with a 1.86-fold increased risk of GDM (RR = 1.86; 95% CI 0.88-3.94. The risk of GDM was particularly elevated among overweight women who snored. Compared with lean women who did not snore, those who were overweight and snored had a 6.9-fold increased risk of GDM (95% CI 2.87-16.6. Conclusions These preliminary findings suggest associations of short sleep duration and snoring with glucose intolerance and GDM. Though consistent with studies of men and non-pregnant women, larger studies that include objective measures of sleep duration, quality and apnea are needed to obtain more precise estimates of observed associations.

  8. Glucose intolerance and gestational diabetes risk in relation to sleep duration and snoring during pregnancy: a pilot study

    Science.gov (United States)

    2010-01-01

    Background Insufficient sleep and poor sleep quality, considered endemic in modern society, are associated with obesity, impaired glucose tolerance and diabetes. Little, however, is known about the consequences of insufficient sleep and poor sleep quality during pregnancy on glucose tolerance and gestational diabetes. Methods A cohort of 1,290 women was interviewed during early pregnancy. We collected information about sleep duration and snoring during early pregnancy. Results from screening and diagnostic testing for gestational diabetes mellitus (GDM) were abstracted from medical records. Generalized linear models were fitted to derive relative risk (RR) and 95% confidence intervals (95% CIs) of GDM associated with sleep duration and snoring, respectively. Results After adjusting for maternal age and race/ethnicity, GDM risk was increased among women sleeping ≤ 4 hours compared with those sleeping 9 hours per night (RR = 5.56; 95% CI 1.31-23.69). The corresponding RR for lean women (<25 kg/m2) was 3.23 (95% CI 0.34-30.41) and 9.83 (95% CI 1.12-86.32) for overweight women (≥ 25 kg/m2). Overall, snoring was associated with a 1.86-fold increased risk of GDM (RR = 1.86; 95% CI 0.88-3.94). The risk of GDM was particularly elevated among overweight women who snored. Compared with lean women who did not snore, those who were overweight and snored had a 6.9-fold increased risk of GDM (95% CI 2.87-16.6). Conclusions These preliminary findings suggest associations of short sleep duration and snoring with glucose intolerance and GDM. Though consistent with studies of men and non-pregnant women, larger studies that include objective measures of sleep duration, quality and apnea are needed to obtain more precise estimates of observed associations. PMID:20470416

  9. Regulation of glucose dynamics by noninvasive peripheral electrical stimulation in normal and insulin-resistant rats.

    Science.gov (United States)

    Catalogna, Merav; Fishman, Sigal; Halpern, Zamir; Ben-Shlomo, Shani; Nevo, Uri; Ben-Jacob, Eshel

    2016-06-01

    The epidemic nature of type 2 diabetes mellitus (T2DM), along with the downsides of current treatments, has raised the need for therapeutic alternatives. We studied normo-glycemic and high-fat diet (HFD), induced insulin-resistant Wistar Han rats for 2 to 3weeks. Rats received peripheral electrical stimulation (PES) treatment (2Hz/16Hz bursts, 10mA) in their hind limbs for 3min, 3 times per week. Glucose tolerance was evaluated by using a glucose tolerance test at the beginning and again at the end of the study. The effect of an acute PES treatment on metabolic rates of glucose appearance and turnover was measured by using the hyperinsulinemic-euglycemic clamp (HEGC) test. Repeated PES treatment significantly inhibited the progression of glucose intolerance in normal and insulin-resistant rats and prevented HFD-induced gains in body weight and fat mass. Acute treatment induced a prolonged effect on glucose turnover, as evaluated by the HEGC test. Increased hepatic glucose output was observed during the basal state (Pinsulin (41.1%, Pinsulin sensitivity in rats. Repeated PES treatment may have a beneficial effect on HFD-induced adiposity and control of body weight. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Inhibition of the gut enzyme intestinal alkaline phosphatase may explain how aspartame promotes glucose intolerance and obesity in mice

    Science.gov (United States)

    Gul, Sarah S.; Hamilton, A. Rebecca L.; Munoz, Alexander R.; Phupitakphol, Tanit; Liu, Wei; Hyoju, Sanjiv K.; Economopoulos, Konstantinos P.; Morrison, Sara; Hu, Dong; Zhang, Weifeng; Gharedaghi, Mohammad Hadi; Huo, Haizhong; Hamarneh, Sulaiman R.; Hodin, Richard A.

    2017-01-01

    Diet soda consumption has not been associated with tangible weight loss. Aspartame (ASP) commonly substitutes sugar and one of its breakdown products is phenylalanine (PHE), a known inhibitor of intestinal alkaline phosphatase (IAP), a gut enzyme shown to prevent metabolic syndrome in mice. We hypothesized that ASP consumption might contribute to the development of metabolic syndrome based on PHE’s inhibition of endogenous IAP. The design of the study was such that for the in vitro model, IAP was added to diet and regular soda, and IAP activity was measured. For the acute model, a closed bowel loop was created in mice. ASP or water was instilled into it and IAP activity was measured. For the chronic model, mice were fed chow or high-fat diet (HFD) with/without ASP in the drinking water for 18 weeks. The results were that for the in vitro study, IAP activity was lower (p water group (48.1 ± 1.6 vs 42.4 ± 3.1, p = 0.0001). Significant difference in glucose intolerance between the HFD ± ASP groups (53 913 ± 4000.58 (mg·min)/dL vs 42 003.75 ± 5331.61 (mg·min)/dL, respectively, p = 0.02). Fasting glucose and serum tumor necrosis factor-alpha levels were significantly higher in the HFD + ASP group (1.23- and 0.87-fold increases, respectively, p = 0.006 and p = 0.01). In conclusion, endogenous IAP’s protective effects in regard to the metabolic syndrome may be inhibited by PHE, a metabolite of ASP, perhaps explaining the lack of expected weight loss and metabolic improvements associated with diet drinks. PMID:27997218

  11. Chemical derivatives of docosahexaenoic acid prevent glucose intolerance in mice fed a high-fat diet

    Czech Academy of Sciences Publication Activity Database

    Rossmeisl, Martin; Jílková, Zuzana; Jeleník, Tomáš; Hensler, Michal; Flachs, Pavel; Mohamed-Ali, V.; Bryhn, M.; Kopecký, Jan

    2007-01-01

    Roč. 31, Suppl.1 (2007), S76-S76 ISSN 0307-0565. [European congress on obesity /15./. 22.04.2007-25.04.2007, Budapest] Institutional research plan: CEZ:AV0Z50110509 Keywords : obesity * insulin resistance * DHA * C57BL/6N mice Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition

  12. Potentiation of insulin secretion and improvement of glucose intolerance by combining a novel G protein-coupled receptor 40 agonist DS-1558 with glucagon-like peptide-1 receptor agonists.

    Science.gov (United States)

    Nakashima, Ryutaro; Yano, Tatsuya; Ogawa, Junko; Tanaka, Naomi; Toda, Narihiro; Yoshida, Masao; Takano, Rieko; Inoue, Masahiro; Honda, Takeshi; Kume, Shoen; Matsumoto, Koji

    2014-08-15

    G protein-coupled receptor 40 (GPR40) is a Gq-coupled receptor for free fatty acids predominantly expressed in pancreatic β-cells. In recent years, GPR40 agonists have been investigated for use as novel therapeutic agents in the treatment of type 2 diabetes. We discovered a novel small molecule GPR40 agonist, (3S)-3-ethoxy-3-(4-{[(1R)-4-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]oxy}phenyl)propanoic acid (DS-1558). The GPR40-mediated effects of DS-1558 on glucose-stimulated insulin secretion were evaluated in isolated islets from GPR40 knock-out and wild-type (littermate) mice. The GPR40-mediated effects on glucose tolerance and insulin secretion were also confirmed by an oral glucose tolerance test in these mice. Furthermore, oral administration of DS-1558 (0.03, 0.1 and 0.3mg/kg) significantly and dose-dependently improved hyperglycemia and increased insulin secretion during the oral glucose tolerance test in Zucker fatty rats, the model of insulin resistance and glucose intolerance. Next, we examined the combination effects of DS-1558 with glucagon like peptide-1 (GLP-1). DS-1558 not only increased the glucose-stimulated insulin secretion by GLP-1 but also potentiated the maximum insulinogenic effects of GLP-1 after an intravenous glucose injection in normal Sprague Dawley rats. Furthermore, the glucose lowering effects of exendin-4, a GLP-1 receptor agonist, were markedly potentiated by the DS-1558 (3mg/kg) add-on in diabetic db/db mice during an intraperitoneal glucose tolerance test. In conclusion, our results indicate that add-on GPR40 agonists to GLP-1 related agents might be a potential treatment compared to single administration of these compounds. Therefore the combinations of these agents are a novel therapeutic option for type 2 diabetes. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Disaccharide intolerance

    Directory of Open Access Journals (Sweden)

    Radlović Nedeljko

    2010-01-01

    Full Text Available Disaccharide intolerance presents a pathogenic heterogeneous and most complex clinical entity. It usually occurs due to primary or secondary deficit of disaccharide activity, and rarely because of disorders of absorption or monomer metabolism. Symptomatology of disaccharide maldigestion and/or malabsorption depends on the severity of the basic disorder, the level of its overload and the patient’s age. In the youngest children, due to a rapid gastrointestinal transit and a low compensatory capacity of the colon, osmotic-fermentative diarrhoea forms the basis of clinical features. Diarrhoeal disorder can be occasionally so intensive that it disturbs not only water and electrolytic balance, but also the nutritive status of the child. In older children and adults, as well as in milder forms of the disorder, the symptomatology, most often without diarrhoea, is dominated by abdominal colic, loud peristaltic sounds, meteorism and increased flatulence. Metabolic disorders followed by conversion disorders of galactose and fructose into glucose are characterized by a hypoglycaemic crisis, as well as by various multisystemic damages due to the deposit of toxic metabolic products. The diagnosis of gastrointestinal forms of disaccharide intolerance is based on the pathologic clinical and laboratory response during the overload test, while that of the metabolic form is based on the confirmed presence of specific enzyme and/or genetic defect. Treatment of disaccharide intolerance is based on the elimination diet. Besides, in the secondary forms of the disorder, it is also necessary to apply the treatment of the basic disease.

  14. Loss of Foxd3 Results in Decreased β-Cell Proliferation and Glucose Intolerance During Pregnancy

    Science.gov (United States)

    Plank, Jennifer L.; Frist, Audrey Y.; LeGrone, Alison W.; Magnuson, Mark A.

    2011-01-01

    A complete molecular understanding of β-cell mass expansion will be useful for the improvement of therapies to treat diabetic patients. During normal periods of metabolic challenges, such as pregnancy, β-cells proliferate, or self-renew, to meet the new physiological demands. The transcription factor Forkhead box D3 (Foxd3) is required for maintenance and self-renewal of several diverse progenitor cell lineages, and Foxd3 is expressed in the pancreatic primordium beginning at 10.5 d postcoitum, becoming localized predominantly to β-cells after birth. Here, we show that mice carrying a pancreas-specific deletion of Foxd3 have impaired glucose tolerance, decreased β-cell mass, decreased β-cell proliferation, and decreased β-cell size during pregnancy. In addition, several genes known to regulate proliferation, Foxm1, Skp2, Ezh2, Akt2, and Cdkn1a, are misregulated in islets isolated from these Foxd3 mutant mice. Together, these data place Foxd3 upstream of several pathways critical for β-cell mass expansion in vivo. PMID:21952247

  15. Abnormal glucose metabolism is associated with reduced left ventricular contractile reserve and exercise intolerance in patients with chronic heart failure

    DEFF Research Database (Denmark)

    Egstrup, M; Kistorp, C N; Schou, M

    2013-01-01

    intolerance related to diabetes. CONCLUSION: Diabetes, known or newly detected by OGTT, is independently associated with reduced LV contractile reserve and exercise...... intolerance in outpatients with systolic HF. These findings may offer one explanation for the excess mortality related to diabetes in HF....

  16. Glucose-induced insulin resistance of skeletal-muscle glucose transport and uptake

    DEFF Research Database (Denmark)

    Richter, Erik; Hansen, B F; Hansen, S A

    1988-01-01

    , impairment of insulin action on muscle glucose transport and uptake. Thus maximal insulin-stimulated glucose uptake at 12 mM-glucose decreased from 34.8 +/- 1.9 to 11.5 +/- 1.1 mumol/h per g (mean +/- S.E.M., n = 10) during 5 h perfusion. This decrease in glucose uptake was accompanied by a similar change...... in the presence of glucose and insulin. The data indicate that exposure to a moderately increased glucose concentration (12 mM) leads to rapidly developing resistance of skeletal-muscle glucose transport and uptake to maximal insulin stimulation. The effect of glucose is enhanced by simultaneous insulin exposure......, whereas exposure for 5 h to insulin itself does not cause measurable resistance to maximal insulin stimulation....

  17. Glucose intolerance in the West African Diaspora: a skeletal muscle fibre type distribution hypothesis.

    Science.gov (United States)

    Nielsen, J; Christensen, D L

    2011-08-01

    In the United States, Black Americans are largely descendants of West African slaves; they have a higher relative proportion of obesity and experience a higher prevalence of diabetes than White Americans. However, obesity rates alone cannot explain the higher prevalence of type 2 diabetes. Type 2 diabetes is characterized by insulin resistance and beta-cell dysfunction. We hypothesize that the higher prevalence of type 2 diabetes in African Americans (as compared to White Americans) is facilitated by an inherited higher percentage of skeletal muscle fibre type II and a lower percentage of skeletal muscle fibre type I. Skeletal muscle fibre type II is less oxidative and more glycolytic than skeletal muscle fibre type I. Lower oxidative capacity is associated with lower fat oxidation and a higher disposal of lipids, which are stored as muscular adipose tissue in higher amounts in Black compared to White Americans. In physically active individuals, the influence of muscle fibre composition will not be as detrimental as in physically inactive individuals. This discrepancy is caused by the plasticity in the skeletal muscle fibre characteristics towards a higher activity of oxidative enzymes as a consequence of physical activity. We suggest that a higher percentage of skeletal muscle fibre type II combined with physical inactivity has an impact on insulin sensitivity and high prevalence of type 2 diabetes in Blacks of West African ancestry. © 2011 The Authors. Acta Physiologica © 2011 Scandinavian Physiological Society.

  18. Inhibition of the gut enzyme intestinal alkaline phosphatase may explain how aspartame promotes glucose intolerance and obesity in mice.

    Science.gov (United States)

    Gul, Sarah S; Hamilton, A Rebecca L; Munoz, Alexander R; Phupitakphol, Tanit; Liu, Wei; Hyoju, Sanjiv K; Economopoulos, Konstantinos P; Morrison, Sara; Hu, Dong; Zhang, Weifeng; Gharedaghi, Mohammad Hadi; Huo, Haizhong; Hamarneh, Sulaiman R; Hodin, Richard A

    2017-01-01

    Diet soda consumption has not been associated with tangible weight loss. Aspartame (ASP) commonly substitutes sugar and one of its breakdown products is phenylalanine (PHE), a known inhibitor of intestinal alkaline phosphatase (IAP), a gut enzyme shown to prevent metabolic syndrome in mice. We hypothesized that ASP consumption might contribute to the development of metabolic syndrome based on PHE's inhibition of endogenous IAP. The design of the study was such that for the in vitro model, IAP was added to diet and regular soda, and IAP activity was measured. For the acute model, a closed bowel loop was created in mice. ASP or water was instilled into it and IAP activity was measured. For the chronic model, mice were fed chow or high-fat diet (HFD) with/without ASP in the drinking water for 18 weeks. The results were that for the in vitro study, IAP activity was lower (p < 0.05) in solutions containing ASP compared with controls. For the acute model, endogenous IAP activity was reduced by 50% in the ASP group compared with controls (0.2 ± 0.03 vs 0.4 ± 0.24) (p = 0.02). For the chronic model, mice in the HFD + ASP group gained more weight compared with the HFD + water group (48.1 ± 1.6 vs 42.4 ± 3.1, p = 0.0001). Significant difference in glucose intolerance between the HFD ± ASP groups (53 913 ± 4000.58 (mg·min)/dL vs 42 003.75 ± 5331.61 (mg·min)/dL, respectively, p = 0.02). Fasting glucose and serum tumor necrosis factor-alpha levels were significantly higher in the HFD + ASP group (1.23- and 0.87-fold increases, respectively, p = 0.006 and p = 0.01). In conclusion, endogenous IAP's protective effects in regard to the metabolic syndrome may be inhibited by PHE, a metabolite of ASP, perhaps explaining the lack of expected weight loss and metabolic improvements associated with diet drinks.

  19. Glucose tolerance and insulin resistance in Indian children: relationship to infant feeding pattern.

    Science.gov (United States)

    Veena, S R; Krishnaveni, G V; Wills, A K; Hill, J C; Karat, S C; Fall, C H D

    2011-10-01

    Our objective was to examine whether longer duration of breast-feeding and later introduction of complementary foods are associated with lower glucose concentrations and insulin resistance (IR-HOMA) in Indian children. Breast-feeding duration (six categories from l [95% CI -0.10, -0.004]; p = 0.03) and IR-HOMA (β = -0.05 [95% CI -0.10, -0.001]; p = 0.046) at 5 years, adjusted for the child's sex, age, current BMI, socioeconomic status, parent's education, rural/urban residence, birthweight and maternal gestational diabetes status. Longer duration of breastfeeding was associated with higher 120-min glucose concentration at 5 years (β = 0.08 mmol/l [95% CI 0.001, 0.15; p = 0.03]) but lower 120-min glucose concentration at 9.5 years (β = -0.09 [95% CI -0.16, -0.03]; p = 0.006). Age at starting complementary foods was unrelated to the children's glucose tolerance and IR-HOMA. Within this cohort, in which prolonged breast-feeding was the norm, there was evidence of a protective effect of longer duration of breast-feeding against glucose intolerance at 9.5 years. At 5 years longer duration of breast-feeding was associated with lower IR-HOMA.

  20. Intolerant tolerance.

    Science.gov (United States)

    Khushf, G

    1994-04-01

    The Hyde Amendment and Roman Catholic attempts to put restrictions on Title X funding have been criticized for being intolerant. However, such criticism fails to appreciate that there are two competing notions of tolerance, one focusing on the limits of state force and accepting pluralism as unavoidable, and the other focusing on the limits of knowledge and advancing pluralism as a good. These two types of tolerance, illustrated in the writings of John Locke and J.S. Mill, each involve an intolerance. In a pluralistic context where the free exercise of religion is respected, John Locke's account of tolerance is preferable. However, it (in a reconstructed form) leads to a minimal state. Positive entitlements to benefits like artificial contraception or nontherapeutic abortions can legitimately be resisted, because an intolerance has already been shown with respect to those that consider the benefit immoral, since their resources have been coopted by taxation to advance an end that is contrary to their own. There is a sliding scale from tolerance (viewed as forbearance) to the affirmation of communal integrity, and this scale maps on to the continuum from negative to positive rights.

  1. Glucose-induced insulin resistance of skeletal-muscle glucose transport and uptake

    DEFF Research Database (Denmark)

    Richter, Erik; Hansen, B F; Hansen, S A

    1988-01-01

    in the presence of glucose and insulin. The data indicate that exposure to a moderately increased glucose concentration (12 mM) leads to rapidly developing resistance of skeletal-muscle glucose transport and uptake to maximal insulin stimulation. The effect of glucose is enhanced by simultaneous insulin exposure......, whereas exposure for 5 h to insulin itself does not cause measurable resistance to maximal insulin stimulation.......The ability of glucose and insulin to modify insulin-stimulated glucose transport and uptake was investigated in perfused skeletal muscle. Here we report that perfusion of isolated rat hindlimbs for 5 h with 12 mM-glucose and 20,000 microunits of insulin/ml leads to marked, rapidly developing...

  2. Glucagon suppression during OGTT worsens while suppression during IVGTT sustains alongside development of glucose intolerance in patients with chronic pancreatitis

    DEFF Research Database (Denmark)

    Knop, F K; Vilsbøll, T; Larsen, Steen

    2010-01-01

    To examine plasma glucagon responses to oral and intravenous (iv) glucose in patients with chronic pancreatitis (CP) and either normal glucose tolerance (NGT), secondary impaired glucose tolerance (IGT) or secondary diabetes mellitus (DM)....

  3. Age, BMI, and race are less important than random plasma glucose in identifying risk of glucose intolerance: the Screening for Impaired Glucose Tolerance Study (SIGT 5).

    Science.gov (United States)

    Ziemer, David C; Kolm, Paul; Weintraub, William S; Vaccarino, Viola; Rhee, Mary K; Caudle, Jane M; Irving, Jade M; Koch, David D; Narayan, K M Venkat; Phillips, Lawrence S

    2008-05-01

    Age, BMI, and race/ethnicity are used in National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and American Diabetes Association (ADA) guidelines to prompt screening for pre-diabetes and diabetes, but cutoffs have not been evaluated rigorously. Random plasma glucose (RPG) was measured and 75-g oral glucose tolerance tests were performed in 1,139 individuals without known diabetes. Screening performance was assessed by logistic regression and area under the receiver operating characteristic curve (AROC). NIDDK/ADA indicators age >45 years and BMI >25 kg/m(2) provided significant detection of both diabetes and dysglycemia (both AROCs 0.63), but screening was better with continuous-variable models of age, BMI, and race and better still with models of age, BMI, race, sex, and family history (AROC 0.78 and 0.72). However, screening was even better with RPG alone (AROCs 0.81 and 0.72). RPG >125 mg/dl could be used to prompt further evaluation with an OGTT. Use of age, BMI, and race/ethnicity in guidelines for screening to detect diabetes and pre-diabetes may be less important than evaluation of RPG. RPG should be investigated further as a convenient, inexpensive screen with good predictive utility.

  4. Gender-Specific Mechanisms Underlying the Amelioration of High-Fat Diet-Induced Glucose Intolerance in B-Cell-Activating Factor Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Bobae Kim

    Full Text Available It has recently been found that B cell activating factor (BAFF plays an important role in the regulation of energy homeostasis. We also have previously reported that BAFF deficiency reverses high-fat (HF diet-induced glucose intolerance by potentiating adipose tissue function. In the present study, we found that BAFF deficient (BAFF-/- mice exhibit gender-specific differences in protection against diet-induced glucose intolerance, and aimed to characterize the gender-dependent molecular alterations in energy metabolism. Under HF feeding conditions, serum BAFF level of female wild-type (WT mice was considerably higher than that of male mice. Despite increased body weight gain, both male and female BAFF-/- mice showed significantly improved glucose tolerance compared to their WT counterparts. Expressions of genes involved in glucose transport, thermogenesis and lipid oxidation were up-regulated in brown adipose tissues of both male and female BAFF-/- mice. Interestingly, the expression of thermogenic genes in subcutaneous adipose tissue was significantly enhanced in female BAFF-/- compared to WT mice, but the difference was not observed between male BAFF-/- and WT mice. The enhanced thermogenic program was confirmed by higher protein levels of UCP1 and irisin in female BAFF-/- than in WT mice. Additionally, adiponectin production in white adipose tissues and AMPK phosphorylation in subcutaneous adipose tissue were also significantly elevated in female BAFF-/- compared to WT mice, but not in male BAFF-/- mice. Our findings define a comprehensive scenario for the enhancing effect of BAFF depletion on glucose tolerance wherein the underlying mechanism is, at least in part, gender-specific, and suggest that gender difference should be considered as an important factor in the use of BAFF blockade as a therapeutic approach for the prevention and treatment of type 2 diabetes.

  5. Implication of a novel Gla-containing protein, Gas6 in the pathogenesis of insulin resistance, impaired glucose homeostasis, and inflammation: A review.

    Science.gov (United States)

    Dihingia, Anjum; Kalita, Jatin; Manna, Prasenjit

    2017-06-01

    Growth arrest specific 6 (Gas6), a vitamin K-dependent protein plays a significant role in the regulation of cellular homeostasis via binding with TAM-receptor tyrosine kinases. Several studies reported the role of Gas6 in cancer, glomerular injury, obesity, and inflammation, however, very little is known about its role in insulin resistance (IR) and impaired glucose metabolism. Majority of the studies reported an inverse correlation of Gas6 protein levels or gene polymorphism with plasma glucose, HbA1c, IR, and inflammatory cytokines among type 2 diabetes (T2D) and obese subjects. However, few studies reported a positive correlation of Gas6 protein levels or gene polymorphism with IR and inflammation among obese subjects. This review for the first time provides an overview of the association of Gas6 protein levels or gene polymorphism with IR, glucose intolerance, and inflammation among T2D and obese subjects. This review also depicts the probable mechanism underlying the association of Gas6 with glucose intolerance and inflammation. The outcome of this review will increase the understanding about the role of Gas6 in the pathogenesis of IR, glucose intolerance and inflammation and that should in turn lead to the design of clinical interventions to improve glucose metabolism and the lives of the T2D patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. High Intensity Resistive and Rowing Exercise Countermeasures Do Not Prevent Orthostatic Intolerance Following 70 Days of Bed Rest

    Science.gov (United States)

    Lee, Stuart M. C.; Stenger, Michael B.; Laurie, Steven S.; Ploutz-Snyder, Lori L.; Platts, Steven H.

    2015-01-01

    More than 60% of US astronauts participating in Mir and early International Space Station missions (greater than 5 months) were unable to complete a 10-min 80 deg head-up tilt test on landing day. This high incidence of post-spaceflight orthostatic intolerance may be related to limitations of the inflight exercise hardware that prevented high intensity training. PURPOSE: This study sought to determine if a countermeasure program that included intense lower-body resistive and rowing exercises designed to prevent cardiovascular and musculoskeletal deconditioning during 70 days of 6 deg head-down tilt bed rest (BR), a spaceflight analog, also would protect against post- BR orthostatic intolerance. METHODS: Sixteen males participated in this study and performed no exercise (Control, n=10) or performed an intense supine exercise protocol with resistive and aerobic components (Exercise, n=6). On 3 days/week, exercise subjects performed lower body resistive exercise and a 30-min continuous bout of rowing (greater than or equal to 75% max heart rate). On 3 other days/week, subjects performed only high-intensity, interval-style rowing. Orthostatic intolerance was assessed using a 15-min 80 deg head-up tilt test performed 2 days (BR-2) before and on the last day of BR (BR70). Plasma volume was measured using a carbon monoxide rebreathing technique on BR-3 and before rising on the first recovery day (BR+0). RESULTS: Following 70 days of BR, tilt tolerance time decreased significantly in both the Control (BR-2: 15.0 +/- 0.0, BR70: 9.9 +/- 4.6 min, mean +/- SD) and Exercise (BR-2: 12.2 +/- 4.7, BR70: 4.9 +/- 1.9 min) subjects, but the decreased tilt tolerance time was not different between groups (Control: -34 +/- 31, Exercise: -56 +/- 16%). Plasma volume also decreased (Control: -0.56 +/- 0.40, Exercise: -0.48 +/- 0.33 L) from pre to post-BR, with no differences between groups (Control: -18 +/- 11%, Exerciser: -15 +/-1 0%). CONCLUSIONS: These findings confirm previous reports

  7. Boehmeria nivea Stimulates Glucose Uptake by Activating Peroxisome Proliferator-Activated Receptor Gamma in C2C12 Cells and Improves Glucose Intolerance in Mice Fed a High-Fat Diet

    Directory of Open Access Journals (Sweden)

    Sung Hee Kim

    2013-01-01

    Full Text Available We examined the antidiabetic property of Boehmeria nivea (L. Gaud. Ethanolic extract of Boehmeria nivea (L. Gaud. (EBN increased the uptake of 2-[N-(nitrobenz-2-oxa-1,3-diazol-4-ylamino]-2-deoxy-d-glucose in C2C12 myotubes. To examine the mechanisms underlying EBN-mediated increase in glucose uptake, we examined the transcriptional activity and expression of peroxisome proliferator-activated receptor gamma (PPAR-γ, a pivotal target for glucose metabolism in C2C12 myotubes. We found that the EBN increased both the transcriptional activity and mRNA expression levels of PPAR-γ. In addition, we measured phosphorylation and expression levels of other targets of glucose metabolism, such as AMP-activated protein kinase (AMPK and protein kinase B (Akt/PKB. We found that EBN did not alter the phosphorylation or expression levels of these proteins in a time- or dose-dependent manner, which suggested that EBN stimulates glucose uptake through a PPAR-γ-dependent mechanism. Further, we investigated the antidiabetic property of EBN using mice fed a high-fat diet (HFD. Administration of 0.5% EBN reduced the HFD-induced increase in body weight, total cholesterol level, and fatty liver and improved the impaired fasting glucose level, blood insulin content, and glucose intolerance. These results suggest that EBN had an antidiabetic effect in cell culture and animal systems and may be useful for preventing diabetes.

  8. Insulin resistance in human subjects having impaired glucose regulation

    International Nuclear Information System (INIS)

    Khan, S.H.; Khan, F.A.; Ijaz, A.

    2007-01-01

    To determine insulin resistance in human subjects having impaired glucose regulation (IGR) by Homeostasis Model Assessment for Insulin Resistance (HOMA-IR). A total of 100 subjects with impaired glucose regulation were selected for evaluation of metabolic syndrome as per the criteria of National Cholesterol Education Program, Adult Treatment Panel III (NCEP, ATP III), along with 47 healthy age and gender-matched controls. Physical examination to determine blood pressure and waist circumference was carried out and so was sampling for plasma glucose, serum triglycerides, HDL-cholesterol and insulin. Insulin resistance was calculated by the HOMA-IR. Finally, subjects with and without metabolic syndrome were compared with controls (n=47), using one-way ANOVA for studying insulin resistance between groups, with Tukey's post-hoc comparison. The frequency of finding metabolic syndrome in cases of IGR remained 47%. The insulin resistance demonstrated stepwise worsening from control population (mean=1.54, 95 % CI: 1.77 - 2.37) to subjects suffering from only IGR (mean=2.07, 95 % CI: 1.77- 2.37) to metabolic syndrome (mean=2.67, 95 %, CI: 2.34 - 3.00) (p < 0.001). Patients with impaired glucose regulation may have significant insulin resistance. It is, thus, recommended that a vigorous search be made to measure insulin resistance in all cases diagnosed to have impaired glucose regulation. (author)

  9. Mice Abundant in Muricholic Bile Acids Show Resistance to Dietary Induced Steatosis, Weight Gain, and to Impaired Glucose Metabolism.

    Directory of Open Access Journals (Sweden)

    Ylva Bonde

    Full Text Available High endogenous production of, or treatment with muricholic bile acids, strongly reduces the absorption of cholesterol. Mice abundant in muricholic bile acids may therefore display an increased resistance against dietary induced weight gain, steatosis, and glucose intolerance due to an anticipated general reduction in lipid absorption. To test this hypothesis, mice deficient in steroid 12-alpha hydroxylase (Cyp8b1-/- and therefore abundant in muricholic acids were monitored for 11 weeks while fed a high fat diet. Food intake and body and liver weights were determined, and lipids in liver, serum and feces were measured. Further, responses during oral glucose and intraperitoneal insulin tolerance tests were evaluated. On the high fat diet, Cyp8b1-/- mice displayed less weight gain compared to wildtype littermates (Cyp8b1+/+. In addition, liver enlargement with steatosis and increases in serum LDL-cholesterol were strongly attenuated in Cyp8b1-/- mice on high fat diet. Fecal excretion of cholesterol was increased and there was a strong trend for doubled fecal excretion of free fatty acids, while excretion of triglycerides was unaltered, indicating dampened lipid absorption. On high fat diet, Cyp8b1-/- mice also presented lower serum glucose levels in response to oral glucose gavage or to intraperitoneal insulin injection compared to Cyp8b1+/+. In conclusion, following exposure to a high fat diet, Cyp8b1-/- mice are more resistant against weight gain, steatosis, and to glucose intolerance than Cyp8b1+/+ mice. Reduced lipid absorption may in part explain these findings. Overall, the results suggest that muricholic bile acids may be beneficial against the metabolic syndrome.

  10. Common variants in the ATP-sensitive K channel genes KCNJ11 (Kir6.2) and ABCC8 (SUR1) in relation to glucose intolerance: population-based studies and meta-analyses

    NARCIS (Netherlands)

    Dam, van R.M.; Hoebee, B.; Seidell, J.C.; Schaap, M.M.; Bruin, de T.W.; Feskens, E.J.M.

    2005-01-01

    Abstract Aims To evaluate the relation between common variants in the ATP-sensitive K(+) channel genes and glucose intolerance. Methods We conducted a meta-analysis of reported association studies in Caucasian populations for common variants in the ABCC8 (exons 16 and 18) and the KCNJ11 (E23K) gene

  11. Amelioration of high fat diet-induced glucose intolerance by blockade of Smad4 in pancreatic beta-cells.

    Science.gov (United States)

    Li, H Y; Oh, Y S; Lee, Y-J; Lee, E-K; Jung, H S; Jun, H-S

    2015-04-01

    In this study, we investigated whether Smad4 signaling is involved in the regulation of beta-cell function using a high fat diet (HFD)-induced obesity mouse model. Beta-cell-specific Smad4-knockout mice (Smad4(-/-)RIP-Cre(+); β-Smad4KO) were generated by mating Smad4 (flox/flox) mice with rat insulin promoter (RIP)-Cre mice. Mice were fed a HFD beginning at 6 weeks of age for 16 weeks. Body weight, food intake, fasting and fed glucose levels, and glucose and insulin tolerance were measured. The expression of Smad4 mRNA was significantly decreased in the islets of β-Smad4KO mice. In wild-type mice, Smad4 mRNA was significantly decreased at 18 weeks of age as compared with 8 weeks of age. On a regular chow diet, β-Smad4KO mice showed no differences in body weight, fed and fasting blood glucose levels, and glucose tolerance compared with wild-type mice. When fed a HFD, body weight gain was significantly reduced in β-Smad4KO mice as compared with wild-type mice, although the amount of food intake was not different. During the HFD, fed and fasting blood glucose levels, glucose stimulated insulin secretion, disposition index and glucose tolerance were significantly improved in β-Smad4KO mice as compared with wild-type mice. However, insulin tolerance tests showed no differences between the 2 groups. Inhibition of Smad4 in beta-cells conferred mild but significant improvements in glucose levels and glucose tolerance in HFD-induced obese mice. Therefore, regulation of Smad4 expression may be one of the mechanisms regulating physiological expansion of beta-cells during development of type 2 diabetes. © Georg Thieme Verlag KG Stuttgart · New York.

  12. [Food intolerance].

    Science.gov (United States)

    Zugasti Murillo, Ana

    2009-05-01

    Adverse food reactions are common in the general population. Nevertheless, our knowledge of the structure of food allergens and of the mechanisms involved is poor. In 1995 the European Academy of Allergology and Clinical Immunology suggested a classification based on the causative pathogenic mechanism. According to this classification, non-toxic reactions can be divided into food allergies when they recognize immunological mechanisms and food intolerance when there are no immunological implications. The treatment of food intolerance is avoidance of the particular food. There are specific treatments for some food intolerance (beta-galactosidases for the management of lactose intolerance).

  13. Enhanced glucagon-like peptide-1 (GLP-1) response to oral glucose in glucose-intolerant HIV-infected patients on antiretroviral therapy

    DEFF Research Database (Denmark)

    Andersen, Ove; Haugaard, Steen B; Holst, J J

    2005-01-01

    with NGT patients (1455+/-422 vs. 409+/-254 pmol/L/180 min, respectively; Pgroups (7689+/-1097 vs. 8041+/-998 pmol/L/180 min, respectively; not significant). In pooled study groups, the GIP incrAUC correlated positively with the ISR incr......OBJECTIVES: We investigated whether the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which are major regulators of glucose tolerance through the stimulation of insulin secretion, contribute to impaired glucose tolerance (IGT) among HIV......-infected patients on highly active antiretroviral therapy (HAART). METHODS: Eighteen HIV-infected male patients (six lipodystrophic and 12 nonlipodystrophic) with normal glucose tolerance (NGT) were compared with 10 HIV-infected male patients (eight lipodystrophic and two nonlipodystrophic) with IGT. Plasma...

  14. Diet supplementation with green tea extract epigallocatechin gallate prevents progression to glucose intolerance in db/db mice

    Directory of Open Access Journals (Sweden)

    Ortsäter Henrik

    2012-02-01

    Full Text Available Abstract Background Green tea was suggested as a therapeutic agent for the treatment of diabetes more than 70 years ago, but the mechanisms behind its antidiabetic effect remains elusive. In this work, we address this issue by feeding a green tea extract (TEAVIGO™ with a high content of epigallocatechin gallate (EGCG or the thiazolidinedione PPAR-γ agonist rosiglitazone, as positive control, to db/db mice, an animal model for diabetes. Methods Young (7 week-old db/db mice were randomized and assigned to receive diets supplemented with or without EGCG or rosiglitazone for 10 weeks. Fasting blood glucose, body weight and food intake was measured along the treatment. Glucose and insulin levels were determined during an oral glucose tolerance test after 10 weeks of treatment. Pancreata were sampled at the end of the study for blinded histomorphometric analysis. Islets were isolated and their mRNA expression analyzed by quantitative RT-PCR. Results The results show that, in db/db mice, EGCG improves glucose tolerance and increases glucose-stimulated insulin secretion. EGCG supplementation reduces the number of pathologically changed islets of Langerhans, increases the number and the size of islets, and heightens pancreatic endocrine area. These effects occurred in parallel with a reduction in islet endoplasmic reticulum stress markers, possibly linked to the antioxidative capacity of EGCG. Conclusions This study shows that the green tea extract EGCG markedly preserves islet structure and enhances glucose tolerance in genetically diabetic mice. Dietary supplementation with EGCG could potentially contribute to nutritional strategies for the prevention and treatment of type 2 diabetes.

  15. Bosutinib efficacy and safety in chronic phase chronic myeloid leukemia after imatinib resistance or intolerance : Minimum 24-month follow-up

    NARCIS (Netherlands)

    Gambacorti-Passerini, Carlo; Brümmendorf, Tim H; Kim, Dong-Wook; Turkina, Anna G; Masszi, Tamas; Assouline, Sarit; Durrant, Simon; Kantarjian, Hagop M; Khoury, H Jean; Zaritskey, Andrey; Shen, Zhi-Xiang; Jin, Jie; Vellenga, Edo; Pasquini, Ricardo; Mathews, Vikram; Cervantes, Francisco; Besson, Nadine; Turnbull, Kathleen; Leip, Eric; Kelly, Virginia; Cortes, Jorge E

    Bosutinib is an orally active, dual Src/Abl tyrosine kinase inhibitor for treatment of chronic myeloid leukemia (CML) following resistance/intolerance to prior therapy. Here, we report the data from the 2-year follow-up of a phase 1/2 open-label study evaluating the efficacy and safety of bosutinib

  16. Benefits of L-alanine or L-arginine supplementation against adiposity and glucose intolerance in monosodium glutamate-induced obesity.

    Science.gov (United States)

    Araujo, Thiago R; Freitas, Israelle N; Vettorazzi, Jean F; Batista, Thiago M; Santos-Silva, Junia C; Bonfleur, Maria L; Balbo, Sandra L; Boschero, Antonio C; Carneiro, Everardo M; Ribeiro, Rosane A

    2017-09-01

    L-alanine (Ala) and L-arginine (Arg) have been reported to regulate pancreatic β-cell physiology and to prevent body fat accumulation in diet-induced obesity. Here, we assessed growth and adiposity parameters, glucose tolerance, insulin secretion and the expression of insulin and nutrient-regulated proteins in monosodium glutamate (MSG)-obese mice supplemented with either Ala or Arg. Male newborn C57Bl/6 mice received a daily subcutaneous injection of MSG or saline solution (CTL group), during the first 6 days of life. From 30 to 90 days of age, MSG and CTL mice received or not 2.55 % Ala (CAla or MArg groups) or 1.51 % Arg-HCl (CArg or MArg groups) in their drinking water. Adult MSG mice displayed higher adiposity associated with lower phosphorylation of the adipogenic enzyme, ACC, in adipose tissue. Glucose intolerance in MSG mice was linked to lower insulin secretion and to lower expression of IRβ in adipose tissue, as well as AS160 phosphorylation in skeletal muscle. Perigonadal fat depots were smaller in Ala and Arg mice, while retroperitoneal fat pads were decreased by Ala supplementation only. Both Ala and Arg improved fed-state glycemia as well as IRβ and pAS160 content, but only Ala led to improved glucose tolerance and insulin secretion. Adipostatic signals were increased in MAla mice, as indicated by enhanced AMPK phosphorylation and pACC content in fat depots. Ala supplementation led to more pronounced metabolic improvements compared to Arg, possibly due to suppression of lipogenesis through activation of the AMPK/ACC pathway.

  17. A dietary pattern including nopal, chia seed, soy protein, and oat reduces serum triglycerides and glucose intolerance in patients with metabolic syndrome.

    Science.gov (United States)

    Guevara-Cruz, Martha; Tovar, Armando R; Aguilar-Salinas, Carlos A; Medina-Vera, Isabel; Gil-Zenteno, Lidia; Hernández-Viveros, Isaac; López-Romero, Patricia; Ordaz-Nava, Guillermo; Canizales-Quinteros, Samuel; Guillen Pineda, Luz E; Torres, Nimbe

    2012-01-01

    Metabolic syndrome (MetS) is a health problem throughout the world and is associated with cardiovascular disease and diabetes. Thus, the purpose of the present work was to evaluate the effects of a dietary pattern (DP; soy protein, nopal, chia seed, and oat) on the biochemical variables of MetS, the AUC for glucose and insulin, glucose intolerance (GI), the relationship of the presence of certain polymorphisms related to MetS, and the response to the DP. In this randomized trial, the participants consumed their habitual diet but reduced by 500 kcal for 2 wk. They were then assigned to the placebo (P; n = 35) or DP (n = 32) group and consumed the reduced energy diet plus the P or DP beverage (235 kcal) minus the energy provided by these for 2 mo. All participants had decreases in body weight (BW), BMI, and waist circumference during the 2-mo treatment (P < 0.0001); however, only the DP group had decreases in serum TG, C-reactive protein (CRP), and AUC for insulin and GI after a glucose tolerance test. Interestingly, participants in the DP group with MetS and the ABCA1 R230C variant had a greater decrease in BW and an increase in serum adiponectin concentration after 2 mo of dietary treatment than those with the ABCA1 R230R variant. The results from this study suggest that lifestyle interventions involving specific DP for the treatment of MetS could be more effective if local foods and genetic variations of the population are considered.

  18. [Fructose and fructose intolerance].

    Science.gov (United States)

    Buzás, György Miklós

    2016-10-01

    Although fructose was discovered in 1794, it was realised in recent decades only that its malabsorption can lead to intestinal symptoms while its excessive consumption induces metabolic disturbances. Fructose is a monosaccharide found naturally in most fruits and vegetables. Dietary intake of fructose has gradually increased in the past decades, especially because of the consumption of high fructose corn syrup. With its 16.4 kg/year consumption, Hungary ranks secondly after the United States. Fructose is absorbed in the small intestine by facilitated transport mediated by glucose transporter proteins-2 and -5, and arrives in the liver cells. Here it is transformed enzymatically into fructose-1-phosphate and then, fructose-1,5-diphosphate, which splits further into glyceraldehyde and dihydroxyacetone-phosphate, entering the process of glycolysis, triglyceride and uric acid production. The prevalence of fructose intolerance varies strongly, depending on the method used. The leading symptoms of fructose intolerance are similar, but less severe than those of lactose intolerance. Multiple secondary symptoms can also occur. A symptom-based diagnosis of fructose intolerance is possible, but the gold standard is the H 2 breath test, though this is less accurate than in lactose testing. Measuring fructosaemia is costly, cumbersome and not widely used. Fructose intolerance increases intestinal motility and sensitivity, promotes biofilm formation and contributes to the development of gastrooesophageal reflux. Long-term use of fructose fosters the development of dental caries and non-alcoholic steatohepatitis. Its role in carcinogenesis is presently investigated. The cornerstone of dietary management for fructose intolerance is the individual reduction of fructose intake and the FODMAP diet, led by a trained dietetician. The newly introduced xylose-isomerase is efficient in reducing the symptoms of fructose intolerance. Orv. Hetil., 2016, 157(43), 1708-1716.

  19. Enhanced glucagon-like peptide-1 (GLP-1) response to oral glucose in glucose-intolerant HIV-infected patients on antiretroviral therapy

    DEFF Research Database (Denmark)

    Andersen, O; Haugaard, S B; Holst, Jens Juul

    2005-01-01

    concentrations of GLP-1 and GIP were determined frequently during a 3-h, 75-g glucose tolerance test. Insulin secretion rates (ISRs) were calculated by deconvolution of C-peptide concentrations. RESULTS: The incremental area under the curve (incrAUC) for GLP-1 was increased by 250% in IGT patients compared...... with NGT patients (1455+/-422 vs. 409+/-254 pmol/L/180 min, respectively; PISR incr......, which may represent a compensatory mechanism rather than explain the IGT; (2) that the GIP response may be associated with ISR independently of plasma glucose in nondiabetic HIV-infected males on HAART....

  20. Lactose Intolerance

    Science.gov (United States)

    ... Abdominal pain Lactose intolerance Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  1. Lactose Intolerance

    Science.gov (United States)

    Lactose intolerance means that you cannot digest foods with lactose in them. Lactose is the sugar found in milk and foods made with milk. After eating foods with lactose in them, you may feel sick to your ...

  2. Cold intolerance

    Science.gov (United States)

    ... Causes Some causes of cold intolerance are: Anemia Anorexia nervosa Blood vessel problems, such as Raynaud phenomenon ... of being cold? Medical history: What is your diet like? How is your general health? What are ...

  3. Intestine-specific deletion of acyl-CoA:monoacylglycerol acyltransferase (MGAT) 2 protects mice from diet-induced obesity and glucose intolerance.

    Science.gov (United States)

    Nelson, David W; Gao, Yu; Yen, Mei-I; Yen, Chi-Liang Eric

    2014-06-20

    The absorption of dietary fat involves the re-esterification of digested triacylglycerol in the enterocytes, a process catalyzed by acyl-CoA:monoacylglycerol acyltransferase (MGAT) 2. Mice without a functional gene encoding MGAT2 (Mogat2(-/-)) are protected from diet-induced obesity. Surprisingly, these mice absorb normal amounts of dietary fat but increase their energy expenditure. MGAT2 is expressed in tissues besides intestine, including adipose tissue in both mice and humans. To test the hypothesis that intestinal MGAT2 regulates systemic energy balance, we generated and characterized mice deficient in MGAT2 specifically in the small intestine (Mogat2(IKO)). We found that, like Mogat2(-/-) mice, Mogat2(IKO) mice also showed a delay in fat absorption, a decrease in food intake, and a propensity to use fatty acids as fuel when first exposed to a high fat diet. Mogat2(IKO) mice increased energy expenditure although to a lesser degree than Mogat2(-/-) mice and were protected against diet-induced weight gain and associated comorbidities, including hepatic steatosis, hypercholesterolemia, and glucose intolerance. These findings illustrate that intestinal lipid metabolism plays a crucial role in the regulation of systemic energy balance and may be a feasible intervention target. In addition, they suggest that MGAT activity in extraintestinal tissues may also modulate energy metabolism. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Untargeted mass spectrometric approach in metabolic healthy offspring of patients with type 2 diabetes reveals medium-chain acylcarnitine as potential biomarker for lipid induced glucose intolerance (LGIT).

    Science.gov (United States)

    Knebel, Birgit; Mack, Susanne; Lehr, Stefan; Barsch, Aiko; Schiller, Martina; Haas, Jutta; Lange, Simone; Fuchser, Jens; Zurek, Gabriela; Müller-Wieland, Dirk; Kotzka, Jorg

    2016-12-01

    Offspring of type 2 diabetes (T2D) patients have increased risk to develop diabetes, due to inherited genetic susceptibility that directly interferes with the individual adaption to environmental conditions. We characterise T2D offspring (OSP) to identify metabolic risk markers for early disease prediction. Plasma of metabolically healthy OSP individuals (n = 43) was investigated after an oral lipid tolerance test (oLTT) by an untargeted mass spectrometric approach for holistic metabolome analyses. Two subgroups of OSP probands can be separated by oLTT, although not differing in general clinical parameters. Analyses of the plasma metabolome revealed mainly medium-chain acylcarnitines and very long-chain fatty acids with differential abundance in the subgroups. The study presented indicates that metabolically healthy OSP of T2D patients differ upon metabolic challenging in serum metabolite composition, especially medium-chain acylcarnitines. The difference suggest that postprandial lipid induced glucose intolerance (LGIT) may serve as a further valuable marker for early diabetes prediction.

  5. Potential probiotic Bifidobacterium animalis ssp. lactis 420 prevents weight gain and glucose intolerance in diet-induced obese mice.

    Science.gov (United States)

    Stenman, L K; Waget, A; Garret, C; Klopp, P; Burcelin, R; Lahtinen, S

    2014-12-01

    Alterations of the gut microbiota and mucosal barrier are linked with metabolic diseases. Our aim was to investigate the potential benefit of the potential probiotic Bifidobacterium animalis ssp. lactis 420 in reducing high-fat diet-induced body weight gain and diabetes in mice. In the obesity model, C57Bl/6J mice were fed a high-fat diet (60 energy %) for 12 weeks, and gavaged daily with B. lactis 420 (109 cfu) or vehicle. In the diabetes model, mice were fed a high-fat, ketogenic diet (72 energy % fat) for 4 weeks, with a 6-week subsequent treatment with B. lactis 420 (108-1010 cfu/day) or vehicle, after which they were analysed for body composition. We also analysed glucose tolerance, plasma lipopolysaccharide and target tissue inflammation using only one of the B. lactis 420 groups (109 cfu/day). Intestinal bacterial translocation and adhesion were analysed in a separate experiment using an Escherichia coli gavage. Body fat mass was increased in both obese (10.7 ± 0.8 g (mean ± standard error of mean) vs. 1.86 ± 0.21 g, Pdiabetic mice (3.01 ± 0.4 g vs. 1.14 ± 0.15 g, Pdiabetic mice (1.89 ± 0.16 g, P=0.02 for highest dose). This was reflected as reduced weight gain and improved glucose tolerance. Furthermore, B. lactis 420 decreased plasma lipopolysaccharide levels (Pdiabetic mice. Reduced intestinal mucosal adherence and plasma lipopolysaccharide suggest a mechanism related to reduced translocation of gut microbes.

  6. Risk of glucose intolerance and gestational diabetes mellitus in relation to maternal habitual snoring during early pregnancy.

    Science.gov (United States)

    Qiu, Chunfang; Lawrence, Wayne; Gelaye, Bizu; Stoner, Lee; Frederick, Ihunnaya O; Enquobahrie, Daniel A; Sorensen, Tanya K; Williams, Michelle A

    2017-01-01

    Obstructive sleep apnea (OSA) or habitual snoring is known to be associated with impaired glucose tolerance and type 2 diabetes among both men and non-pregnant women. We examined the association of habitual snoring during early pregnancy with risk of impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM). A cohort of 1,579 women was interviewed during early pregnancy. We collected information about snoring frequency during early pregnancy. Results from screening and diagnostic tests for IGT and GDM were abstracted from medical records. Multivariate logistic regression models were fitted to estimate odds ratios (OR) and 95% confidence intervals (95% CI) of IGT and GDM associated with snoring in early pregnancy. Overall, women who snored "most or all of the time" had a 2.1-fold increased odds of IGT (OR 2.10; 95% CI 1.31-3.35) and a 2.5-fold increased odds of GDM (OR 2.50; 95% CI 1.34-4.67) as compared with women who never snored. Compared with lean women (pre-pregnancy body mass index (BMI) snore, lean snorers had a 2-fold increased odds of GDM (OR = 1.99, 95% CI: 1.07-3.68). The odds of GDM risk was particularly elevated among overweight women (BMI ≥ 25 kg/m2) who snored (OR = 5.01; 95% CI 2.71-9.26). However, there was no evidence of an interaction between overweight and snoring with GDM risk (p-value = 0.144). These findings, if confirmed, may have important implications for tailoring prenatal care for overweight pregnant women, and /or those with a history of habitual snoring in early pregnancy.

  7. [Lactose intolerance].

    Science.gov (United States)

    Rosado, Jorge L

    2016-09-01

    The most common problem limiting milk consumption worldwide is lactose intolerance (LI), which is defined as the experience of gastrointestinal symptoms due to the intake of lactose-containing food. When symptoms ensue the intake of milk, the condition is referred as milk intolerance, and it may or may not be due to LI. The most common cause of LI is primary lactase deficiency which occurs in 30% of Mexican adults when one glass of milk is consumed (12-18 g of lactose). LI occurs in less than 15% of adults after the intake of this dose of lactose. Another cause of lactose intolerance is due to secondary lactase deficiency, which occurs because lactase is reduced due to diseases that affect the intestinal mucosa. Lactose intolerance can be eliminated or significantly reduced by elimination or reduction of the intake of milk and milk containing products. Recent studies demonstrate that when β-casein-A1 contained in milk is hydrolyzed it produces β-casomorphine-7 which is an opioid associated with milk intolerance.

  8. Segment of rat chromosome 20 regulates diet-induced augmentations in adiposity, glucose intolerance, and blood pressure

    Czech Academy of Sciences Publication Activity Database

    Pausová, Z.; Šedová, L.; Berube, J.; Hamet, P.; Tremblay, J.; Dumont, M.; Gaudet, D.; Pravenec, Michal; Křen, Vladimír; Kuneš, Jaroslav

    2003-01-01

    Roč. 41, č. 5 (2003), s. 1047-1055 ISSN 0194-911X R&D Projects: GA MŠk LN00A079; GA ČR GV204/98/K015 Grant - others:HHMI(US) HHMI55000331; CIHR(CA) MOP-37915; CIHR(CA) MT-14654 Institutional research plan: CEZ:AV0Z5011922 Keywords : SHR * hypertension * insulin resistance Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.630, year: 2003

  9. Secreted factors from dental pulp stem cells improve glucose intolerance in streptozotocin-induced diabetic mice by increasing pancreatic β-cell function.

    Science.gov (United States)

    Izumoto-Akita, Takako; Tsunekawa, Shin; Yamamoto, Akihito; Uenishi, Eita; Ishikawa, Kota; Ogata, Hidetada; Iida, Atsushi; Ikeniwa, Makoto; Hosokawa, Kaori; Niwa, Yasuhiro; Maekawa, Ryuya; Yamauchi, Yuichiro; Seino, Yusuke; Hamada, Yoji; Hibi, Hideharu; Arima, Hiroshi; Ueda, Minoru; Oiso, Yutaka

    2015-01-01

    Many studies have reported that stem cell transplantation promotes propagation and protection of pancreatic β-cells in streptozotocin (STZ)-induced diabetic mice without the differentiation of transplanted cells into pancreatic β-cells, suggesting that the improvement is due to a paracrine effect of the transplanted cells. We investigated the effects of factors secreted by dental pulp stem cells from human exfoliated deciduous teeth (SHED) on β-cell function and survival. Conditioned medium from SHED (SHED-CM) was collected 48 h after culturing in serum-free Dulbecco's modified Eagle's medium (DMEM). The insulin levels in SHED-CM and serum-free conditioned media from human bone marrow-derived mesenchymal stem cells (BM-CM) were undetectable. STZ-induced diabetic male C57B/6J mice were injected with DMEM as a control, SHED-CM, exendin-4 (Ex-4), or BM-CM for 14 days. Mouse pancreatic β-cell line MIN6 cells were incubated with different concentrations of STZ with SHED-CM, DMEM, Ex-4, or BM-CM for 6 h. Administration of 1 mL of SHED-CM twice a day improved glucose intolerance in STZ-induced diabetic mice and the effect continued for 20 days after the end of treatment. SHED-CM treatment increased pancreatic insulin content and β-cell mass through proliferation and an intraperitoneal glucose tolerance test revealed enhanced insulin secretion. Incubation of MIN6 cells (a mouse pancreatic β-cell line) with SHED-CM enhanced insulin secretion in a glucose concentration-dependent manner and reduced STZ-induced cell death, indicating that the amelioration of hyperglycemia was caused by the direct effects of SHED-CM on β-cell function and survival. These effects were more pronounced than with the use of Ex-4, a conventional incretin-based drug, and BM-CM, which is a medium derived from other stem cells. These findings suggest that SHED-CM provides direct protection and encourages the propagation of β-cells, and has potential as a novel strategy for treatment

  10. FoxO1 gain of function in the pancreas causes glucose intolerance, polycystic pancreas, and islet hypervascularization.

    Directory of Open Access Journals (Sweden)

    Osamu Kikuchi

    Full Text Available Genetic studies revealed that the ablation of insulin/IGF-1 signaling in the pancreas causes diabetes. FoxO1 is a downstream transcription factor of insulin/IGF-1 signaling. We previously reported that FoxO1 haploinsufficiency restored β cell mass and rescued diabetes in IRS2 knockout mice. However, it is still unclear whether FoxO1 dysregulation in the pancreas could be the cause of diabetes. To test this hypothesis, we generated transgenic mice overexpressing constitutively active FoxO1 specifically in the pancreas (TG. TG mice had impaired glucose tolerance and some of them indeed developed diabetes due to the reduction of β cell mass, which is associated with decreased Pdx1 and MafA in β cells. We also observed increased proliferation of pancreatic duct epithelial cells in TG mice and some mice developed a polycystic pancreas as they aged. Furthermore, TG mice exhibited islet hypervascularities due to increased VEGF-A expression in β cells. We found FoxO1 binds to the VEGF-A promoter and regulates VEGF-A transcription in β cells. We propose that dysregulation of FoxO1 activity in the pancreas could account for the development of diabetes and pancreatic cysts.

  11. Oral salmon calcitonin protects against impaired fasting glycemia, glucose intolerance, and obesity induced by high-fat diet and ovariectomy in rats.

    Science.gov (United States)

    Feigh, Michael; Andreassen, Kim V; Hjuler, Sara T; Nielsen, Rasmus H; Christiansen, Claus; Henriksen, Kim; Karsdal, Morten A

    2013-07-01

    Oral salmon calcitonin (sCT) has demonstrated clinical efficacy in treating osteoporosis in postmenopausal women. The postmenopausal state is also associated with obesity-related insulin resistance (IR) and type 2 diabetes. The aim of this study was to investigate the preventive effects of oral sCT on energy and glucose homeostasis in high-fat diet (HFD)- and ovariectomy (OVX)-induced obese rats. Furthermore, the weight-regulatory and gluco-regulatory effects of short-term oral sCT intervention on HFD-induced obese rats were explored. For prevention, female rats exposed to HFD with or without OVX were treated with oral sCT for 5 weeks. As intervention, HFD-induced obese male rats were treated with oral sCT for 4 days. Body weight, food intake, and plasma glucose, insulin, and leptin levels were measured, and the clinical homeostasis model assessment for insulin resistance (HOMA-IR) index was calculated. In addition, oral glucose tolerance was evaluated in the systemic and portal circulations. For prevention, oral sCT reduced body weight by ∼16% to 19% (P fasting glycemia (P obesity. Furthermore, oral sCT significantly reduced the incremental area under the curve for plasma glucose and insulin by ∼40% and ∼70%, respectively, during glucose tolerance testing. As intervention in HFD-induced obese rats, oral sCT reduced body weight, fasting glycemia, and insulinemia in conjunction with HOMA-IR (P obese rats, indicating the clinical usefulness of oral sCT in postmenopausal obesity-related IR and type 2 diabetes.

  12. Consumption of Honey, Sucrose, and High-Fructose Corn Syrup Produces Similar Metabolic Effects in Glucose-Tolerant and -Intolerant Individuals.

    Science.gov (United States)

    Raatz, Susan K; Johnson, LuAnn K; Picklo, Matthew J

    2015-10-01

    Public health recommendations call for a reduction in added sugars; however, controversy exists over whether all nutritive sweeteners produce similar metabolic effects. The objective was to compare the effects of the chronic consumption of 3 nutritive sweeteners [honey, sucrose, and high-fructose corn syrup containing 55% fructose (HFCS55)] on circulating glucose, insulin, lipids, and inflammatory markers; body weight; and blood pressure in individuals with normal glucose tolerance (GT) and those with impaired glucose tolerance (IGT). In a crossover design, participants consumed daily, in random order, 50 g carbohydrate from assigned sweeteners for 2 wk with a 2- to 4-wk washout period between treatments. Participants included 28 GT and 27 IGT volunteers with a mean age of 38.9 ± 3.6 y and 52.1 ± 2.7 y, respectively, and a body mass index (in kg/m(2)) of 26 ± 0.8 and 31.5 ± 1.0, respectively. Body weight, blood pressure (BP), serum inflammatory markers, lipids, fasting glucose and insulin, and oral-glucose-tolerance tests (OGTTs) were completed pre- and post-treatment. The OGTT incremental areas under the curve (iAUCs) for glucose and insulin were determined and homeostasis model assessment of insulin resistance (HOMA-IR) scores were calculated. Body weight and serum glucose, insulin, inflammatory markers, and total and LDL-cholesterol concentrations were significantly higher in the IGT group than in the GT group at baseline. Glucose, insulin, HOMA-IR, and the OGTT iAUC for glucose or insulin did not differ by treatment, but all responses were significantly higher in the IGT group compared with the GT group. Body weight was unchanged by treatment. Systolic BP was unchanged, whereas diastolic BP was significantly lower in response to sugar intake across all treatments. An increase in high-sensitivity C-reactive protein (hsCRP) was observed in the IGT group in response to all sugars. No treatment effect was observed for interleukin 6. HDL cholesterol did not

  13. Lactose Intolerance

    Science.gov (United States)

    ... A health care provider will tell the patient what foods or medications to avoid before the test. • Stool ... and www.nccam.nih.gov. 7  Lactose Intolerance What products contain lactose? Lactose is present in many food products and in some medications. Food Products Lactose ...

  14. A unified definition of clinical resistance/intolerance to hydroxyurea in essential thrombocythemia

    DEFF Research Database (Denmark)

    Barosi, G; Besses, C; Birgegard, G

    2007-01-01

    -reactivity between wheat and grass pollen was studied by blot inhibition. RESULTS: The most important wheat allergens were the alpha-amylase/trypsin inhibitor subunits, which were present in all three protein fractions of raw and cooked wheat. Other important allergens were a 9-kDa LTP in the albumin....../globulin fraction and several low-molecular-weight (LMW) glutenin subunits in the gluten fraction. All these allergens showed heat resistance and lack of cross-reactivity to grass pollen allergens. LTP was a major allergen only in Italian patients. CONCLUSIONS: The alpha-amylase inhibitor was confirmed...

  15. Nilotinib: optimal therapy for patients with chronic myeloid leukemia and resistance or intolerance to imatinib

    Directory of Open Access Journals (Sweden)

    Ronan Swords

    2009-03-01

    Full Text Available Ronan Swords, Devalingam Mahalingam, Swaminathan Padmanabhan, Jennifer Carew, Francis GilesInstitute for Drug Development, Cancer Therapy and Research Centre, University of Texas Health Science Centre at San Antonio, USAAbstract: Chronic myeloid leukemia (CML is the consequence of a single balanced translocation that produces the BCR-ABL fusion oncogene which is detectable in over 90% of patients at presentation. The BCR-ABL inhibitor imatinib mesylate (IM has improved survival in all phases of CML and is the standard of care for newly diagnosed patients in chronic phase. Despite the very significant therapeutic benefits of IM, a small minority of patients with early stage disease do not benefit optimally while IM therapy in patients with advanced disease is of modest benefit in many. Diverse mechanisms may be responsible for IM failures, with point mutations within the Bcr-Abl kinase domain being amongst the most common resistance mechanisms described in patients with advanced CML. The development of novel agents designed to overcome IM resistance, while still primarily targeted on BCR-ABL, led to the creation of the high affinity aminopyrimidine inhibitor, nilotinib. Nilotinib is much more potent as a BCR-ABL inhibitor than IM and inhibits both wild type and IM-resistant BCR-ABL with significant clinical activity across the entire spectrum of BCR-ABL mutants with the exception of T315I. The selection of a second generation tyrosine kinase inhibitor to rescue patients with imatinib failure will be based on several factors including age, co-morbid medical problems and ABL kinase mutational profile. It should be noted that while the use of targeted BCR-ABL kinase inhibitors in CML represents a paradigm shift in CML management these agents are not likely to have activity against the quiescent CML stem cell pool. The purpose of this review is to summarize the pre-clinical and clinical data on nilotinib in patients with CML who have failed prior

  16. Effects of Noise Exposure on Systemic and Tissue-Level Markers of Glucose Homeostasis and Insulin Resistance in Male Mice.

    Science.gov (United States)

    Liu, Lijie; Wang, Fanfan; Lu, Haiying; Cao, Shuangfeng; Du, Ziwei; Wang, Yongfang; Feng, Xian; Gao, Ye; Zha, Mingming; Guo, Min; Sun, Zilin; Wang, Jian

    2016-09-01

    Epidemiological studies have indicated that noise exposure is associated with an increased risk of type 2 diabetes mellitus (T2DM). However, the nature of the connection between noise exposure and T2DM remains to be explored. We explored whether and how noise exposure affects glucose homeostasis in mice as the initial step toward T2DM development. Male ICR mice were randomly assigned to one of four groups: the control group and three noise groups (N20D, N10D, and N1D), in which the animals were exposed to white noise at 95 decibel sound pressure level (dB SPL) for 4 hr per day for 20 successive days, 10 successive days, or 1 day, respectively. Glucose tolerance and insulin sensitivity were evaluated 1 day, 1 week, and 1 month after the final noise exposure (1DPN, 1WPN, and 1MPN). Standard immunoblots, immunohistochemical methods, and enzyme-linked immunosorbent assays (ELISA) were performed to assess insulin signaling in skeletal muscle, the morphology of β cells, and plasma corticosterone levels. Noise exposure for 1 day caused transient glucose intolerance and insulin resistance, whereas noise exposure for 10 and 20 days had no effect on glucose tolerance but did cause prolonged insulin resistance and an increased insulin response to glucose challenge. Akt phosphorylation and GLUT4 translocation in response to exogenous insulin were decreased in the skeletal muscle of noise-exposed animals. Noise exposure at 95 dB SPL caused insulin resistance in male ICR mice, which was prolonged with longer noise exposure and was likely related to the observed blunted insulin signaling in skeletal muscle. Liu L, Wang F, Lu H, Cao S, Du Z, Wang Y, Feng X, Gao Y, Zha M, Guo M, Sun Z, Wang J. 2016. Effects of noise exposure on systemic and tissue-level markers of glucose homeostasis and insulin resistance in male mice. Environ Health Perspect 124:1390-1398; http://dx.doi.org/10.1289/EHP162.

  17. Triglycerides and glucose index: a useful indicator of insulin resistance.

    Science.gov (United States)

    Unger, Gisela; Benozzi, Silvia Fabiana; Perruzza, Fernando; Pennacchiotti, Graciela Laura

    2014-12-01

    Insulin resistance assessment requires sophisticated methodology of difficult application. Therefore, different estimators for this condition have been suggested. The aim of this study was to evaluate the triglycerides and glucose (TyG) index as a marker of insulin resistance and to compare it to the triglycerides/HDL cholesterol ratio (TG/HDL-C), in subjects with and without metabolic syndrome (MS). An observational, cross-sectional study was conducted on 525 adults of a population from Bahia Blanca, Argentina, who were divided into two groups: with MS (n=89) and without MS (n=436). The discriminating capacities for MS of the TyG index, calculated as Ln (TG [mg/dL] x glucose [mg/dL]/2), and the TG/HDL-C ratio were evaluated. Pre-test probability for MS was 30%. The mean value of the TyG index was higher in the group with MS as compared to the group without MS and its correlation with the TG/HDL-C ratio was good. The cut-off values for MS in the overall population were 8.8 for the TyG index (sensitivity=79%, specificity=86%), and 2.4 for the TG/HDL-C ratio (sensitivity=88%, specificity=72%). The positive likelihood ratios and post-test probabilities for these parameters were 5.8 vs 3.1 and 72% vs 58% respectively. The cut-off point for the TyG index was 8.8 in men and 8.7 in women; the respective values for TG/C-HDL were 3.1 in men and 2.2 in women. The TyG index was a good discriminant of MS. Its simple calculation warrants its further study as an alternative marker of insulin resistance. Copyright © 2014 SEEN. Published by Elsevier Espana. All rights reserved.

  18. A Study on the Glucose and Immunoreactive Insulin Response during Oral Glucose Tolerance Test in Patients with Chronic Liver Diseases

    International Nuclear Information System (INIS)

    Choe, Kang Won; Lee, Hong Kyu; Koh, Chang Soon; Lee, Mu Ho

    1973-01-01

    The blood glucose and plasma immunoreactive insulin (IRI) levels were measured during aral glucose tolerance test in 7 healthy subjects and 6 patients with chronic liver diseases. The glucose tolerance was impaired in 5 of the 6 patients and normal in I. Plasma IRI responses were markedly increased and delayed in all patients, suggesting endogenous insulin resistance. Patients with more glucose intolerance showed less increase in plasma IRI than the group with less intolerance. lt is suggested that some insulin antagonists may decrease the peripheral insulin sensitivity and stimulate compensatory hyperactivity of pancreatic islets. If the compensatory hyperactivity is inadequate due to gemetic predisposition to diabetes mellitus or exhaustion of β-cells of pancreatic islets, the glucose intolerance and overt diabetes mellitus may ensue.

  19. Insulin resistance and glucose levels in subjects with subclinical hypothyroidism

    International Nuclear Information System (INIS)

    Kahn, S.H.; Fazal, N.; Yasir, M.; Asif, N.; Rafi, T.

    2017-01-01

    To compare insulin resistance and glycemic indicators among subjects with euthyroidism and subclinical hypothyroidism. Study Design: Comparative cross-sectional study. Place and Duration of Study: Department of Pathology and Medicine, PNS Hafeez, Islamabad, in collaboration with the Department of Chemical Pathology and Endocrinology at the Armed Forces Institute of Pathology (AFIP), Rawalpindi, from December 2015 to September 2016. Methodology: Subjects referred for executive screening of apparently healthy population (without any known history of diabetes, hypertension, heart disease or other chronic ailments), were included. Subjects were grouped as euthyroidism and subclinical hypothyroidism. Results: Median (IQR) insulin resistance indices including fasting insulin and Homeostasis Model Assessment for Insulin Resistance in subjects with group-1 (n=176, 87%, Thyroid Stimulating Hormone: 0.5 - 3.5 mIU/L) and group-2 (n=26, 13%, Thyroid Stimulating Hormone: 3.51 - 15 mIU/L) were 7.6 (6.70) vs. 11.4 (13.72, p=0.040) and 1.77 (1.79) vs. 2.8 (3.07, p=0.071). The median differences for fasting plasma glucose were 5.0 (1.0) in group-1 vs. 5.0 (1.47) for Group-2 [p=0.618], and glycated hemoglobin was 5.60 (1.1) vs. 5.60 (1.7, p=0.824). Homeostasis Model Assessment for beta sensitivity index in paradox showed slightly higher values for group-2 [median (IQR) 86.67 (92.94)] than group-1 [111.6 (189.64, p= 0.040)]. Conclusion: Measures of insulin resistance including Homeostasis Model Assessment for Insulin Resistance and fasting insulin levels were significantly different between subjects with euthyroidism and having subclinical hypothyroidism. (author)

  20. Chemical intolerance

    DEFF Research Database (Denmark)

    Dantoft, Thomas Meinertz; Andersson, Linus; Nordin, Steven

    2015-01-01

    Chemical intolerance (CI) is a term used to describe a condition in which the sufferer experiences a complex array of recurrent unspecific symptoms attributed to low-level chemical exposure that most people regard as unproblematic. Severe CI constitutes the distinguishing feature of multiple...... chemical sensitivity (MCS). The symptoms reported by CI subjects are manifold, involving symptoms from multiple organs systems. In severe cases of CI, the condition can cause considerable life-style limitations with severe social, occupational and economic consequences. As no diagnostic tools for CI...

  1. T-lymphocyte responses to intestinally absorbed antigens can contribute to adipose tissue inflammation and glucose intolerance during high fat feeding.

    Directory of Open Access Journals (Sweden)

    Yuehui Wang

    Full Text Available BACKGROUND: Obesity is associated with inflammation of visceral adipose tissues, which increases the risk for insulin resistance. Animal models suggest that T-lymphocyte infiltration is an important early step, although it is unclear why these cells are attracted. We have recently demonstrated that dietary triglycerides, major components of high fat diets, promote intestinal absorption of a protein antigen (ovalbumin, "OVA". The antigen was partly transported on chylomicrons, which are prominently cleared in adipose tissues. We hypothesized that intestinally absorbed gut antigens may cause T-lymphocyte associated inflammation in adipose tissue. METHODOLOGY/PRINCIPAL FINDINGS: Triglyceride absorption promoted intestinal absorption of OVA into adipose tissue, in a chylomicron-dependent manner. Absorption tended to be higher in mesenteric than subcutaneous adipose tissue, and was lowest in gonadal tissue. OVA immunoreactivity was detected in stromal vascular cells, including endothelial cells. In OVA-sensitized mice, OVA feeding caused marked accumulation of CD3+ and osteopontin+ cells in mesenteric adipose tissue. The accumulating T-lymphocytes were mainly CD4+. As expected, high-fat (60% kCal diets promoted mesenteric adipose tissue inflammation compared to low-fat diets (10% Kcal, as reflected by increased expression of osteopontin and interferon-gamma. Immune responses to dietary OVA further increased diet-induced osteopontin and interferon-gamma expression in mesenteric adipose. Inflammatory gene expression in subcutaneous tissue did not respond significantly to OVA or dietary fat content. Lastly, whereas OVA responses did not significantly affect bodyweight or adiposity, they significantly impaired glucose tolerance. CONCLUSIONS/SIGNIFICANCE: Our results suggest that loss or lack of immunological tolerance to intestinally absorbed T-lymphocyte antigens can contribute to mesenteric adipose tissue inflammation and defective glucose metabolism

  2. Glucose uptake in human brown adipose tissue is impaired upon fasting-induced insulin resistance.

    Science.gov (United States)

    Hanssen, Mark J W; Wierts, Roel; Hoeks, Joris; Gemmink, Anne; Brans, Boudewijn; Mottaghy, Felix M; Schrauwen, Patrick; van Marken Lichtenbelt, Wouter D

    2015-03-01

    Human brown adipose tissue (BAT) has recently emerged as a potential target in the treatment of type 2 diabetes, owing to its capacity to actively clear glucose from the circulation—at least upon cold exposure. The effects of insulin resistance on the capacity of human BAT to take up glucose are unknown. Prolonged fasting is known to induce insulin resistance in peripheral tissues in order to spare glucose for the brain. We studied the effect of fasting-induced insulin resistance on the capacity of BAT to take up glucose during cold exposure as well as on cold-stimulated thermogenesis. BAT glucose uptake was assessed by means of cold-stimulated dynamic 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography/computed tomography ([(18)F]FDG-PET/CT) imaging. We show that a 54 h fasting period markedly decreases both cold-induced BAT glucose uptake and nonshivering thermogenesis (NST) during cold stimulation. In vivo molecular imaging and modelling revealed that the reduction of glucose uptake in BAT was due to impaired cellular glucose uptake and not due to decreased supply. Interestingly, decreased BAT glucose uptake upon fasting was related to a decrease in core temperature during cold exposure, pointing towards a role for BAT in maintaining normothermia in humans. Cold-stimulated glucose uptake in BAT is strongly reduced upon prolonged fasting. When cold-stimulated glucose uptake in BAT is also reduced under other insulin-resistant states, such as diabetes, cold-induced activation of BAT may not be a valid way to improve glucose clearance by BAT under such conditions. www.trialregister.nl NTR3523 FUNDING: This work was supported by the EU FP7 project DIABAT (HEALTH-F2-2011-278373 to WDvML) and by the Netherlands Organization for Scientific Research (TOP 91209037 to WDvML).

  3. Prevalence of impaired glucose tolerance and insulin resistance among obese children and adolescents

    Directory of Open Access Journals (Sweden)

    Robabeh Ghergherechi

    2010-07-01

    Full Text Available Robabeh Ghergherechi1, Ali Tabrizi21Department of Pediatrics Endocrinology, Tabriz University of Medical Sciences, Tabriz, Iran; 2Students’ Research Committee, Tabriz University of Medical Sciences, Tabriz, IranPurpose: Obesity is one of the most important nutritional disorders in the world which has an obvious relationship with the incidence of metabolic diseases. Obesity prevalence has increased among children and adolescents during recent decades, leading to a rise in Type 2 diabetes mellitus (DM II prevalence in these two age brackets. Hence, the aim of this study was to assess impaired glucose tolerance and insulin resistance, and gather metabolic findings in obese children and adolescents.Methods and materials: We studied 110 obese children and adolescents (body mass index > 95th percentile for age and gender 4–18 years of age referred to the endocrine clinic of the Children’s Hospital at Tabriz University in a descriptive cross-sectional study. ­Fasting glucose, insulin, and lipid profile in all subjects were determined. Oral glucose tolerance test after eating 75 g/kg glucose was performed. Homeostatic model assessment was used to ­estimate insulin resistance.Results: Impaired glucose tolerance and insulin resistance prevalence in 68 obese adolescents was 14.7% and 31.8%, respectively. Impaired glucose tolerance and insulin resistance was not seen in 23.8% of 42 obese children. No case of DM II was seen. There was a significant statistical difference in glucose (P = 0.003 and insulin (P < 0.001 level at minute 120 in individuals with impaired glucose tolerance compared to obese children and adolescents without impaired glucose tolerance. Rate of insulin resistance in patients with impaired glucose tolerance was greater and had a significant statistical difference (P = 0.03.Conclusion: Obesity has a close relationship with increased risk of impaired glucose tolerance and insulin resistance in children and adolescents. Oral glucose

  4. Adult-onset deficiency of acyl CoA:monoacylglycerol acyltransferase 2 protects mice from diet-induced obesity and glucose intolerance.

    Science.gov (United States)

    Banh, Taylor; Nelson, David W; Gao, Yu; Huang, Ting-Ni; Yen, Mei-I; Yen, Chi-Liang E

    2015-02-01

    Acyl-CoA:monoacylglycerol acyltransferase (MGAT) 2 catalyzes triacylglycerol (TAG) synthesis, required in intestinal fat absorption. We previously demonstrated that mice without a functional MGAT2-coding gene (Mogat2(-/-)) exhibit increased energy expenditure and resistance to obesity induced by excess calories. One critical question raised is whether lacking MGAT2 during early development is required for the metabolic phenotypes in adult mice. In this study, we found that Mogat2(-/-) pups grew slower than wild-type littermates during the suckling period. To determine whether inactivating MGAT2 in adult mice is sufficient to confer resistance to diet-induced obesity, we generated mice with an inducible Mogat2-inactivating mutation. Mice with adult-onset MGAT2 deficiency (Mogat2(AKO)) exhibited a transient decrease in food intake like Mogat2(-/-) mice when fed a high-fat diet and a moderate increase in energy expenditure after acclimatization. They gained less weight than littermate controls, but the difference was smaller than that between wild-type and Mogat2(-/-) mice. The moderate reduction in weight gain was associated with reduced hepatic TAG and improved glucose tolerance. Similar protective effects were also observed in mice that had gained weight on a high-fat diet before inactivating MGAT2. These findings suggest that adult-onset MGAT2 deficiency mitigates metabolic disorders induced by high-fat feeding and that MGAT2 modulates early postnatal nutrition and may program metabolism later in life. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

  5. Influence of resistance exercise training on glucose control in women with type 2 diabetes.

    Science.gov (United States)

    Fenicchia, L M; Kanaley, J A; Azevedo, J L; Miller, C S; Weinstock, R S; Carhart, R L; Ploutz-Snyder, L L

    2004-03-01

    The objective of the study was to evaluate the effects of acute and chronic resistance training on glucose and insulin responses to a glucose load in women with type 2 diabetes. Subjects consisted of type 2 diabetic women (n = 7) and age-matched controls (n = 8) with normal glucose tolerance. All subjects participated in 3 oral glucose tolerance tests: pretraining, 12 to 24 hours after the first exercise session (acute) and 60 to 72 hours after the final training session (chronic). Exercise training consisted of a whole body resistance exercise program using weight-lifting machines 3 days per week for 6 weeks. Resistance training was effective in increasing strength of all muscle groups in all subjects. Integrated glucose concentration expressed as area under the curve (AUC) was 3,355.0 +/- 324.6 mmol/L. min pretraining, improved significantly (P benefits, individuals must follow a regular schedule that includes daily exercise.

  6. Glucose modulation induces reactive oxygen species and increases P-glycoprotein-mediated multidrug resistance to chemotherapeutics

    Science.gov (United States)

    Seebacher, N A; Richardson, D R; Jansson, P J

    2015-01-01

    Background and Purpose Cancer cells develop resistance to stress induced by chemotherapy. In tumours, a considerable glucose gradient exists, resulting in stress. Notably, hypoxia-inducible factor-1 (HIF-1) is a redox-sensitive transcription factor that regulates P-glycoprotein (Pgp), a crucial drug-efflux transporter involved in multidrug resistance (MDR). Here, we investigated how glucose levels regulate Pgp-mediated drug transport and resistance. Experimental Approach Human tumour cells (KB31, KBV1, A549 and DMS-53) were incubated under glucose starvation to hyperglycaemic conditions. Flow cytometry assessed reactive oxygen species (ROS) generation and Pgp activity. HIF-1α, NF-κB and Pgp expression were assessed by reverse transcriptase-PCR and Western blotting. Fluorescence microscopy examined p65 distribution and a luciferase-reporter assay assessed HIF-1 promoter-binding activity. The effect of glucose-induced stress on Pgp-mediated drug resistance was examined after incubating cells with the chemotherapeutic and Pgp substrate, doxorubicin (DOX), and performing MTT assays validated by viable cell counts. Key Results Changes in glucose levels markedly enhanced cellular ROS and conferred Pgp-mediated drug resistance. Low and high glucose levels increased (i) ROS generation via NADPH oxidase 4 and mitochondrial membrane destabilization; (ii) HIF-1 activity; (iii) nuclear translocation of the NF-κB p65 subunit; and (iv) HIF-1α mRNA and protein levels. Increased HIF-1α could also be due to decreased prolyl hydroxylase protein under these conditions. The HIF-1α target, Pgp, was up-regulated at low and high glucose levels, which led to lower cellular accumulation of Pgp substrate, rhodamine123, and greater resistance to DOX. Conclusions and Implications As tumour cells become glucose-deprived or exposed to high glucose levels, this increases stress, leading to a more aggressive MDR phenotype via up-regulation of Pgp. PMID:25586174

  7. Effects of turtle oil on insulin sensitivity and glucose metabolism in insulin resistant cell model

    International Nuclear Information System (INIS)

    Bai Jing; Tian Yaping; Guo Duo

    2007-01-01

    To evaluate the effects of turtle oil on insulin sensitivity and glucose metabolism in an insulin-resistant (IR) cell model which was established by the way of high concentration of insulin induction with HepG 2 cell in vitro culture. The IR cells were treated by turtle oil, the glucose consumption and 3 H-D-glucose incorporation rate in IR cells were detected by the way of glucose oxidase and 3 H-D-glucose incorporation assay respectively. The state of cell proliferation was tested by MTT method. The results showed that the incorporation rate of 3 H-D-glucose in IR cells was significantly lower than that in the control cells(P 3 H-D-glucose incorporation rate in either IR cells or control cells was increased with the increase of insulin concentration. Moreover, the 3 H-D-glucose incorporation rate of IR cells increased slower than that of control cells. The MTT assay showed that turtle oil can promote the proliferation of IR cell and control cell. The glucose uptake and glucose consumption in IR cell which treated with turtle oil was significantly increase than that in the control cells (P<0.05). Turtle oil can improve the insulin sensitivity and glucose metabolism in the IR cell model. (authors)

  8. Insulin-stimulated glucose uptake in healthy and insulin-resistant skeletal muscle

    DEFF Research Database (Denmark)

    Deshmukh, Atul S

    2016-01-01

    transporter protein 4 (GLUT4) to the plasma membrane which leads to facilitated diffusion of glucose into the cell. Understanding the precise signaling events guiding insulin-stimulated glucose uptake is pivotal, because impairment in these signaling events leads to development of insulin resistance and type...... 2 diabetes. This review summarizes current understanding of insulin signaling pathways mediating glucose uptake in healthy and insulin-resistant skeletal muscle.......Skeletal muscle is the largest tissues in the human body and is considered the primary target for insulin-stimulated glucose disposal. In skeletal muscle, binding of the insulin to insulin receptor (IR) initiates a signaling cascade that results in the translocation of the insulin-sensitive glucose...

  9. Phase I Study of INNO-406, a Dual Abl/Lyn Kinase Inhibitor, in Philadelphia Chromosome-Positive Leukemias Post-Imatinib Resistance or Intolerance

    Science.gov (United States)

    Kantarjian, H.; le Coutre, P.; Cortes, J.; Pinilla-Ibarz, J.; Nagler, A.; Hochhaus, A.; Kimura, S.; Ottmann, O.

    2010-01-01

    BACKGROUND INNO-406, an oral dual Abl/Lyn tyrosine kinase inhibitor (TKI), demonstrates specific Lyn kinase activity with no or limited activity against other Src-family member kinases. Several Bcr-Abl kinase domain mutations are sensitive to INNO-406 in vitro, including the F317L and F317V mutations. In this study, we evaluated INNO-406 in Philadelphia (Ph) chromosome–positive chronic myelogenous leukemia (CML) or acute lymphocytic leukemia (ALL) post-imatinib resistance or intolerance. METHODS A dose escalation study was conducted with a starting dose of 30mg administered orally once daily. Cohorts of at least 3 patients were treated at each dose level until the maximum tolerated dose (MTD) was reached. Twice-daily (BID) dosing was also evaluated. Therapy was allowed for a maximum of 24 months. RESULTS INNO-406 was administered to 56 patients with imatinib resistance (n=40) or intolerance (n=16). Other previous treatments included nilotinib (n=20), dasatinib (n=26), and dasatinib/nilotinib (n=9). Common mutations upon study entry included Y253H (n=6), G250E (n=4), T315I (n=4) and F317L (n=3). Among 31 patients with CML in chronic phase treated with INNO-406, the major cytogenetic response rate was 19%. In this study, no responses were seen in patients with CML-AP, CML-BP, or Ph-positive ALL. Dose-limiting toxicities (DLTs) at INNO-406 480mg BID were liver function abnormalities and thrombocytopenia. CONCLUSIONS INNO-406 showed anti-CML efficacy in this heavily pretreated study population. Based on the classical determinations of both DLT and MTD, the recommended phase 2 dose of INNO-406 is 240mg orally BID. Lower doses of INNO-406 may be equally effective and should be explored. PMID:20310049

  10. Suspension Trauma / Orthostatic Intolerance

    Science.gov (United States)

    ... Technology Assessment Printer Friendly Version Suspension Trauma/Orthostatic Intolerance Safety and Health Information Bulletin SHIB 03-24- ... with important information about the hazards of orthostatic intolerance and suspension trauma when using fall arrest systems. ...

  11. Hereditary fructose intolerance

    Science.gov (United States)

    Fructosemia; Fructose intolerance; Fructose aldolase B-deficiency; Fructose-1, 6-bisphosphate aldolase deficiency ... substances build up in the liver. Hereditary fructose intolerance is inherited, which means it can be passed ...

  12. Lactose Intolerance (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Lactose Intolerance KidsHealth / For Parents / Lactose Intolerance What's in ... Print en español Intolerancia a la lactosa About Lactose Intolerance For many kids, an ice cream sundae ...

  13. Growth hormone receptor antagonist transgenic mice are protected from hyperinsulinemia and glucose intolerance despite obesity when placed on a HF diet.

    Science.gov (United States)

    Yang, Tianxu; Householder, Lara A; Lubbers, Ellen R; List, Edward O; Troike, Katie; Vesel, Clare; Duran-Ortiz, Silvana; Kopchick, John J; Berryman, Darlene E

    2015-02-01

    Reduced GH levels have been associated with improved glucose metabolism and increased longevity despite obesity in multiple mouse lines. However, one mouse line, the GH receptor antagonist (GHA) transgenic mouse, defies this trend because it has reduced GH action and increased adiposity, but glucose metabolism and life span are similar to controls. Slight differences in glucose metabolism and adiposity profiles can become exaggerated on a high-fat (HF) diet. Thus, in this study, male and female GHA and wild-type (WT) mice in a C57BL/6 background were placed on HF and low-fat (LF) diets for 11 weeks, starting at 10 weeks of age, to assess how GHA mice respond to additional metabolic stress of HF feeding. On a HF diet, all mice showed significant weight gain, although GHA gained weight more dramatically than WT mice, with males gaining more than females. Most of this weight gain was due to an increase in fat mass with WT mice increasing primarily in the white adipose tissue perigonadal depots, whereas GHA mice gained in both the sc and perigonadal white adipose tissue regions. Notably, GHA mice were somewhat protected from detrimental glucose metabolism changes on a HF diet because they had only modest increases in serum glucose levels, remained glucose tolerant, and did not develop hyperinsulinemia. Sex differences were observed in many measures with males reacting more dramatically to both a reduction in GH action and HF diet. In conclusion, our findings show that GHA mice, which are already obese, are susceptible to further adipose tissue expansion with HF feeding while remaining resilient to alterations in glucose homeostasis.

  14. [Fasting insulinemie levels and after overload with oral glucose in overweight children (author's transl)].

    Science.gov (United States)

    López, M J; Colomer, J; Borrajo, E; Alpera, R

    1978-02-01

    Fasting insulinemie levels and after overload with oral glucose are studied in a group of 30 overweight children aged between 2--12 years. The results are: An increase in insulin secretion according to the age only in the overload test. The insulin and glucose areas in the overweight child is statistically bigger than in the healthy child. We conclude that hyperinsulinism in obesity, may be related with a insuline-resistance and with some kind of glucose intolerance.

  15. Assessment of glucose, triglycerides and insulin resistance in ...

    African Journals Online (AJOL)

    Background: Malnutrition remains a significant but intriguing consequence of Human immunodeficiency virus (HIV) infection. Besides factors such as decreased food intake and malabsorption, Human immunodeficiency virus infection is typically associated with adverse metabolic events. Aim: We examine the glucose; ...

  16. The lipid accumulation product for the early prediction of gestational insulin resistance and glucose dysregulation.

    Science.gov (United States)

    Brisson, Diane; Perron, Patrice; Kahn, Henry S; Gaudet, Daniel; Bouchard, Luigi

    2013-04-01

    Recent insights linking insulin resistance and lipid overaccumulation suggest a novel approach for the early identification of women who may soon experience glucose dysregulation. Among women without a history of gestational diabetes, we tested the association between the lipid accumulation product (LAP) obtained in early pregnancy and glucose dysregulation or insulin resistance in the second trimester. A total of 180 white pregnant women of French-Canadian origin were included in this study. At 11–14 weeks' gestation, fasting insulin, glucose, C-peptide concentrations, and estimated insulin resistance (HOMA-IR) were obtained. The waist circumference (WC) and fasting triglycerides (TG) were measured to calculate LAP as(WC[cm] - 58) · TG[mmol/L]. At 24–28 weeks' gestation, glucose was measured 2 hours after a 75-g oral glucose challenge and other fasting variables were repeated. Among the nulliparous women tested at the end of the second trimester, fasting insulin, C-peptide, insulin resistance (HOMA-IR index), fasting glucose, and 2-hour glucose progressively increased ( p £ 0.002)according to their first-trimester LAP tertiles. Similar results were observed in parous women except for the glucose variables. The first-trimester LAP tended to show a stronger correlation to the second-trimester HOMAIR index (r = 0.56) than fasting triglyceride levels alone (r = 0.40) or waist circumference alone (r = 0.44) among nulliparous women. Similar associations were observed for parous women. Adjustment for body mass index weakened these associations, especially among parous women. An increased value of LAP at the beginning of a pregnancy could be associated with an increased risk of insulin resistance or hyperglycemia later in gestation.

  17. Long-term effects of fluoxetine on glycemic control in obese patients with non-insulin-dependent diabetes mellitus or glucose intolerance

    DEFF Research Database (Denmark)

    Breum, Leif; Bjerre, U; Bak, J F

    1995-01-01

    Fluoxetine (F) is a specific serotonin-reuptake inhibitor that has been shown to promote weight loss and improve glycemic control in obese diabetic patients. To study its long-term metabolic effect, 40 obese patients with non-insulin -dependent diabetes mellitus (NIDDM) or impaired glucose tolera...

  18. Long-term effects of fluoxetine on glycemic control in obese patients with non-insulin-dependent diabetes mellitus or glucose intolerance

    DEFF Research Database (Denmark)

    Breum, Leif; Bjerre, U; Bak, J F

    1995-01-01

    Fluoxetine (F) is a specific serotonin-reuptake inhibitor that has been shown to promote weight loss and improve glycemic control in obese diabetic patients. To study its long-term metabolic effect, 40 obese patients with non-insulin -dependent diabetes mellitus (NIDDM) or impaired glucose...

  19. Preliminary application of a novel algorithm to monitor changes in pre-flight total peripheral resistance for prediction of post-flight orthostatic intolerance in astronauts

    Science.gov (United States)

    Arai, Tatsuya; Lee, Kichang; Stenger, Michael B.; Platts, Steven H.; Meck, Janice V.; Cohen, Richard J.

    2011-04-01

    Orthostatic intolerance (OI) is a significant challenge for astronauts after long-duration spaceflight. Depending on flight duration, 20-80% of astronauts suffer from post-flight OI, which is associated with reduced vascular resistance. This paper introduces a novel algorithm for continuously monitoring changes in total peripheral resistance (TPR) by processing the peripheral arterial blood pressure (ABP). To validate, we applied our novel mathematical algorithm to the pre-flight ABP data previously recorded from twelve astronauts ten days before launch. The TPR changes were calculated by our algorithm and compared with the TPR value estimated using cardiac output/heart rate before and after phenylephrine administration. The astronauts in the post-flight presyncopal group had lower pre-flight TPR changes (1.66 times) than those in the non-presyncopal group (2.15 times). The trend in TPR changes calculated with our algorithm agreed with the TPR trend calculated using measured cardiac output in the previous study. Further data collection and algorithm refinement are needed for pre-flight detection of OI and monitoring of continuous TPR by analysis of peripheral arterial blood pressure.

  20. Acceleration sensors in abdominal wall position as a non-invasive approach to detect early breathing alterations induced by intolerance of increased airway resistance.

    Science.gov (United States)

    Breuer, Thomas; Bruells, Christian S; Rossaint, Rolf; Steffen, Henning; Disselhorst-Klug, Catherine; Czaplik, Michael; Zoremba, Norbert

    2017-11-10

    Early detection of respiratory overload is crucial to mechanically ventilated patients, especially during phases of spontaneous breathing. Although a diversity of methods and indices has been established, there is no highly specific approach to predict respiratory failure. This study aimed to evaluate acceleration sensors in abdominal and thoracic wall positions to detect alterations in breathing excursions in a setting of gradual increasing airway resistance. Twenty-nine healthy volunteers were committed to a standardized protocol of a two-minutes step-down spontaneous breathing on a 5 mm, 4 mm and then 3 mm orally placed endotracheal tube. Accelerator sensors in thoracic and abdominal wall position monitored breathing excursions. 15 participants passed the breathing protocol ("completed" group), 14 individuals cancelled the protocol due to subjective intolerance to the increasing airway resistance ("abandoned" group). Gradual increased respiratory workload led to a significant decrease of acceleration in abdominal wall position in the "abandoned" group compared to the "completed" group (p breathing alterations prior to respiratory failure. EK 309-15; by the Ethics Committee of the Faculty of Medicine, RWTH Aachen, Aachen, Germany. Retrospectively registered 28th of December 2015.

  1. Rationale, design, and method of the Diabetes & Women's Health study – a study of long-term health implications of glucose intolerance in pregnancy and their determinants

    DEFF Research Database (Denmark)

    Zhang, Cuilin; Hu, Frank B; Olsen, Sjurdur F

    2014-01-01

    Women who develop gestational diabetes mellitus or impaired glucose tolerance during pregnancy are at substantially increased risk for type 2 diabetes and comorbidities after pregnancy. Little is known about the role of genetic factors and their interactions with environmental factors...... diabetes mellitus in two existing prospective cohorts, the Nurses' Health Study II and the Danish National Birth Cohort. Women who had a medical history of gestational diabetes mellitus in one or more of their pregnancies are eligible for the present study. After enrollment, we follow study participants...... for an additional 2 years to collect updated information on major clinical and environmental factors that may predict type 2 diabetes mellitus risk as well as with biospecimens to measure genetic and biochemical markers implicated in glucose metabolism. Newly collected data will be appended to the relevant existing...

  2. Phase 1 study of INNO-406, a dual Abl/Lyn kinase inhibitor, in Philadelphia chromosome-positive leukemias after imatinib resistance or intolerance.

    Science.gov (United States)

    Kantarjian, Hagop; le Coutre, Phillipp; Cortes, Jorge; Pinilla-Ibarz, Javier; Nagler, Arnon; Hochhaus, Andreas; Kimura, Shinya; Ottmann, Oliver

    2010-06-01

    : INNO-406, a dual v-abl Abelson murine leukemia viral oncogene homolog (Abl)/v-yes-1 Yamaguchi sarcoma viral-related oncogene homolog (Lyn) tyrosine kinase inhibitor (TKI), has demonstrated specific Lyn kinase inhibitory activity with no or limited activity against other sarcoma (Src) family member kinases. Several breakpoint cluster region (Bcr)-Abl kinase domain mutations are sensitive to INNO-406 in vitro, including mutations that involve a phenylalanine-to-leucine or phenylalanine-to-valine substitution at codon 317 (F317L and F317V, respectively). In the current study, the authors evaluated the use of INNO-406 in patients with Philadelphia (Ph) chromosome-positive chronic myelogenous leukemia (CML) or acute lymphocytic leukemia (ALL) after imatinib resistance or intolerance. : A dose-escalation study was conducted at a starting dose of oral INNO-406 30 mg once daily. Cohorts of at least 3 patients were treated at each dose level until the maximum tolerated dose (MTD) was reached. Twice-daily dosing also was evaluated. Therapy was allowed to continue for a maximum of 24 months. : INNO-406 was administered to 56 patients with imatinib resistance (n = 40) or intolerance (n = 16). Other previous treatments included nilotinib (n = 20 patients), dasatinib (n = 26 patients), and dasatinib/nilotinib (n = 9 patients). Common mutations at the time of study entry included a tyrosine-to-histidine substitution at codon 253 (Y253H) (n = 6 patients), a glycine-to-glutamic acid substitution at codon 250 (G250E) (n = 4 patients), a threonine-to-isoleucine substitution at codon 315 (T315I) (n = 4 patients), and F317L (n = 3 patients). Of 31 patients with CML in chronic phase who received INNO-406, the major cytogenetic response rate was 19%. No responses were observed in patients who had CML in accelerated phase, CML in blastic phase, or Ph-positive ALL. The dose-limiting toxicities (DLTs) at an INNO-406 dose of 480 mg twice daily were liver function abnormalities and

  3. Estudo da freqüência de diabetes mellitus e intolerância à glicose em pacientes com fibrose cística Study of the frequency of diabetes mellitus and glucose intolerance in patients with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Flávia A.A. de Castro

    2001-08-01

    Full Text Available OBJETIVO: avaliar a freqüência de diabetes mellitus (DM e de intolerância à glicose nos pacientes com fibrose cística seguidos no Serviço de Gastropediatria do HC-FMRP-USP. MÉTODOS: foi realizado estudo analítico transversal de um grupo de 25 pacientes mucoviscidóticos do HC-FMRP-USP. Foram realizados testes orais de tolerância à glicose (OGTT com determinação concomitante da glicemia e da insulinemia. Foram obtidas áreas sob as curvas da glicemia (G e da insulinemia (I e calculada a relação I/G, correlacionando-as com o tempo de doença clinicamente manifesta e função exócrina pancreática. RESULTADOS: cinco pacientes apresentaram alterações: um é diabético e quatro são intolerantes à glicose e/ou hiperinsulinêmicos. Há correlação direta entre a área sob a curva de insulinemia e o tempo de mucoviscidose. Verificou-se também relação inversa estatisticamente significativa entre a área sob a curva de insulinemia e o índice I/G com o número de cápsulas de enzima/kg/dia. CONCLUSÕES: a freqüência de alterações na homeostase glicêmica nos mucoviscidóticos estudados é maior que na população em geral (20% da amostra total e 33% do grupo de pacientes com glicemia e insulinemia no OGTT. Assim, é importante a realização sistemática de testes de tolerância à glicose em mucoviscidóticos, visando à detecção precoce de anormalidades metabólicas para adequado tratamento.ABSTRACT OBJECTIVE: To evaluate the frequency of diabetes mellitus and glucose intolerance in patients with cystic fibrosis treated at the Pediatric Gastroenterology Service of HC-FMRP-USP. METHODS: A cross-sectional analytical study was conducted on a group of 25 patients with mucoviscidosis who were followed up at HC-FMRP-USP. Oral glucose tolerance tests (OGTT were performed, with simultaneous determination of glycemia and insulinemia. Areas under the curve were obtained for glycemia (G and insulinemia (I and the I/G ratio was

  4. Low-Molecular-Weight Peptides from Salmon Protein Prevent Obesity-Linked Glucose Intolerance, Inflammation, and Dyslipidemia in LDLR-/-/ApoB100/100 Mice.

    Science.gov (United States)

    Chevrier, Geneviève; Mitchell, Patricia L; Rioux, Laurie-Eve; Hasan, Fida; Jin, Tianyi; Roblet, Cyril Roland; Doyen, Alain; Pilon, Geneviève; St-Pierre, Philippe; Lavigne, Charles; Bazinet, Laurent; Jacques, Hélène; Gill, Tom; McLeod, Roger S; Marette, André

    2015-07-01

    We previously reported that fish proteins can alleviate metabolic syndrome (MetS) in obese animals and human subjects. We tested whether a salmon peptide fraction (SPF) could improve MetS in mice and explored potential mechanisms of action. ApoB(100) only, LDL receptor knockout male mice (LDLR(-/-)/ApoB(100/100)) were fed a high-fat and -sucrose (HFS) diet (25 g/kg sucrose). Two groups were fed 10 g/kg casein hydrolysate (HFS), and 1 group was additionally fed 4.35 g/kg fish oil (FO; HFS+FO). Two other groups were fed 10 g SPF/kg (HFS+SPF), and 1 group was additionally fed 4.35 g FO/kg (HFS+SPF+FO). A fifth (reference) group was fed a standard feed pellet diet. We assessed the impact of dietary treatments on glucose tolerance, adipose tissue inflammation, lipid homeostasis, and hepatic insulin signaling. The effects of SPF on glucose uptake, hepatic glucose production, and inducible nitric oxide synthase activity were further studied in vitro with the use of L6 myocytes, FAO hepatocytes, and J774 macrophages. Mice fed HFS+SPF or HFS+SPF+FO diets had lower body weight (protein effect, P = 0.024), feed efficiency (protein effect, P = 0.018), and liver weight (protein effect, P = 0.003) as well as lower concentrations of adipose tissue cytokines and chemokines (protein effect, P ≤ 0.003) compared with HFS and HFS+FO groups. They also had greater glucose tolerance (protein effect, P < 0.001), lower activation of the mammalian target of rapamycin complex 1/S6 kinase 1/insulin receptor substrate 1 (mTORC1/S6K1/IRS1) pathway, and increased insulin signaling in liver compared with the HFS and HFS+FO groups. The HFS+FO, HFS+SPF, and HFS+SPF+FO groups had lower plasma triglycerides (protein effect, P = 0.003; lipid effect, P = 0.002) than did the HFS group. SPF increased glucose uptake and decreased HGP and iNOS activation in vitro. SPF reduces obesity-linked MetS features in LDLR(-/-)/ApoB(100/100) mice. The anti-inflammatory and glucoregulatory properties of SPF were

  5. Long-term safety and efficacy of dasatinib in the treatment of chronic-phase chronic myeloid leukemia patients resistant or intolerant to imatinib

    Directory of Open Access Journals (Sweden)

    Shoumariyeh K

    2014-09-01

    Full Text Available Khalid Shoumariyeh, Nikolas von BubnoffDepartment of Hematology, Oncology and Stem Cell Transplantation, University Hospital Freiburg, Freiburg, Germany Abstract: Treatment of chronic myeloid leukemia (CML has undergone dramatic changes in the last decade. Dissecting the molecular pathways that lead to the development of this disease resulted in the development of targeted therapy against the molecular driver of CML, namely the aberrantly activated tyrosine kinase BCR-ABL1. By introducing the tyrosine kinase inhibitor imatinib to the treatment repertoire, the natural course of the disease has been dramatically altered and overall survival of patients with CML prolonged substantially. Nevertheless, a significant number of patients are primarily resistant, acquire resistance during the course of their disease, or do not tolerate the intake of imatinib due to adverse effects. Second-generation tyrosine kinase inhibitors were developed in an attempt to overcome these problems. Dasatinib is a potent oral kinase inhibitor that was originally developed as an Src-kinase inhibitor but exhibited promising potency against BCR-ABL1 as well. Phase I and II trials demonstrated efficacy in patients failing imatinib, and thus dasatanib was approved in 2006 for the treatment of imatinib-resistant or -intolerant patients with chronic-phase CML harboring the BCR-ABL1 fusion protein. It has since shown promising efficacy and good overall tolerability in subsequent clinical trials, including the Phase III first-line DASISION trial that led to the extension of its approval for first-line treatment of chronic-phase CML. The following review summarizes the available data on the long-term efficacy and safety of dasatinib as a second-line therapy in chronic-phase CML. Keywords: BCR-ABL1, TKI, CML-CP, second-line treatment

  6. Pharmacokinetics of metformin in patients with gastrointestinal intolerance

    DEFF Research Database (Denmark)

    Mccreight, Laura J.; Stage, Tore B.; Connelly, Paul

    2018-01-01

    AIMS: Metformin intolerance symptoms are gastrointestinal in nature, but the underlying mechanism is poorly understood. The aim of this study was to assess potential causes of metformin intolerance including: altered metformin uptake from the intestine; increased anaerobic glucose utilisation...... and subsequent lactate production; altered serotonin uptake; and altered bile acid pool. METHODS: This pharmacokinetic study recruited ten severely intolerant and ten tolerant individuals matched for age, sex and BMI. A single 500mg dose of metformin was administered, with blood sampling at eleven time points...... over 24 hours. Blood samples were analysed for metformin, lactate, serotonin, and bile acid concentrations and compared across the phenotypes. RESULTS: The intolerant individuals were severely intolerant to 500mg metformin. No significant difference was identified between tolerant and intolerant...

  7. NN2211: a long-acting glucagon-like peptide-1 derivative with anti-diabetic effects in glucose-intolerant pigs

    DEFF Research Database (Denmark)

    Ribel, Ulla; Larsen, Marianne O; Rolin, Bidda

    2002-01-01

    Glucagon-like peptide-1 (GLP-1) is an effective anti-diabetic agent, but its metabolic instability makes it therapeutically unsuitable. This study investigated the pharmacodynamics of a long-acting GLP-1 derivative (NN2211: (Arg(34)Lys(26)-(N- epsilon -(gamma-Glu(N-alpha-hexadecanoyl)))-GLP-1...... a hyperglycaemic glucose clamp and chronic treatment results in better daily metabolic control. Therefore, NN2211, a GLP-1 derivative that can be administered once daily, holds promise as a new anti-diabetic drug with a minimal risk of hypoglycaemia....

  8. Insulin-resistant glucose metabolism in patients with microvascular angina--syndrome X

    DEFF Research Database (Denmark)

    Vestergaard, H; Skøtt, P; Steffensen, R

    1995-01-01

    insulin-stimulated glucose disposal to peripheral tissues was lower in patients with MA (13.4 +/- 1.0 v 18.2 +/- 1.4 mg.kg fat-free mass [FFM]-1.min-1, P metabolism (8.4 +/- 0.9 v 12.5 +/- 1.3 mg.kg FFM-1.min-1, P ...Studies in patients with microvascular angina (MA) or the cardiologic syndrome X have shown a hyperinsulinemic response to an oral glucose challenge, suggesting insulin resistance and a role for increased serum insulin in coronary microvascular dysfunction. The aim of the present study...... was to examine whether patients with MA are insulin-resistant. Nine patients with MA and seven control subjects were studied. All were sedentary and glucose-tolerant. Coronary arteriography was normal in all participants, and exercise-induced coronary ischemia was demonstrated in all MA patients. A euglycemic...

  9. Exogenous alanine and/or glucose plus kanamycin kills antibiotic-resistant bacteria.

    Science.gov (United States)

    Peng, Bo; Su, Yu-Bin; Li, Hui; Han, Yi; Guo, Chang; Tian, Yao-Mei; Peng, Xuan-Xian

    2015-02-03

    Multidrug-resistant bacteria are an increasingly serious threat to human and animal health. However, novel drugs that can manage infections by multidrug-resistant bacteria have proved elusive. Here we show that glucose and alanine abundances are greatly suppressed in kanamycin-resistant Edwardsiella tarda by GC-MS-based metabolomics. Exogenous alanine or glucose restores susceptibility of multidrug-resistant E. tarda to killing by kanamycin, demonstrating an approach to killing multidrug-resistant bacteria. The mechanism underlying this approach is that exogenous glucose or alanine promotes the TCA cycle by substrate activation, which in turn increases production of NADH and proton motive force and stimulates uptake of antibiotic. Similar results are obtained with other Gram-negative bacteria (Vibrio parahaemolyticus, Klebsiella pneumoniae, Pseudomonas aeruginosa) and Gram-positive bacterium (Staphylococcus aureus), and the results are also reproduced in a mouse model for urinary tract infection. This study establishes a functional metabolomics-based strategy to manage infection by antibiotic-resistant bacteria. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Insulin resistance for glucose metabolism in disused soleus muscle of mice

    Science.gov (United States)

    Seider, M. J.; Nicholson, W. F.; Booth, F. W.

    1981-01-01

    Results of this study on mice provide the first direct evidence of insulin resistance for glucose metabolism in skeletal muscle that has undergone a previous period of reduced muscle usage. This lack of responsiveness to insulin developed in one day and in the presence of hypoinsulinemia. Future studies will utilize the model of hindlimb immobilization to determine the causes of these changes.

  11. Dietary fructose intolerance, fructan intolerance and FODMAPs

    Science.gov (United States)

    Fedewa, Amy; Rao, Satish S. C.

    2014-01-01

    Dietary intolerances to fructose, fructans and FODMAPs (Fermentable Oligosaccharides, Disaccharides, Monosaccharides And Polyols) are common, yet poorly recognized and managed. Over the last decade, they have come to the forefront because of new knowledge on the mechanisms and treatment of these conditions. Patients with these problems often present with unexplained bloating, belching, distension, gas, abdominal pain or diarrhea. Here, we have examined the most up-to-date research on these food-related intolerances, discussed controversies, and have provided some guidelines for the dietary management of these conditions. Breath testing for carbohydrate intolerance appears to be standardized and essential for the diagnosis and management of these conditions, especially in the Western population. While current research shows that the FODMAP diet may be effective in treating irritable bowel syndrome, additional research is needed to identify more foods items that are high in FODMAPs, and to assess the long-term efficacy and safety of dietary interventions. PMID:24357350

  12. Dietary fructose intolerance, fructan intolerance and FODMAPs.

    Science.gov (United States)

    Fedewa, Amy; Rao, Satish S C

    2014-01-01

    Dietary intolerances to fructose, fructans and FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) are common, yet poorly recognized and managed. Over the last decade, they have come to the forefront because of new knowledge on the mechanisms and treatment of these conditions. Patients with these problems often present with unexplained bloating, belching, distension, gas, abdominal pain, or diarrhea. Here, we have examined the most up-to-date research on these food-related intolerances, discussed controversies, and have provided some guidelines for the dietary management of these conditions. Breath testing for carbohydrate intolerance appears to be standardized and essential for the diagnosis and management of these conditions, especially in the Western population. While current research shows that the FODMAP diet may be effective in treating some patients with irritable bowel syndrome, additional research is needed to identify more foods items that are high in FODMAPs, and to assess the long-term efficacy and safety of dietary interventions.

  13. Genetics Home Reference: lactose intolerance

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions Lactose intolerance Lactose intolerance Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Lactose intolerance is an impaired ability to digest lactose, ...

  14. Ateistiske begravelsespladser og intolerance

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2011-01-01

    Kronikken diskuterer Charlotte Dyremoses kritik af planerne om begravelsespladser fri for religiøse symboler for at være udtryk for intolerance.......Kronikken diskuterer Charlotte Dyremoses kritik af planerne om begravelsespladser fri for religiøse symboler for at være udtryk for intolerance....

  15. Religious intolerance and Euroscepticism

    NARCIS (Netherlands)

    Hobolt, S.B.; van der Brug, W.; de Vreese, C.H.; Boomgaarden, H.G.; Hinrichsen, M.C.

    2011-01-01

    Research on Euroscepticism focuses increasingly on the role of group identities: national identities and attitudes towards multiculturalism. Yet hardly any attention has been paid to the way in which religious intolerance shapes Euroscepticism. We argue that religious intolerance influences not only

  16. Effects of marine collagen peptides on glucose metabolism and insulin resistance in type 2 diabetic rats.

    Science.gov (United States)

    Zhu, CuiFeng; Zhang, Wei; Mu, Bo; Zhang, Fan; Lai, NanNan; Zhou, JianXin; Xu, AiMin; Liu, JianGuo; Li, Yong

    2017-07-01

    The present study was conducted to investigate the effects of marine collagen peptides (MCPs) on glucose metabolism and insulin resistance using a rat model of type 2 diabetes mellitus (T2DM). Forty T2DM obese Wistar rats were randomly assigned to receive varying doses of MCPs or a vehicle control for 4 weeks. Blood glucose and insulin levels, as well as oxidative stress and inflammation were measured. The expression of glucose transporter type 4 (GLUT4) in skeletal muscles and peroxisome proliferator-activated receptor-α (PPAR-α) in livers of T2DM rats was also measured. It was found that in the group of 9.0 g/kg/day MCPs significantly improved glucose, insulin, and homeostatic model assessment-insulin resistance, and increased the insulin sensitivity index (ISI). In addition, the groups of 4.5 and 2.25 g/kg/day MCPs significantly improved liver steatosis. It was also found that MCPs decreased expression of oxidative stress biomarkers and inflammatory cytokines and adipocytokines in T2DM rats. In conclusion, medium and high doses of MCPs (≥4.5 g/kg/day) improved glucose metabolism and insulin sensitivity in T2DM rats. These beneficial effects of MCPs may be mediated by decreasing oxidative stress and inflammation and by up-regulating GLUT4, and PPAR-α activity.

  17. Protein Kinase A Activation Promotes Cancer Cell Resistance to Glucose Starvation and Anoikis.

    Directory of Open Access Journals (Sweden)

    Roberta Palorini

    2016-03-01

    Full Text Available Cancer cells often rely on glycolysis to obtain energy and support anabolic growth. Several studies showed that glycolytic cells are susceptible to cell death when subjected to low glucose availability or to lack of glucose. However, some cancer cells, including glycolytic ones, can efficiently acquire higher tolerance to glucose depletion, leading to their survival and aggressiveness. Although increased resistance to glucose starvation has been shown to be a consequence of signaling pathways and compensatory metabolic routes activation, the full repertoire of the underlying molecular alterations remain elusive. Using omics and computational analyses, we found that cyclic adenosine monophosphate-Protein Kinase A (cAMP-PKA axis activation is fundamental for cancer cell resistance to glucose starvation and anoikis. Notably, here we show that such a PKA-dependent survival is mediated by parallel activation of autophagy and glutamine utilization that in concert concur to attenuate the endoplasmic reticulum (ER stress and to sustain cell anabolism. Indeed, the inhibition of PKA-mediated autophagy or glutamine metabolism increased the level of cell death, suggesting that the induction of autophagy and metabolic rewiring by PKA is important for cancer cellular survival under glucose starvation. Importantly, both processes actively participate to cancer cell survival mediated by suspension-activated PKA as well. In addition we identify also a PKA/Src mechanism capable to protect cancer cells from anoikis. Our results reveal for the first time the role of the versatile PKA in cancer cells survival under chronic glucose starvation and anoikis and may be a novel potential target for cancer treatment.

  18. Effect of mercury and organomercurials on cellular glucose utilization: a study using resting mercury-resistant yeast cells.

    Science.gov (United States)

    Ghosh, S K; Chaudhuri, J; Gachhui, R; Mandal, A; Ghosh, S

    2007-02-01

    Mercury compounds are highly toxic to all types of living cells. Isolated yeast strains of Rhodotorula rubra showed high and low resistance pattern towards mercury and organomercurial compounds. To investigate the basis of differential sensitivity of these two types of strains, glucose utilization was measured in the presence of mercury compounds. Glucose utilization process remained unaffected in resting cells of highly Hg(2+)-resistant strain in the presence of HgCl(2) but not in the presence of phenylmercuric acetate and thimerosal. However, HgCl(2) significantly affected glucose utilization in the case of low-resistant cells. The Hg-retaining ability of the cell wall of highly Hg(2+)-resistant yeast strain was greater than that of the weakly Hg(2+)-resistant strain. The spheroplast-bound Hg(2+) was also significantly less in the highly Hg(2+)-resistant strain than in the weakly Hg(2+)-resistant strain. Glucose uptake machinery was not affected in the presence of toxic metal ions in the case of high-resistant strains. But in the case of low Hg(2+)-resistant strain, glucose transport system may be affected either by inactivation of sensor proteins containing -SH group associated with glucose uptake. Cell wall of mercury-resistant yeast cells may play an important role in heavy metal bioremediation process.

  19. Humanin skeletal muscle protein levels increase after resistance training in men with impaired glucose metabolism.

    Science.gov (United States)

    Gidlund, Eva-Karin; von Walden, Ferdinand; Venojärvi, Mika; Risérus, Ulf; Heinonen, Olli J; Norrbom, Jessica; Sundberg, Carl Johan

    2016-12-01

    Humanin (HN) is a mitochondrially encoded and secreted peptide linked to glucose metabolism and tissue protecting mechanisms. Whether skeletal muscle HN gene or protein expression is influenced by exercise remains unknown. In this intervention study we show, for the first time, that HN protein levels increase in human skeletal muscle following 12 weeks of resistance training in persons with prediabetes. Male subjects (n = 55) with impaired glucose regulation (IGR) were recruited and randomly assigned to resistance training, Nordic walking or a control group. The exercise interventions were performed three times per week for 12 weeks with progressively increased intensity during the intervention period. Biopsies from the vastus lateralis muscle and venous blood samples were taken before and after the intervention. Skeletal muscle and serum protein levels of HN were analyzed as well as skeletal muscle gene expression of the mitochondrially encoded gene MT-RNR2, containing the open reading frame for HN To elucidate mitochondrial training adaptation, mtDNA, and nuclear DNA as well as Citrate synthase were measured. Skeletal muscle HN protein levels increased by 35% after 12 weeks of resistance training. No change in humanin protein levels was seen in serum in any of the intervention groups. There was a significant correlation between humanin levels in serum and the improvements in the 2 h glucose loading test in the resistance training group. The increase in HN protein levels in skeletal muscle after regular resistance training in prediabetic males may suggest a role for HN in the regulation of glucose metabolism. Given the preventative effect of exercise on diabetes type 2, the role of HN as a mitochondrially derived peptide and an exercise-responsive mitokine warrants further investigation. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  20. Resistance training enhances insulin suppression of endogenous glucose production in elderly women.

    Science.gov (United States)

    Honka, Miikka-Juhani; Bucci, Marco; Andersson, Jonathan; Huovinen, Ville; Guzzardi, Maria Angela; Sandboge, Samuel; Savisto, Nina; Salonen, Minna K; Badeau, Robert M; Parkkola, Riitta; Kullberg, Joel; Iozzo, Patricia; Eriksson, Johan G; Nuutila, Pirjo

    2016-03-15

    An altered prenatal environment during maternal obesity predisposes offspring to insulin resistance, obesity, and their consequent comorbidities, type 2 diabetes and cardiovascular disease. Telomere shortening and frailty are additional risk factors for these conditions. The aim of this study was to evaluate the effects of resistance training on hepatic metabolism and ectopic fat accumulation. Thirty-five frail elderly women, whose mothers' body mass index (BMI) was known, participated in a 4-mo resistance training program. Endogenous glucose production (EGP) and hepatic and visceral fat glucose uptake were measured during euglycemic hyperinsulinemia with [(18)F]fluorodeoxyglucose and positron emission tomography. Ectopic fat was measured using magnetic resonance spectroscopy and imaging. We found that the training intervention reduced EGP during insulin stimulation [from 5.4 (interquartile range 3.0, 7.0) to 3.9 (-0.4, 6.1) μmol·kg body wt(-1)·min(-1), P = 0.042] in the whole study group. Importantly, the reduction was higher among those whose EGP was more insulin resistant at baseline (higher than the median) [-5.6 (7.1) vs. 0.1 (5.4) μmol·kg body wt(-1)·min(-1), P = 0.015]. Furthermore, the decrease in EGP was associated with telomere elongation (r = -0.620, P = 0.001). The resistance training intervention did not change either hepatic or visceral fat glucose uptake or the amounts of ectopic fat. Maternal obesity did not influence the studied measures. In conclusion, resistance training improves suppression of EGP in elderly women. The finding of improved insulin sensitivity of EGP with associated telomere lengthening implies that elderly women can reduce their risk for type 2 diabetes and cardiovascular disease with resistance training. Copyright © 2016 the American Physiological Society.

  1. The molecular basis of lactose intolerance.

    Science.gov (United States)

    Campbell, Anthony K; Waud, Jonathan P; Matthews, Stephanie B

    2009-01-01

    A staggering 4000 million people cannot digest lactose, the sugar in milk, properly. All mammals, apart from white Northern Europeans and few tribes in Africa and Asia, lose most of their lactase, the enzyme that cleaves lactose into galactose and glucose, after weaning. Lactose intolerance causes gut and a range of systemic symptoms, though the threshold to lactose varies considerably between ethnic groups and individuals within a group. The molecular basis of inherited hypolactasia has yet to be identified, though two polymorphisms in the introns of a helicase upstream from the lactase gene correlate closely with hypolactasia, and thus lactose intolerance. The symptoms of lactose intolerance are caused by gases and toxins produced by anaerobic bacteria in the large intestine. Bacterial toxins may play a key role in several other diseases, such as diabetes, rheumatoid arthritis, multiple sclerosis and some cancers. The problem of lactose intolerance has been exacerbated because of the addition of products containing lactose to various foods and drinks without being on the label. Lactose intolerance fits exactly the illness that Charles Darwin suffered from for over 40 years, and yet was never diagnosed. Darwin missed something else--the key to our own evolution--the Rubicon some 300 million years ago that produced lactose and lactase in sufficient amounts to be susceptible to natural selection.

  2. Blood glucose lowering effect of ophiopogonis tuber extract and mechanism of anti-insulin-resistance

    Directory of Open Access Journals (Sweden)

    Meng NING

    2013-01-01

    Full Text Available Objective  To study the hypoglycemic effect and insulin sensitization mechanism of ophiopogonis tuber extracts on the 3T3-L1-induced adipocytes, and also in rats with reproduction of type 2 diabetes mellitus (T2DM. Methods  3T3-L1 cells were induced and differentiated into adipocytes. After the intervention with ophiopogonpolysaccharide (OPSR and ophiopogonin (OPG, glucose consuming rate was detected for screening the extracts which may have effective hypoglycemic effects. The insulin resistance (IR adipocyte model was established by dexamethasone induction, and then it was treated with OPSR. The protein expression levels of leptin, adiponectin and resistin were detected by Western blotting. The T2DM rat model was reproduced and then treated with OPSR for 4 weeks. Body weight (BW, triglyeride (TG, fasting blood glucose (FBG and fasting insulin (FINs of the rats were measured respectively. Results  OPSR in dosage of 0.5-50mg/L promoted glucose consumption of adipocytes in a dose-dependent manner, the glucose consumption ratios were 32.27%, 75.14% and 90.47% respectively. OPG of 50mg/L showed very weak activity with glucose consumption ratio of only 8.49%. OPSR could significantly promote the protein expression of leptin and adiponectin, and showed an inhibitory effect on the protein expression of resistin (P<0.05. After treatment with OPSR for 4 weeks, the BW of rats increased obviously, while TG, FBG and HOMA-IR decreased significantly (P<0.05 or P<0.01. Conclusions  OPSR may promote glucose transport and utilization of adipocytes, decrease the level of FBG and TG, and improve the condition of IR in T2DM rats. The mechanism of blood glucose lowering effect may be attributed to secretion of adipokines, such as leptin, adiponectin and resistin by IR adipocytes.

  3. Lactose Intolerance and Symptom Pattern of Lactose Intolerance among Healthy Volunteers.

    Science.gov (United States)

    Saha, Madhusudan; Parveen, Irin; Shil, Bimal Chandra; Saha, Shasanka Kumar; Banik, Ranjit Kumar; Majumder, Monojit; Salam, Mahjuba Umme; Islam, Asm Nazmul

    2016-01-01

    To see the prevalence of lactose intolerance (LI) and related symptoms following oral lactose challenge in healthy volunteers. Symptoms of abdominal pain, nausea, borborygmi, flatulence, and diarrhea were noted for 24 hours and blood glucose was estimated at 0 hour and 30 minutes after 25 gm oral lactose load to healthy volunteers. Failure to rise blood glucose level ≥ 1.1 mmol/l at 30 minutes after lactose intake from fasting level was taken as lactose malabsorption (LM), i.e., LI. A total of 166 volunteers (123 males, 43 females) with a mean age 34.78 ± 11.45 years participated in this study. Lactose intolerance was found among 85.54% (n = 142, M = 104, F = 38). The main symptoms of LI were diarrhea (n = 83, 58.4.0%), borborygmi (n = 81, 57.04%), abdominal pain (n = 35, 24.65%), and flatulence (n = 27, 19.0%). Lactose intolerance among healthy adults may be common in Bangladesh. Diarrhea and borborygmi were mostly associated symptoms of LI. Saha M, Parveen I, Shil BC, Saha SK, Banik RK, Majumder M, Salam MU, Nazmul Islam ASM. Lactose Intolerance and Symptom Pattern of Lactose Intolerance among Healthy Volunteers. Euroasian J Hepato-Gastroenterol 2016;6(1):5-7.

  4. Lactose Intolerance (For Kids)

    Science.gov (United States)

    ... groups of people — about 90% or more of Asian Americans and Native Americans are lactose intolerant, and ... aged cheeses, including cheddar. Yogurt that contains live cultures is more easily digested because it contains healthy ...

  5. Lactose Intolerance (For Teens)

    Science.gov (United States)

    ... intolerant for different reasons: Ethnic background. People of Asian, African, Native American, and Hispanic backgrounds are more ... are lower in lactose. Yogurts that contain active cultures are easier to digest and much less likely ...

  6. Glucose-to-insulin ratio rather than sex hormone-binding globulin and adiponectin levels is the best predictor of insulin resistance in nonobese women with polycystic ovary syndrome.

    Science.gov (United States)

    Ducluzeau, Pierre-Henri; Cousin, Patrice; Malvoisin, Etienne; Bornet, Hubert; Vidal, Hubert; Laville, Martine; Pugeat, Michel

    2003-08-01

    Polycystic ovary syndrome (PCOS), the main androgen disorder in women, has been suggested to be associated with a high risk of developing cardiovascular disease and type 2 diabetes. In many PCOS patients, overweight or central obesity is generally associated with increases in fasting insulin levels, insulin resistance, and glucose intolerance, and has been identified as a target for new therapeutic strategy, including early change in lifestyle. Early biochemical marker(s) for identifying at-risk patients will be useful for prevention studies. The main goal of the present study was to search for such tool(s). We investigated 16 nonobese PCOS women by performing euglycemic hyperinsulinemic clamp and measuring insulin levels during fasting and oral glucose tolerance test, as well as the serum concentrations of SHBG, leptin, and adiponectin, the newly identified adipose factors. Eight of the 16 patients had a steady-state glucose disposal rate less than 8.5 mg/kg.min, the lowest normal value for nonobese control women. These insulin-resistant patients had significant higher body mass index (BMI) and waist-to-hip ratio (WHR), and lower high-density lipoprotein cholesterol and SHBG levels. As expected, glucose disposal correlated negatively with BMI (P = 0.01), WHR (P = 0.01), and fasting insulin level (P = 0.003). On stepwise regression analysis, however, the glucose-to-insulin ratio (GIR) emerged as the strongest independent parameter to appraise insulin resistance (R(2) = 0.61). SHBG level correlated positively with GIR (P < 0.001) and negatively with BMI (P = 0.003) but did not correlate with either insulin response during the glucose tolerance test or plasma leptin and/or adiponectin levels. In contrast, BMI was the only independent predictive parameter of SHBG (P = 0.003, R(2) = 0.73). Interestingly, plasma adiponectin levels were positively associated with glucose disposal rate (P = 0.043) and negatively with WHR (P = 0.024), waist circumference being the best

  7. Skeletal Muscle TRIB3 Mediates Glucose Toxicity in Diabetes and High- Fat Diet–Induced Insulin Resistance

    Science.gov (United States)

    Wu, Mengrui; Kim, Teayoun; Jariwala, Ravi H.; Garvey, W. John; Luo, Nanlan; Kang, Minsung; Ma, Elizabeth; Tian, Ling; Steverson, Dennis; Yang, Qinglin; Fu, Yuchang

    2016-01-01

    In the current study, we used muscle-specific TRIB3 overexpressing (MOE) and knockout (MKO) mice to determine whether TRIB3 mediates glucose-induced insulin resistance in diabetes and whether alterations in TRIB3 expression as a function of nutrient availability have a regulatory role in metabolism. In streptozotocin diabetic mice, TRIB3 MOE exacerbated, whereas MKO prevented, glucose-induced insulin resistance and impaired glucose oxidation and defects in insulin signal transduction compared with wild-type (WT) mice, indicating that glucose-induced insulin resistance was dependent on TRIB3. In response to a high-fat diet, TRIB3 MOE mice exhibited greater weight gain and worse insulin resistance in vivo compared with WT mice, coupled with decreased AKT phosphorylation, increased inflammation and oxidative stress, and upregulation of lipid metabolic genes coupled with downregulation of glucose metabolic genes in skeletal muscle. These effects were prevented in the TRIB3 MKO mice relative to WT mice. In conclusion, TRIB3 has a pathophysiological role in diabetes and a physiological role in metabolism. Glucose-induced insulin resistance and insulin resistance due to diet-induced obesity both depend on muscle TRIB3. Under physiological conditions, muscle TRIB3 also influences energy expenditure and substrate metabolism, indicating that the decrease and increase in muscle TRIB3 under fasting and nutrient excess, respectively, are critical for metabolic homeostasis. PMID:27207527

  8. Biological Effects of Potato Plants Transformation with Glucose Oxidase Gene and their Resistance to Hyperthermia

    Directory of Open Access Journals (Sweden)

    O.I. Grabelnych

    2017-02-01

    Full Text Available It is known that regulation of plant tolerance to adverse environmental factors is connected with short term increase of the concentration of endogenous reactive oxygen species (ROS, which are signalling molecules for the induction of protective mechanisms. Introduction and expression of heterologous gox gene, which encodes glucose oxidase enzyme in plant genome, induce constantly higher content of hydrogen peroxide in plant tissues. It is not known how the introduction of native or modified gox gene affects the plant resistance to high-temperature stress, one of the most commonly used model for the study of stress response and thermal tolerance. In this study, we investigated biological effects of transformation and evaluated the resistance to temperature stress of potato plants with altered levels of glucose oxidase expression. Transformation of potato plants by gox gene led to the more early coming out from tuber dormancy of transformed plants and slower growth rate. Transformants containing the glucose oxidase gene were more sensitive to lethal thermal shock (50 °C, 90 min than the transformant with the empty vector (pBI or untransformed plants (CK. Pre-heating of plants at 37 °C significantly weakened the damaging effect of lethal thermal shock. This attenuation was more significant in the non-transformed plants.

  9. Glucose intolerance in the West African Diaspora

    DEFF Research Database (Denmark)

    Nielsen, Jannie; Christensen, Dirk Lund

    2011-01-01

    In the United States, Black Americans are largely descendants of West African slaves; they have a higher relative proportion of obesity and experience a higher prevalence of diabetes than White Americans. However, obesity rates alone cannot explain the higher prevalence of type 2 diabetes. Type 2...

  10. Efeito do tratamento com etanol sobre a gliconeogênese em ratos intolerantes à glicose - DOI: 10.4025/actascihealthsci.v31i2.4653 Effect of ethanol treatment on gluconeogenesis in glucose-intolerant rats- DOI: 10.4025/actascihealthsci.v31i2.4653

    Directory of Open Access Journals (Sweden)

    Francisco Pereira Silva

    2009-09-01

    Full Text Available O objetivo deste trabalho foi avaliar a influência do tratamento com etanol (Et sobre a gliconeogênese em ratos intolerantes à glicose. A intolerância à glicose foi induzida pela injeção de dexametasona (DEXA (0,1 mg kg-1; s.c., quatro dias. O teste de tolerância à glicose (GTT e os experimentos de perfusão de fígado in situ (avaliação da gliconeogênese foram realizados em ratos submetidos a jejum de 15h dos grupos experimentais: Controle (salina 0,9%, s.c., quatro dias; DEX (DEXA 0,1 mg kg-1; s.c., quatro dias; DEX+Et 3% (per os, 14 dias; DEX+Et 20% (per os, 14 dias; DEX+Met (Mettformina 300 mg kg-1, per os, quatro dias. Os animais tratados com DEX apresentaram elevada concentração de glicose sanguínea e também no perfusato coletado. O tratamento com metformina promoveu redução significativa na concentração de glicose no perfusato obtido de animais intolerantes à glicose. Entretanto, somente o tratamento com Et 3% promoveu redução na intolerância à glicose, mas não na produção da glicose hepática observada em animais DEX. Os dados obtidos demonstram que a administração de Et 3% melhora a intolerância à glicose induzida pela DEX sem influenciar na gliconeogênese, diferentemente do observado pelo tratamento com a metformina.In this work, the influence of ethanol (Et treatment on gluconeogenesis in glucose-intolerance rats was evaluated. Glucose intolerance in rats was induced by dexamethasone (DEXA injection (0.1 mg kg-1; s.c., 4 days. The glucose tolerance test (GTT and liver perfusion in situ experiments (gluconeogenesis evaluation were performed with 15-hour fasted rats in the following experimental groups: Control (saline 0.9%, s.c., 4 days; DEX (DEXA 0.1 mg kg-1; s.c., 4 days; DEX+Et 3% (per os, 14 days; DEX+Et 20% (per os, 14 days; DEX+Met (Metformin 300 mg kg-1, per os, 4 days. DEX-treated animals showed high glucose concentration in blood and also in the perfusate collected. Metformin treatment resulted

  11. Correcting Postprandial Hyperglycemia in Zucker Diabetic Fatty Rats With an SGLT2 Inhibitor Restores Glucose Effectiveness in the Liver and Reduces Insulin Resistance in Skeletal Muscle.

    Science.gov (United States)

    O'Brien, Tracy P; Jenkins, Erin C; Estes, Shanea K; Castaneda, Antonio V; Ueta, Kiichiro; Farmer, Tiffany D; Puglisi, Allison E; Swift, Larry L; Printz, Richard L; Shiota, Masakazu

    2017-05-01

    Ten-week-old Zucker diabetic fatty (ZDF) rats at an early stage of diabetes embody metabolic characteristics of obese human patients with type 2 diabetes, such as severe insulin and glucose intolerance in muscle and the liver, excessive postprandial excursion of plasma glucose and insulin, and a loss of metabolic flexibility with decreased lipid oxidation. Metabolic flexibility and glucose flux were examined in ZDF rats during fasting and near-normal postprandial insulinemia and glycemia after correcting excessive postprandial hyperglycemia using treatment with a sodium-glucose cotransporter 2 inhibitor (SGLT2-I) for 7 days. Preprandial lipid oxidation was normalized, and with fasting, endogenous glucose production (EGP) increased by 30% and endogenous glucose disposal (E-Rd) decreased by 40%. During a postprandial hyperglycemic-hyperinsulinemic clamp after SGLT2-I treatment, E-Rd increased by normalizing glucose effectiveness to suppress EGP and stimulate hepatic glucose uptake; activation of glucokinase was restored and insulin action was improved, stimulating muscle glucose uptake in association with decreased intracellular triglyceride content. In conclusion, SGLT2-I treatment improves impaired glucose effectiveness in the liver and insulin sensitivity in muscle by eliminating glucotoxicity, which reinstates metabolic flexibility with restored preprandial lipid oxidation and postprandial glucose flux in ZDF rats. © 2017 by the American Diabetes Association.

  12. Assessment of insulin resistance in fructose-fed rats with 125I-6-deoxy-6-iodo-D-glucose, a new tracer of glucose transport

    International Nuclear Information System (INIS)

    Perret, Pascale; Slimani, Lotfi; Briat, Arnaud; Villemain, Daniele; Fagret, Daniel; Ghezzi, Catherine; Halimi, Serge; Demongeot, Jacques

    2007-01-01

    Insulin resistance, characterised by an insulin-stimulated glucose transport defect, is an important feature of the pre-diabetic state that has been observed in numerous pathological disorders. The purpose of this study was to assess variations in glucose transport in rats using 125 I-6-deoxy-6-iodo-D-glucose (6DIG), a new tracer of glucose transport proposed as an imaging tool to assess insulin resistance in vivo. Two protocols were performed, a hyperinsulinaemic-euglycaemic clamp and a normoinsulinaemic-normoglycaemic protocol, in awake control and insulin-resistant fructose-fed rats. The tracer was injected at steady state, and activity in 11 tissues and the blood was assessed ex vivo at several time points. A multicompartmental mathematical model was developed to obtain fractional transfer coefficients of 6DIG from the blood to the organs. Insulin sensitivity of fructose-fed rats, estimated by the glucose infusion rate, was reduced by 40% compared with control rats. At steady state, 6DIG uptake was significantly stimulated by insulin in insulin-sensitive tissues of control rats (basal versus insulin: diaphragm, p < 0.01; muscle, p < 0.05; heart, p < 0.001), whereas insulin did not stimulate 6DIG uptake in insulin-resistant fructose-fed rats. Moreover, in these tissues, the fractional transfer coefficients of entrance were significantly increased with insulin in control rats (basal vs insulin: diaphragm, p < 0.001; muscle, p < 0.001; heart, p < 0.01) whereas no significant changes were observed in fructose-fed rats. This study sets the stage for the future use of 6DIG as a non-invasive means for the evaluation of insulin resistance by nuclear imaging. (orig.)

  13. The effect of insulin resistance on amygdale glucose metabolism alterations in experimental Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Ya. V. Gorina

    2017-01-01

    Full Text Available Purpose. Glucose metabolism is tightly regulated in the brain. Aberrant glucose metabolism is an important feature of neurodegenerative diseases, as inAlzheimer’s disease. The transport of glucose to the cell membrane is realized through the activity of insulin-regulated aminopeptidase (IRAP which controls transfer of glucose transporter to the plasma membrane. IRAP is considered as one of the key markers of insulin resistance in Alzheimer’s disease. However, the question of the mechanism of the action of the IRAP remains open. The aim of the study was to study the effect of IRAP expression on cells of the neuronal and glial lineage, glucose transporter (GLUT4 expression in the brain amygdala on emotional memory in animals with experimental Alzheimer’s disease.Materials and methods. The study was performed with two experimental models of Alzheimer’s disease in mice. The experimental group was mice of the CD1 line, males aged 4 months (Alzheimer’s disease model with the intra-hippocampal administration of beta-amyloid 1-42 (1 µl bilaterally in the CA1 area. The control group was mice of the CD1 line, males aged 4 months (sham-operated animals with the intrahippocampal administration of Phosphate buffered salin (1 µl bilaterally in the CA1. The genetic model of Alzheimer’s disease is the B6SLJ-Tg line mice (APPSwFlLon, PSEN1*M146L*L286V 6799Vas, males aged 4 months. The control group consisted of C57BL/6xSJL mice, males aged 4 months. Evaluation of emotional memory was carried out using “Fear conditioning” protocol. Expression of molecule-markers of insulin-resistance in the amygdala was studied by immunohistochemistry followed by confocal microscopy.Results. Aberrant associative learning and emotional memory was revealed in animals with an experimental model of Alzheimer’s disease. A decrease (p ≤ 0,05 of IRAP expression on cells of neuronal and glial nature, associated with GLUT4 down-regulation was detected in amygdala of

  14. Continuous Glucose Monitoring in Patients with Abnormal Glucose Tolerance during Pregnancy: A Case Series

    Directory of Open Access Journals (Sweden)

    Mie Tonoike

    2016-01-01

    Full Text Available Abnormal glucose tolerance during pregnancy is associated with perinatal complications. We used continuous glucose monitoring (CGM in pregnant women with glucose intolerance to achieve better glycemic control and to evaluate the maternal glucose fluctuations. We also used CGM in women without glucose intolerance (the control cases. Furthermore, the standard deviation (SD and mean amplitude of glycemic excursions (MAGE were calculated for each case. For the control cases, the glucose levels were tightly controlled within a very narrow range; however, the SD and MAGE values in pregnant women with glucose intolerance were relativity high, suggesting postprandial hyperglycemia. Our results demonstrate that pregnant women with glucose intolerance exhibited greater glucose fluctuations compared with the control cases. The use of CGM may help to improve our understanding of glycemic patterns and may have beneficial effects on perinatal glycemic control, such as the detection of postprandial hyperglycemia in pregnant women.

  15. Carbapenem-Resistant Non-Glucose-Fermenting Gram-Negative Bacilli: the Missing Piece to the Puzzle

    Science.gov (United States)

    Gniadek, Thomas J.; Carroll, Karen C.

    2016-01-01

    The non-glucose-fermenting Gram-negative bacilli Pseudomonas aeruginosa and Acinetobacter baumannii are increasingly acquiring carbapenem resistance. Given their intrinsic antibiotic resistance, this can cause extremely difficult-to-treat infections. Additionally, resistance gene transfer can occur between Gram-negative species, regardless of their ability to ferment glucose. Thus, the acquisition of carbapenemase genes by these organisms increases the risk of carbapenemase spread in general. Ultimately, infection control practitioners and clinical microbiologists need to work together to determine the risk carried by carbapenem-resistant non-glucose-fermenting Gram-negative bacilli (CR-NF) in their institution and what methods should be considered for surveillance and detection of CR-NF. PMID:26912753

  16. Astaxanthin prevents loss of insulin signaling and improves glucose metabolism in liver of insulin resistant mice.

    Science.gov (United States)

    Bhuvaneswari, Saravanan; Anuradha, Carani Venkatraman

    2012-11-01

    This study investigates the effects of astaxanthin (ASX) on insulin signaling and glucose metabolism in the liver of mice fed a high fat and high fructose diet (HFFD). Adult male Mus musculus mice of body mass 25-30 g were fed either normal chow or the HFFD. After 15 days, mice in each group were subdivided among 2 smaller groups and treated with ASX (2 mg·(kg body mass)⁻¹) in olive oil for 45 days. At the end of 60 days, HFFD-fed mice displayed insulin resistance while ASX-treated HFFD animals showed marked improvement in insulin sensitivity parameters. ASX treatment normalized the activities of hexokinase, pyruvate kinase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glycogen phosphorylase, and increased glycogen reserves in the liver. Liver tissue from ASX-treated HFFD-fed animals showed increased tyrosine phosphorylation and decreased serine phosphorylation of insulin receptor substrates (IRS)-1 and -2. ASX increased IRS 1/2 and phosphatidylinositol 3-kinase (PI3K) association and serine phosphorylation of Akt. In addition, ASX decreased HFFD-induced serine kinases (c-jun N-terminal kinase-1 and extracellular signal-regulated kinase-1). The results suggest that ASX treatment promotes the IRS-PI3K-Akt pathway of insulin signaling by decreasing serine phosphorylation of IRS proteins, and improves glucose metabolism by modulating metabolic enzymes.

  17. Comparable Effects of Brief Resistance Exercise and Isotime Sprint Interval Exercise on Glucose Homeostasis in Men

    Directory of Open Access Journals (Sweden)

    Tomas K. Tong

    2017-01-01

    Full Text Available This study compared the effects of a single bout of resistance exercise (RES on glycemic homeostasis to isotime sprint interval exercise (SIE using a within-subjects design. Nineteen nondiabetic males (age: 23.3±0.7 yrs; height: 173.1±1.2 cm; weight: 79.1±4.8 kg; % fat: 22.5±2.5% were studied. RES involved nine exercises of 10 repetitions at 75% 1-RM using a 2 : 2 s tempo and was interspersed with a one-minute recovery; SIE involved four 30 s’ all-out cycling effort interspersed with four minutes of active recovery. Plasma glucose and insulin in response to a 75 g oral glucose tolerance test were assessed 12 h after exercise. In comparison to a no exercise control trial (CON, the area under curve (AUC of plasma glucose was reduced with both RES and SIE (P0.05. Such findings suggest that the RES may represent a potential alternative to the SIE in the development of time-efficient lifestyle intervention strategies for improving diabetes risk factors in healthy populations.

  18. Assessment of insulin resistance in Chinese PCOS patients with normal glucose tolerance.

    Science.gov (United States)

    Gao, Jing; Zhou, Li; Hong, Jie; Chen, Chen

    2017-11-01

    The study aimed to investigate insulin resistance (IR) status in polycystic ovary syndrome (PCOS) women with normal glucose tolerance (NGT), and further to evaluate feasible diagnostic method for those patients. Three hundred and twenty-five PCOS women with NGT and ninety-five healthy age-matched controls were recruited with Rotterdam criterion and 75 g oral glucose tolerance test (OGTT). IR status was estimated following a glycemic and insulinemic OGTT (0, 30, 60, 120, and 180 min). A modified HOMA-IR formula was applied to each time-course value of glycemia and insulinemia. The predictive performance of each IR index was analyzed with the use of ROC curves. Compared with healthy controls, both non-obese and obese PCOS patients with NGT had a higher BMI, serum glucose, insulin value (p PCOS-NGT was a HOMA-M30 value of 20.36 or more (AUC: 0.753). In obese PCOS-NGT population, the best predictive performance was obtained by a HOMA-M60 value of 32.17 or more (AUC: 0.868). IR was common in Chinese PCOS women with NGT, and the early assessment of IR should be heeded. We recommended HOMA-M30 (Cutoff: 20.36) and HOMA-M60 (Cutoff: 32.17) as the best predictive parameters for non-obese and obese PCOS-NGT patients, respectively.

  19. Sexual dimorphism in the glucose homeostasis phenotype of the Aromatase Knockout (ArKO) mice.

    Science.gov (United States)

    Van Sinderen, Michelle; Steinberg, Gregory; Jorgensen, Sebastian B; Honeyman, Jane; Chow, Jenny D Y; Simpson, Evan R; Jones, Margaret E E; Boon, Wah Chin

    2017-06-01

    We investigated the effects of estrogens on glucose homeostasis using the Aromatase Knockout (ArKO) mouse, which is unable to convert androgens into estrogens. The ArKO mouse is a model of total estrogen ablation which develops symptoms of metabolic syndrome. To determine the development and progression of whole body state of insulin resistance of ArKO mice, comprehensive whole body tolerance tests were performed on WT, ArKO and estrogen administrated mice at 3 and 12 months of age. The absence of estrogens in the male ArKO mice leads to hepatic insulin resistance, glucose and pyruvate intolerance from 3 to 12 months with consistent improvement upon estrogen treatment. Estrogen absence in the female ArKO mice leads to glucose intolerance without pyruvate intolerance or insulin resistance. The replacement of estrogens in the female WT and ArKO mice exhibited both insulin sensitizing and resistance effects depending on age and dosage. In conclusion, this study presents information on the sexually dimorphic roles of estrogens on glucose homeostasis regulation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Wheat and gluten intolerance

    NARCIS (Netherlands)

    Busink-van den Broeck, Hetty; Gilissen, L.J.W.J.; Brouns, F.

    2016-01-01

    With this White Paper, the current state of scientific knowledge on human disorders related to gluten and wheat is presented, with reference to other grains such as spelt, barley, rye, and oats. Backgrounds are described of coeliac disease (gluten intolerance), wheat allergies and any kind of wheat

  1. Management of statin intolerance

    Directory of Open Access Journals (Sweden)

    Soma B Raju

    2013-01-01

    Full Text Available Statins are the revolutionary drugs in the cardiovascular pharmacotherapy. But they also possess several adverse effects like myopathy with elevation of hepatic transaminases (>3 times the upper limit of normal or creatine kinase (>10 times the upper limit of normal and some rare side-effects, including peripheral neuropathy, memory loss, sleep disturbances, and erectile dysfunction. Due to these adverse effects, patients abruptly withdrew statins without consulting physicians. This abrupt discontinuation of statins is termed as statin intolerance. Statin-induced myopathy constitutes two third of all side-effects from statins and is the primary reason for statin intolerance. Though statin intolerance has considerably impacted cardiovascular outcomes in the high-risk patients, it has been well effectively managed by prescribing statins either as alternate-day or once weekly dosage regimen, as combination therapy with a non-statin therapy or and by dietary intervention. The present article reviews the causes, clinical implications of statin withdrawal and management of statin intolerance.

  2. Evolution and Collective Intolerance

    Science.gov (United States)

    Willhoite, Fred H., Jr.

    1977-01-01

    Examines behavioral and intellectual conformity as major attitudes in shaping political behavior. Manifestations of coercion within human and animal social units are presented, including religious intolerance, prohibition of artistic activity and literary expression, and rejection of outsiders. Available from: Managing Editor, Department of…

  3. 2-deoxy-D-glucose-induced metabolic stress enhances resistance to Listeria monocytogenes infection in mice

    Science.gov (United States)

    Miller, E. S.; Bates, R. A.; Koebel, D. A.; Fuchs, B. B.; Sonnenfeld, G.

    1998-01-01

    Exposure to different forms of psychological and physiological stress can elicit a host stress response, which alters normal parameters of neuroendocrine homeostasis. The present study evaluated the influence of the metabolic stressor 2-deoxy-D-glucose (2-DG; a glucose analog, which when administered to rodents, induces acute periods of metabolic stress) on the capacity of mice to resist infection with the facultative intracellular bacterial pathogen Listeria monocytogenes. Female BDF1 mice were injected with 2-DG (500 mg/kg b. wt.) once every 48 h prior to, concurrent with, or after the onset of a sublethal dose of virulent L. monocytogenes. Kinetics of bacterial growth in mice were not altered if 2-DG was applied concurrently or after the start of the infection. In contrast, mice exposed to 2-DG prior to infection demonstrated an enhanced resistance to the listeria challenge. The enhanced bacterial clearance in vivo could not be explained by 2-DG exerting a toxic effect on the listeria, based on the results of two experiments. First, 2-DG did not inhibit listeria replication in trypticase soy broth. Second, replication of L. monocytogenes was not inhibited in bone marrow-derived macrophage cultures exposed to 2-DG. Production of neopterin and lysozyme, indicators of macrophage activation, were enhanced following exposure to 2-DG, which correlated with the increased resistance to L. monocytogenes. These results support the contention that the host response to 2-DG-induced metabolic stress can influence the capacity of the immune system to resist infection by certain classes of microbial pathogens.

  4. Stearidonic and γ-linolenic acids in echium oil improves glucose disposal in insulin resistant monkeys.

    Science.gov (United States)

    Kavanagh, K; Flynn, D M; Jenkins, K A; Wilson, M D; Chilton, F H

    2013-07-01

    Echium oil (EO) contains stearidonic acid (18:4), a n-3 polyunsaturated fatty acids (PUFAs), and gamma-linolenic acids (18:3), a n-6 PUFA that can be converted to long chain (LC)-PUFAs. We aimed to compare a safflower oil (SO)-enriched diet to EO- and fish oil (FO)-enriched diets on circulating and tissue PUFAs levels and glycemic, inflammatory, and cardiovascular health biomarkers in insulin resistant African green monkeys. In a Latin-square cross-over study, eight monkeys consumed matched diets for 6 weeks with 3-week washout periods. Monkeys consuming FO had significantly higher levels of n-3 LC-PUFAs and EO supplementation resulted in higher levels of circulating n-3 LC-PUFAs and a significant increase in dihomo-gamma linolenic acid (DGLA) in red blood cells and muscle. Glucose disposal was improved after EO consumption. These data suggest that PUFAs in EO supplementation have the capacity to alter circulating, RBC and muscle LC-PUFA levels and improve glucose tolerance in insulin-resistant monkeys. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Insulin resistance and reduced brain glucose metabolism in the aetiology of Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Amy L. Berger

    2016-12-01

    Full Text Available Significant epidemiological and clinical evidence has emerged that suggests Alzheimer’s disease (AD can be added to the list of chronic illnesses that are primarily caused by modern diets and lifestyles at odds with human physiology. High intakes of refined carbohydrates insufficient physical activity, suboptimal sleep quantity and quality, and other factors that may contribute to insulin resistance combine to create a perfect storm of glycation and oxidative stress in the brain. Specific neurons lose the ability to metabolise and harness energy from glucose, ultimately resulting in neuronal degeneration and death. Simultaneously, chronic peripheral hyperinsulinaemia prevents ketogenesis, thus depriving struggling neurons of a highly efficient alternative fuel substrate. The intimate association between type 2 diabetes and AD suggests that they have common underlying causes, namely insulin resistance and perturbed glucose metabolism. Preclinical evidence of AD is detectable decades before over symptoms appear, indicating that AD progresses over time, with observable signs manifesting only after the brain’s compensatory mechanisms have failed and widespread neuronal atrophy begins to interfere with cognition and performance of daily life tasks. That dietary and environmental triggers play pivotal roles in causing AD suggests that nutrition and lifestyle based interventions may hold the key to ameliorating or preventing this debilitating condition for which conventional pharmaceutical treatments are largely ineffective. Results from small scale clinical studies indicate that dietary and lifestyle strategies may be effective for reversing dementia and cognitive impairment. Increased research efforts should be dedicated towards this promising avenue in the future.

  6. Vitamin D, sub-inflammation and insulin resistance. A window on a potential role for the interaction between bone and glucose metabolism.

    Science.gov (United States)

    Garbossa, Stefania Giuliana; Folli, Franco

    2017-06-01

    Vitamin D is a key hormone involved in the regulation of calcium/phosphorous balance and recently it has been implicated in the pathogenesis of sub-inflammation, insulin resistance and obesity. The two main forms of vitamin D are cholecalciferol (Vitamin D3) and ergocalciferol (Vitamin D2): the active form (1,25-dihydroxyvitamin D) is the result of two hydroxylations that take place in liver, kidney, pancreas and immune cells. Vitamin D increases the production of some anti-inflammatory cytokines and reduces the release of some pro-inflammatory cytokines. Low levels of Vitamin D are also associated with an up-regulation of TLRs expression and a pro-inflammatory state. Regardless of the effect on inflammation, Vitamin D seems to directly increase insulin sensitivity and secretion, through different mechanisms. Considering the importance of low grade chronic inflammation in metabolic syndrome, obesity and diabetes, many authors hypothesized the involvement of this nutrient/hormone in the pathogenesis of these diseases. Vitamin D status could alter the balance between pro and anti-inflammatory cytokines and thus affect insulin action, lipid metabolism and adipose tissue function and structure. Numerous studies have shown that Vitamin D concentrations are inversely associated with pro-inflammatory markers, insulin resistance, glucose intolerance and obesity. Interestingly, some longitudinal trials suggested also an inverse association between vitamin D status and incident type 2 diabetes mellitus. However, vitamin D supplementation in humans showed controversial effects: with some studies demonstrating improvements in insulin sensitivity, glucose and lipid metabolism while others showing no beneficial effect on glycemic control and on inflammation. In conclusion, although the evidences of a significant role of Vitamin D on inflammation, insulin resistance and insulin secretion in the pathogenesis of obesity, metabolic syndrome and type 2 diabetes, its potential

  7. UDP-glucose ceramide glucosyltransferase activates AKT, promoted proliferation, and doxorubicin resistance in breast cancer cells.

    Science.gov (United States)

    Wegner, Marthe-Susanna; Schömel, Nina; Gruber, Lisa; Örtel, Stephanie Beatrice; Kjellberg, Matti Aleksi; Mattjus, Peter; Kurz, Jennifer; Trautmann, Sandra; Peng, Bing; Wegner, Martin; Kaulich, Manuel; Ahrends, Robert; Geisslinger, Gerd; Grösch, Sabine

    2018-03-17

    The UDP-glucose ceramide glucosyltransferase (UGCG) is a key enzyme in the synthesis of glycosylated sphingolipids, since this enzyme generates the precursor for all complex glycosphingolipids (GSL), the GlcCer. The UGCG has been associated with several cancer-related processes such as maintaining cancer stem cell properties or multidrug resistance induction. The precise mechanisms underlying these processes are unknown. Here, we investigated the molecular mechanisms occurring after UGCG overexpression in breast cancer cells. We observed alterations of several cellular properties such as morphological changes, which enhanced proliferation and doxorubicin resistance in UGCG overexpressing MCF-7 cells. These cellular effects seem to be mediated by an altered composition of glycosphingolipid-enriched microdomains (GEMs), especially an accumulation of globotriaosylceramide (Gb3) and glucosylceramide (GlcCer), which leads to an activation of Akt and ERK1/2. The induction of the Akt and ERK1/2 signaling pathway results in an increased gene expression of multidrug resistance protein 1 (MDR1) and anti-apoptotic genes and a decrease of pro-apoptotic gene expression. Inhibition of the protein kinase C (PKC) and phosphoinositide 3 kinase (PI3K) reduced MDR1 gene expression. This study discloses how changes in UGCG expression impact several cellular signaling pathways in breast cancer cells resulting in enhanced proliferation and multidrug resistance.

  8. ROS-mediated glucose metabolic reprogram induces insulin resistance in type 2 diabetes.

    Science.gov (United States)

    Dong, Kelei; Ni, Hua; Wu, Meiling; Tang, Ziqing; Halim, Michael; Shi, Dongyun

    2016-08-05

    Oxidative stress is known to contribute to insulin resistance in diabetes, however the mechanism is not clear. Here we show that reactive oxygen species (ROS) could reprogram the glucose metabolism through upregulating the pentose pathway so as to induce insulin resistance in type 2 diabetes (T2DM). By using streptozotocin-high fat diet (STZ-HFD) induced T2DM in rats, we show that diabetic rats exhibited high level of oxidative stress accompanied with insulin resistance. Hypoxia inducible factor (HIF-1α) protein expression as well as its downstream target glucokinase (GK), were upregulated; The glycogen synthesis increased accordingly; However the glycolysis was inhibited as indicated by decreased phosphofructokinase-1 (PFK-1), pyruvate kinase (PK), phospho-PFK-2/PFK-2 (p-PFK-2/PFK-2) ratio, lactate dehydrogenase (LDH) and pyruvate dehydrogenase kinase (PDK); Pyruvate dehydrogenase (PDH) which promotes pyruvate to generate acetyl-CoA declined as well. While phospho-acetyl-CoA carboxylase/acetyl-CoA carboxylase (p-ACC/ACC) ratio increased, meaning that lipid beta-oxidation increased. The pentose pathway was activated as indicated by increased G6PD activity and NADPH level. Our results suggest that diabetic rats countervail ROS stress through increasing pentose pathway, and reprogram the energy metabolic pathway from glycolysis into lipid oxidation in order to compensate the ATP requirement of the body, which causes insulin resistance. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Effects of glucose, insulin, and insulin resistance on cerebral 18F-FDG distribution in cognitively normal older subjects.

    Science.gov (United States)

    Ishibashi, Kenji; Onishi, Airin; Fujiwara, Yoshinori; Ishiwata, Kiichi; Ishii, Kenji

    2017-01-01

    Increasing plasma glucose levels and insulin resistance can alter the distribution pattern of fluorine-18-labeled fluorodeoxyglucose (18F-FDG) in the brain and relatively reduce 18F-FDG uptake in Alzheimer's disease (AD)-related hypometabolic regions, leading to the appearance of an AD-like pattern. However, its relationship with plasma insulin levels is unclear. We aimed to compare the effects of plasma glucose levels, plasma insulin levels and insulin resistance on the appearance of the AD-like pattern in 18F-FDG images. Fifty-nine cognitively normal older subjects (age = 75.7 ± 6.4 years) underwent 18F-FDG positron emission tomography along with measurement of plasma glucose and insulin levels. As an index of insulin resistance, the Homeostasis model assessment of Insulin Resistance (HOMA-IR) was calculated. Plasma glucose levels, plasma insulin levels, and HOMA-IR were 102.2 ± 8.1 mg/dL, 4.1 ± 1.9 μU/mL, and 1.0 ± 0.5, respectively. Whole-brain voxelwise analysis showed a negative correlation of 18F-FDG uptake with plasma glucose levels in the precuneus and lateral parietotemporal regions (cluster-corrected p insulin levels or HOMA-IR. In the significant cluster, 18F-FDG uptake decreased by approximately 4-5% when plasma glucose levels increased by 20 mg/dL. In the precuneus region, volume-of-interest analysis confirmed a negative correlation of 18F-FDG uptake with plasma glucose levels (r = -0.376, p = 0.002), and no correlation with plasma insulin levels (r = 0.156, p = 0.12) or HOMA-IR (r = 0.096, p = 0.24). This study suggests that, of the three parameters, plasma glucose levels have the greatest effect on the appearance of the AD-like pattern in 18F-FDG images.

  10. Neuronal LRP1 regulates glucose metabolism and insulin signaling in the brain.

    Science.gov (United States)

    Liu, Chia-Chen; Hu, Jin; Tsai, Chih-Wei; Yue, Mei; Melrose, Heather L; Kanekiyo, Takahisa; Bu, Guojun

    2015-04-08

    Alzheimer's disease (AD) is a neurological disorder characterized by profound memory loss and progressive dementia. Accumulating evidence suggests that Type 2 diabetes mellitus, a metabolic disorder characterized by insulin resistance and glucose intolerance, significantly increases the risk for developing AD. Whereas amyloid-β (Aβ) deposition and neurofibrillary tangles are major histological hallmarks of AD, impairment of cerebral glucose metabolism precedes these pathological changes during the early stage of AD and likely triggers or exacerbates AD pathology. However, the mechanisms linking disturbed insulin signaling/glucose metabolism and AD pathogenesis remain unclear. The low-density lipoprotein receptor-related protein 1 (LRP1), a major apolipoprotein E receptor, plays critical roles in lipoprotein metabolism, synaptic maintenance, and clearance of Aβ in the brain. Here, we demonstrate that LRP1 interacts with the insulin receptor β in the brain and regulates insulin signaling and glucose uptake. LRP1 deficiency in neurons leads to impaired insulin signaling as well as reduced levels of glucose transporters GLUT3 and GLUT4. Consequently, glucose uptake is reduced. By using an in vivo microdialysis technique sampling brain glucose concentration in freely moving mice, we further show that LRP1 deficiency in conditional knock-out mice resulted in glucose intolerance in the brain. We also found that hyperglycemia suppresses LRP1 expression, which further exacerbates insulin resistance, glucose intolerance, and AD pathology. As loss of LRP1 expression is seen in AD brains, our study provides novel insights into insulin resistance in AD. Our work also establishes new targets that can be explored for AD prevention or therapy. Copyright © 2015 the authors 0270-6474/15/355851-09$15.00/0.

  11. Guava leaf extracts promote glucose metabolism in SHRSP.Z-Leprfa/Izm rats by improving insulin resistance in skeletal muscle.

    Science.gov (United States)

    Guo, Xiangyu; Yoshitomi, Hisae; Gao, Ming; Qin, Lingling; Duan, Ying; Sun, Wen; Xu, Tunhai; Xie, Peifeng; Zhou, Jingxin; Huang, Liansha; Liu, Tonghua

    2013-03-01

    Metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM) have been associated with insulin-resistance; however, the effective therapies in improving insulin sensitivity are limited. This study is aimed at investigating the effect of Guava Leaf (GL) extracts on glucose tolerance and insulin resistance in SHRSP.Z-Leprfa/Izm rats (SHRSP/ZF), a model of spontaneously metabolic syndrome. Male rats at 7 weeks of age were administered with vehicle water or treated by gavage with 2 g/kg GL extracts daily for six weeks, and their body weights, water and food consumption, glucose tolerance, and insulin resistance were measured. Compared with the controls, treatment with GL extracts did not modulate the amounts of water and food consumption, but significantly reduced the body weights at six weeks post treatment. Treatment with GL extracts did not alter the levels of fasting plasma glucose and insulin, but significantly reduced the levels of plasma glucose at 60 and 120 min post glucose challenge, also reduced the values of AUC and quantitative insulin sensitivity check index (QUICKI) at 42 days post treatment. Furthermore, treatment with GL extracts promoted IRS-1, AKT, PI3Kp85 expression, then IRS-1, AMKP, and AKT308, but not AKT473, phosphorylation, accompanied by increasing the ratios of membrane to total Glut 4 expression and adiponectin receptor 1 transcription in the skeletal muscles. These data indicated that GL extracts improved glucose metabolism and insulin sensitivity in the skeletal muscles of rats by modulating the insulin-related signaling.

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

    Science.gov (United States)

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

    2013-01-01

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

  13. Skeletal Muscle TRIB3 Mediates Glucose Toxicity in Diabetes and High- Fat Diet-Induced Insulin Resistance.

    Science.gov (United States)

    Zhang, Wei; Wu, Mengrui; Kim, Teayoun; Jariwala, Ravi H; Garvey, W John; Luo, Nanlan; Kang, Minsung; Ma, Elizabeth; Tian, Ling; Steverson, Dennis; Yang, Qinglin; Fu, Yuchang; Garvey, W Timothy

    2016-08-01

    In the current study, we used muscle-specific TRIB3 overexpressing (MOE) and knockout (MKO) mice to determine whether TRIB3 mediates glucose-induced insulin resistance in diabetes and whether alterations in TRIB3 expression as a function of nutrient availability have a regulatory role in metabolism. In streptozotocin diabetic mice, TRIB3 MOE exacerbated, whereas MKO prevented, glucose-induced insulin resistance and impaired glucose oxidation and defects in insulin signal transduction compared with wild-type (WT) mice, indicating that glucose-induced insulin resistance was dependent on TRIB3. In response to a high-fat diet, TRIB3 MOE mice exhibited greater weight gain and worse insulin resistance in vivo compared with WT mice, coupled with decreased AKT phosphorylation, increased inflammation and oxidative stress, and upregulation of lipid metabolic genes coupled with downregulation of glucose metabolic genes in skeletal muscle. These effects were prevented in the TRIB3 MKO mice relative to WT mice. In conclusion, TRIB3 has a pathophysiological role in diabetes and a physiological role in metabolism. Glucose-induced insulin resistance and insulin resistance due to diet-induced obesity both depend on muscle TRIB3. Under physiological conditions, muscle TRIB3 also influences energy expenditure and substrate metabolism, indicating that the decrease and increase in muscle TRIB3 under fasting and nutrient excess, respectively, are critical for metabolic homeostasis. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  14. Abnormal release of incretins and cortisol after oral glucose in subjects with insulin-resistant myotonic dystrophy

    DEFF Research Database (Denmark)

    Johansson, Asa; Olsson, Tommy; Cederquist, Kristina

    2002-01-01

    OBJECTIVE: Although the incretins, gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), as well as glucagon and cortisol, are known to influence islet function, the role of these hormones in conditions of insulin resistance and development of type 2 diabetes is unknown...... response. Furthermore, cortisol and ACTH levels increased paradoxically in patients after glucose; this was more pronounced in patients with long CTG repeat expansions. CONCLUSIONS: This study showed that the GLP-1 and ACTH/cortisol responses to oral glucose are abnormal in insulin-resistant DM1 patients...

  15. Glucose infusion causes insulin resistance in skeletal muscle of rats without changes in Akt and AS160 phosphorylation.

    Science.gov (United States)

    Hoy, Andrew J; Bruce, Clinton R; Cederberg, Anna; Turner, Nigel; James, David E; Cooney, Gregory J; Kraegen, Edward W

    2007-11-01

    Hyperglycemia is a defining feature of Type 1 and 2 diabetes. Hyperglycemia also causes insulin resistance, and our group (Kraegen EW, Saha AK, Preston E, Wilks D, Hoy AJ, Cooney GJ, Ruderman NB. Am J Physiol Endocrinol Metab Endocrinol Metab 290: E471-E479, 2006) has recently demonstrated that hyperglycemia generated by glucose infusion results in insulin resistance after 5 h but not after 3 h. The aim of this study was to investigate possible mechanism(s) by which glucose infusion causes insulin resistance in skeletal muscle and in particular to examine whether this was associated with changes in insulin signaling. Hyperglycemia (~10 mM) was produced in cannulated male Wistar rats for up to 5 h. The glucose infusion rate required to maintain this hyperglycemia progressively lessened over 5 h (by 25%, P < 0.0001 at 5 h) without any alteration in plasma insulin levels consistent with the development of insulin resistance. Muscle glucose uptake in vivo (44%; P < 0.05) and glycogen synthesis rate (52%; P < 0.001) were reduced after 5 h compared with after 3 h of infusion. Despite these changes, there was no decrease in the phosphorylation state of multiple insulin signaling intermediates [insulin receptor, Akt, AS160 (Akt substrate of 160 kDa), glycogen synthase kinase-3beta] over the same time course. In isolated soleus strips taken from control or 1- or 5-h glucose-infused animals, insulin-stimulated 2-deoxyglucose transport was similar, but glycogen synthesis was significantly reduced in the 5-h muscle sample (68% vs. 1-h sample; P < 0.001). These results suggest that the reduced muscle glucose uptake in rats after 5 h of acute hyperglycemia is due more to the metabolic effects of excess glycogen storage than to a defect in insulin signaling or glucose transport.

  16. The patterns of glucose tolerance and insulin resistance among rural Chinese twin children, adolescents, and young adults.

    Science.gov (United States)

    Wang, Guoying; Wang, Binyan; Ouyang, Fengxiu; Liu, Xue; Tang, Gengfu; Xing, Houxun; Li, Zhiping; Xu, Xiping; Wang, Xiaobin

    2010-12-01

    Pubertal insulin resistance (IR) is well recognized; but little data are available for glucose and insulin pattern from a large, unselected lean population. This report describes the age- and sex-specific distributions of glucose tolerance and IR in a rural Chinese twin population. This report includes 4488 subjects aged 6 to 24 years. The primary variables of interest are fasting plasma glucose, 2-hour postload plasma glucose (2-h PG), fasting serum insulin, 2-hour postload insulin, and the homeostatic model assessment for IR. Age- and sex-specific patterns for the primary variables are described using smoothing plot, arithmetic or geometric mean, and percentiles. There is an increase in fasting plasma glucose, 2-h PG, and IR during puberty (10-19 years) and a return to prepuberty level by the age of 20 years. Insulin resistance peaks at around the age of 14 years in girls and 16 years in boys. Two-hour postload plasma glucose and 2-hour postload insulin are higher in girls than in boys from early puberty, and the sex differences are more pronounced afterward. Moreover, the prevalence of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) increases after puberty and is higher in girls than in boys. In this community-based, nonobese rural Chinese twin population, we observed sex-specific remarkable pubertal surge of IR and modest increase in plasma glucose as well as increasing prevalence of IFG and IGT with age. Notably, females had higher 2-h PG and higher prevalence of IFG and IGT. Our study underscored that adolescence (even more so in females) is a critical period for developing IR and prediabetes. Copyright © 2010 Elsevier Inc. All rights reserved.

  17. Glucose alteration and insulin resistance in asymptomatic obese children and adolescents.

    Science.gov (United States)

    Assunção, Silvana Neves Ferraz de; Boa Sorte, Ney Christian Amaral; Alves, Crésio de Aragão Dantas; Mendes, Patricia S Almeida; Alves, Carlos Roberto Brites; Silva, Luciana Rodrigues

    2017-08-26

    Obesity is associated with the abnormal glucose metabolism preceding type 2 diabetes mellitus. Thus, further investigation on the prediction of this lethal outcome must be sought. The objective was the profile glycemic assessment of asymptomatic obese children and adolescents from Salvador, Brazil. A fasting venous blood sample was obtained from 90 consecutive obese individuals aged 8-18 years, of both sexes, for laboratory determinations of glycated hemoglobin, basal insulin, and the Homeostasis Model Assessment Insulin Resistance index. The clinical evaluation included weight, height, waist circumference, assessment of pubertal development, and acanthosis nigricans research. The body mass index/age indicator was used for the severity of overweight assessment. Glycemic alterations were evidenced clinically and biochemically, although these individuals had no complaints or symptoms related to blood sugar levels. Quantitative and qualitative variables were respectively expressed measures of central tendency/dispersion and simple/relative frequency, using the SPSS, version 20.0. A p-value <0.05 was considered significant. Notably, this study found a high prevalence of glucose and insulin disorders in asymptomatic obese children and adolescents. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  18. Lactate promotes resistance to glucose starvation via upregulation of Bcl-2 mediated by mTOR activation.

    Science.gov (United States)

    Huang, Chen; Sheng, Shile; Li, Rui; Sun, Xiaoguang; Liu, Jianju; Huang, Gang

    2015-02-01

    Solid tumors grow faster and need more glucose than normal tissue; however, due to poor angiogenesis and excessive growth, tumors remote from blood vessels are always under glucose starvation. Even so, cancer cells remain alive in vivo. Thus, making cancer cells sensitive to glucose depletion may potentially provide an effective strategy for cancer intervention. Tumors that obtain sufficient glucose generate a large amount of lactate. Therefore, we proposed that lactate, a tumor microenvironment factor, may allow cancer cells to develop resistance to glucose starvation-induced death. We cultured cancer cells in no-glucose medium and added lactate to the medium. During the experiment, lactate helped cancer cells to escape from glucose starvation-induced cell death, without using lactate as an energy substrate, resulting in activation of Akt through PI3K. Akt activation plays a central role in cell growth through the activation of mammalian target of rapamycin (mTOR). Alteration of the PI3K/Akt/mTOR signaling pathway by inhibiting apoptosis induced specific upregulation of B-cell lymphoma 2 (Bcl-2) through translational control. In conclusion, this study showed that lactate rescues cancer cells from glucose starvation-induced cell death through regulation of the PI3K/Akt/mTOR/Bcl-2 signaling pathway. These data suggest that lactate is an important determinant of the sensitivity of tumors to glucose starvation, and reducing lactate or inhibiting the PI3K/Akt/mTOR/Bcl-2 signaling pathway may influence the response of cancers to glucose starvation.

  19. Identification of new biomarker candidates for glucocorticoid induced insulin resistance using literature mining

    NARCIS (Netherlands)

    Fleuren, W.W.M.; Toonen, E.J.M.; Verhoeven, S.; Frijters, R.J.J.M.; Hulsen, T.; Rullmann, T.; Schaik, R. van; Vlieg, J. de; Alkema, W.

    2013-01-01

    BACKGROUND: Glucocorticoids are potent anti-inflammatory agents used for the treatment of diseases such as rheumatoid arthritis, asthma, inflammatory bowel disease and psoriasis. Unfortunately, usage is limited because of metabolic side-effects, e.g. insulin resistance, glucose intolerance and

  20. Insulin Resistance in Nondiabetic Peritoneal Dialysis Patients: Associations with Body Composition, Peritoneal Transport, and Peritoneal Glucose Absorption.

    Science.gov (United States)

    Bernardo, Ana Paula; Oliveira, Jose C; Santos, Olivia; Carvalho, Maria J; Cabrita, Antonio; Rodrigues, Anabela

    2015-12-07

    Insulin resistance has been associated with cardiovascular disease in peritoneal dialysis patients. Few studies have addressed the impact of fast transport status or dialysis prescription on insulin resistance. The aim of this study was to test whether insulin resistance is associated with obesity parameters, peritoneal transport rate, and glucose absorption. Insulin resistance was evaluated with homeostasis model assessment method (HOMA-IR), additionally corrected by adiponectin (HOMA-AD). Enrolled patients were prevalent nondiabetics attending at Santo António Hospital Peritoneal Dialysis Unit, who were free of hospitalization or infectious events in the previous 3 months (51 patients aged 50.4 ± 15.9 years, 59% women). Leptin, adiponectin, insulin-like growth factor-binding protein 1 (IGFBP-1), and daily glucose absorption were also measured. Lean tissue index, fat tissue index (FTI), and relative fat mass (rel.FM) were assessed using multifrequency bioimpedance. Patients were categorized according to dialysate to plasma creatinine ratio at 4 hours, 3.86% peritoneal equilibration test, and obesity parameters. Obesity was present in 49% of patients according to rel.FM. HOMA-IR correlated better with FTI than with body mass index. Significant correlations were found in obese, but not in nonobese patients, between HOMA-IR and leptin, leptin/adiponectin ratio (LAR), and IGFBP-1. HOMA-IR correlated with HOMA-AD, but did not correlate with glucose absorption or transport rate. There were no significant differences in insulin resistance indices, glucose absorption, and body composition parameters between fast and nonfast transporters. A total of 18 patients (35.3%) who had insulin resistance presented with higher LAR and rel.FM (7.3 [12.3, interquartile range] versus 0.7 [1.4, interquartile range], Pinsulin resistance. FTI and LAR were independent correlates of HOMA-IR in multivariate analysis adjusted for glucose absorption and small-solute transport (r=0

  1. Intolerance toward immigrants in Switzerland

    DEFF Research Database (Denmark)

    Freitag, Markus; Rapp, Carolin

    2013-01-01

    Intolerance toward immigrants has recently reached noticeable highs in Switzerland. Referring to the conflict theory, the perception of a specific group as a threat tends to lead to intolerance toward that group. The expectation of a negative relationship between threat and tolerance is neverthel......Intolerance toward immigrants has recently reached noticeable highs in Switzerland. Referring to the conflict theory, the perception of a specific group as a threat tends to lead to intolerance toward that group. The expectation of a negative relationship between threat and tolerance...

  2. Exogenous glucose administration impairs glucose tolerance and pancreatic insulin secretion during acute sepsis in non-diabetic mice.

    Directory of Open Access Journals (Sweden)

    Yoshio Watanabe

    Full Text Available OBJECTIVES: The development of hyperglycemia and the use of early parenteral feeding are associated with poor outcomes in critically ill patients. We therefore examined the impact of exogenous glucose administration on the integrated metabolic function of endotoxemic mice using our recently developed frequently sampled intravenous glucose tolerance test (FSIVGTT. We next extended our findings using a cecal ligation and puncture (CLP sepsis model administered early parenteral glucose support. METHODS: Male C57BL/6J mice, 8-12 weeks, were instrumented with chronic indwelling arterial and venous catheters. Endotoxemia was initiated with intra-arterial lipopolysaccharide (LPS; 1 mg/kg in the presence of saline or glucose infusion (100 µL/hr, and an FSIVGTT was performed after five hours. In a second experiment, catheterized mice underwent CLP and the impact of early parenteral glucose administration on glucose homeostasis and mortality was assessed over 24 hrs. MEASUREMENTS: AND MAIN RESULTS: Administration of LPS alone did not impair metabolic function, whereas glucose administration alone induced an insulin sensitive state. In contrast, LPS and glucose combined caused marked glucose intolerance and insulin resistance and significantly impaired pancreatic insulin secretion. Similarly, CLP mice receiving parenteral glucose developed fulminant hyperglycemia within 18 hrs (all > 600 mg/dl associated with increased systemic cytokine release and 40% mortality, whereas CLP alone (85 ± 2 mg/dL or sham mice receiving parenteral glucose (113 ± 3 mg/dL all survived and were not hyperglycemic. Despite profound hyperglycemia, plasma insulin in the CLP glucose-infused mice (3.7 ± 1.2 ng/ml was not higher than sham glucose infused mice (2.1 ± 0.3 ng/ml. CONCLUSIONS: The combination of parenteral glucose support and the systemic inflammatory response in the acute phase of sepsis induces profound insulin resistance and impairs compensatory pancreatic insulin

  3. Minimal cross-intolerance with nilotinib in patients with chronic myeloid leukemia in chronic or accelerated phase who are intolerant to imatinib

    Science.gov (United States)

    Hochhaus, Andreas; le Coutre, Philipp D.; Rosti, Gianantonio; Pinilla-Ibarz, Javier; Jabbour, Elias; Gillis, Kathryn; Woodman, Richard C.; Blakesley, Rick E.; Giles, Francis J.; Kantarjian, Hagop M.; Baccarani, Michele

    2011-01-01

    Nilotinib has significant efficacy in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) and in patients with CML-CP or CML in accelerated phase (CML-AP) after imatinib failure. We investigated the occurrence of cross-intolerance to nilotinib in imatinib-intolerant patients with CML. Only 1/75 (1%) patients with nonhematologic imatinib intolerance experienced a similar grade 3/4 adverse event (AE), and 3/75 (4%) experienced a similar persistent grade 2 nonhematologic AE on nilotinib. Only 7/40 (18%) patients with hematologic imatinib intolerance discontinued nilotinib, all because of grade 3/4 thrombocytopenia. Ninety percent of imatinib-intolerant patients with CML-CP who did not have complete hematologic response (CHR) at baseline (n = 52) achieved CHR on nilotinib. Nilotinib induced a major cytogenetic response in 66% and 41% of patients with imatinib-intolerant CML-CP and CML-AP (complete cytogenetic response in 51% and 30%), respectively. Minimal cross-intolerance was confirmed in patients with imatinib-intolerant CML. The favorable tolerability of nilotinib in patients with imatinib intolerance leads to alleviation of AE-related symptoms and significant and durable responses. In addition to its established clinical benefit in patients with newly diagnosed CML and those resistant to imatinib, nilotinib is effective and well-tolerated for long-term use in patients with imatinib intolerance. This study is registered at http://www.clinicaltrials.gov as NCT00471497 PMID:21467546

  4. Efficacy of 2-hour post glucose insulin levels in predicting insulin resistance in polycystic ovarian syndrome with infertility

    Directory of Open Access Journals (Sweden)

    Pikee Saxena

    2011-01-01

    Full Text Available Background : Insulin resistance (IR is central to the pathogenesis of polycystic ovarian syndrome (PCOS, but tests for determining IR are elaborate, tedious and expensive. Aims : To evaluate if "2-hour post-glucose insulin level" is an effective indicator of IR and can aid in diagnosing IR in infertile PCOS women. Settings and Design : Observational study at infertility clinic of a tertiary care center. Materials and Methods : 50 infertile women with PCOS and 20 females with tubal/male factor infertility were evaluated for the presence of IR, as defined by the fasting/2-hour post-glucose insulin levels cutoffs of >25/>41 μU/mL, respectively. The clinical, metabolic and endocrinologic profile was determined in both the groups. Statistical Analysis : Statistical analysis was performed using SPSS (Chicago, IL, USA. Results : Body mass index, post load glucose, insulin, glucose/insulin ratio, area under curve (AUC of glucose and insulin and insulinogenic index were significantly lower in the controls as compared to the PCOS group. "2-hour post-glucose insulin levels" were elevated in 88% of PCOS individuals but were normal in all females not suffering from PCOS. These levels significantly correlated with AUC of glucose and insulin, and insulinogenic index and inversely correlated with 2-hour glucose to insulin ratio (r=0.827, 0.749 and −0.732, respectively. Conclusions : "2-hour post-glucose insulin levels" appears to be a good indicator of IR. It can be a useful tool, especially in low resource setting where a single sample can confirm the diagnosis, thus reducing cost and repeat visits.

  5. Sirolimus in patients with clinically active systemic lupus erythematosus resistant to, or intolerant of, conventional medications: a single-arm, open-label, phase 1/2 trial.

    Science.gov (United States)

    Lai, Zhi-Wei; Kelly, Ryan; Winans, Thomas; Marchena, Ivan; Shadakshari, Ashwini; Yu, Julie; Dawood, Maha; Garcia, Ricardo; Tily, Hajra; Francis, Lisa; Faraone, Stephen V; Phillips, Paul E; Perl, Andras

    2018-03-24

    Patients with systemic lupus erythematosus have T-cell dysfunction that has been attributed to the activation of the mammalian target of rapamycin (mTOR). Rapamycin inhibits antigen-induced T-cell proliferation and has been developed as a medication under the generic designation of sirolimus. We assessed safety, tolerance, and efficacy of sirolimus in a prospective, biomarker-driven, open-label clinical trial. We did a single-arm, open-label, phase 1/2 trial of sirolimus in patients with active systemic lupus erythematosus disease unresponsive to, or intolerant of, conventional medications at the State University of New York Upstate Medical University (Syracuse, NY, USA). Eligible participants (aged ≥18 years) had active systemic lupus erythematosus fulfilling four or more of 11 diagnostic criteria defined by the American College of Rheumatology. We excluded patients with allergy or intolerance to sirolimus, patients with life-threatening manifestations of systemic lupus erythematosus, proteinuria, a urine protein to creatinine ratio higher than 0·5, anaemia, leucopenia, or thrombocytopenia. Patients received oral sirolimus at a starting dose of 2 mg per day, with dose adjusted according to tolerance and to maintain a therapeutic range of 6-15 ng/mL. Patients were treated with sirolimus for 12 months. Safety outcomes included tolerance as assessed by the occurrence of common side-effects. The primary efficacy endpoint was decrease in disease activity, assessed using the British Isles Lupus Assessment Group (BILAG) index and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Blood samples of 56 matched healthy individuals were obtained as controls for immunobiological outcomes monitored at each visit. The primary efficacy endpoint was assessed in all patients who completed 12 months of treatment, and all patients who received at least one dose of treatment were included in the safety analyses. This trial is registered with Clinical

  6. Biological and Clinical Study of 6-Deoxy-6-Iodo-D-Glucose: a iodinated tracer of glucose transport and of insulin-resistance in human

    International Nuclear Information System (INIS)

    Barone-Rochette, Gilles

    2013-01-01

    Insulin resistance (IR), characterized by a depressed cellular sensitivity to insulin in insulin-sensitive organs, is a central feature to obesity, the metabolic syndrome, and diabetes mellitus and leads to increase cardiovascular diseases, particularly heart failure. All these events are today serious public health problems. But actually, there is no simple tool to measure insulin resistance. The gold standard technique remains the hyperinsulinemic euglycemic clamp. However, the complexity and length of this technique render it unsuitable for routine clinical use. Many methods or index have been proposed to assess insulin resistance in human, but none have shown enough relevance to be used in clinical use. The U1039 INSERM unit previously has validated a new tracer of glucose transport, radiolabelled with 123 iodine and has developed a fast and simple imaging protocol with a small animal gamma camera, which allows the obtaining of an IR index for each organ, showing more discriminating for the heart. The project of my thesis was the human transfer of this measurement technique, perfectly validated in animal. The first part of this thesis evaluated to tolerance, in vivo kinetics, distribution and dosimetry of novel tracer of glucose transport, the [ 123 I]-6DIG. The safeties of new tracer and measurement technique were adequate. There were no adverse effects with excellent tolerance of the whole protocol. 6DIG eliminating was fast, primarily in the urine and complete within 72 h. The effective whole-body absorbed dose for a complete scan with injection of 92.5 * 2 MBq was between 3 to 4 mSv. The second part of this thesis evaluated in human feasibility and reproducibility of the measurement technique validated in animal. The third part showed techniques used to allow human transfer of this method. The study protocol was applied on 12 subjects (healthy volunteers (n=6) and type 2 diabetic patients (n=6)). With a method adapted to measure in humans, we determined an

  7. Absence of Carbohydrate Response Element Binding Protein in Adipocytes Causes Systemic Insulin Resistance and Impairs Glucose Transport.

    Science.gov (United States)

    Vijayakumar, Archana; Aryal, Pratik; Wen, Jennifer; Syed, Ismail; Vazirani, Reema P; Moraes-Vieira, Pedro M; Camporez, Joao Paulo; Gallop, Molly R; Perry, Rachel J; Peroni, Odile D; Shulman, Gerald I; Saghatelian, Alan; McGraw, Timothy E; Kahn, Barbara B

    2017-10-24

    Lower adipose-ChREBP and de novo lipogenesis (DNL) are associated with insulin resistance in humans. Here, we generated adipose-specific ChREBP knockout (AdChREBP KO) mice with negligible sucrose-induced DNL in adipose tissue (AT). Chow-fed AdChREBP KO mice are insulin resistant with impaired insulin action in the liver, muscle, and AT and increased AT inflammation. HFD-fed AdChREBP KO mice are also more insulin resistant than controls. Surprisingly, adipocytes lacking ChREBP display a cell-autonomous reduction in insulin-stimulated glucose transport that is mediated by impaired Glut4 translocation and exocytosis, not lower Glut4 levels. AdChREBP KO mice have lower levels of palmitic acid esters of hydroxy stearic acids (PAHSAs) in serum, and AT. 9-PAHSA supplementation completely rescues their insulin resistance and AT inflammation. 9-PAHSA also normalizes impaired glucose transport and Glut4 exocytosis in ChREBP KO adipocytes. Thus, loss of adipose-ChREBP is sufficient to cause insulin resistance, potentially by regulating AT glucose transport and flux through specific lipogenic pathways. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  8. Absence of Carbohydrate Response Element Binding Protein in Adipocytes Causes Systemic Insulin Resistance and Impairs Glucose Transport

    Directory of Open Access Journals (Sweden)

    Archana Vijayakumar

    2017-10-01

    Full Text Available Lower adipose-ChREBP and de novo lipogenesis (DNL are associated with insulin resistance in humans. Here, we generated adipose-specific ChREBP knockout (AdChREBP KO mice with negligible sucrose-induced DNL in adipose tissue (AT. Chow-fed AdChREBP KO mice are insulin resistant with impaired insulin action in the liver, muscle, and AT and increased AT inflammation. HFD-fed AdChREBP KO mice are also more insulin resistant than controls. Surprisingly, adipocytes lacking ChREBP display a cell-autonomous reduction in insulin-stimulated glucose transport that is mediated by impaired Glut4 translocation and exocytosis, not lower Glut4 levels. AdChREBP KO mice have lower levels of palmitic acid esters of hydroxy stearic acids (PAHSAs in serum, and AT. 9-PAHSA supplementation completely rescues their insulin resistance and AT inflammation. 9-PAHSA also normalizes impaired glucose transport and Glut4 exocytosis in ChREBP KO adipocytes. Thus, loss of adipose-ChREBP is sufficient to cause insulin resistance, potentially by regulating AT glucose transport and flux through specific lipogenic pathways.

  9. Assessment of insulin action in insulin-dependent diabetes mellitus using [6(14)C]glucose, [3(3)H]glucose, and [2(3)H]glucose. Differences in the apparent pattern of insulin resistance depending on the isotope used

    International Nuclear Information System (INIS)

    Bell, P.M.; Firth, R.G.; Rizza, R.A.

    1986-01-01

    To determine whether [2(3)H], [3(3)H], and [6(14)C]glucose provide an equivalent assessment of glucose turnover in insulin-dependent diabetes mellitus (IDDM) and nondiabetic man, glucose utilization rates were measured using a simultaneous infusion of these isotopes before and during hyperinsulinemic euglycemic clamps. In the nondiabetic subjects, glucose turnover rates determined with [6(14)C]glucose during insulin infusion were lower (P less than 0.02) than those determined with [2(3)H]glucose and higher (P less than 0.01) than those determined with [3(3)H]glucose. In IDDM, glucose turnover rates measured with [6(14)C]glucose during insulin infusion were lower (P less than 0.05) than those determined with [2(3)H]glucose, but were not different from those determined with [3(3)H]glucose. All three isotopes indicated the presence of insulin resistance. However, using [3(3)H]glucose led to the erroneous conclusion that glucose utilization was not significantly decreased at high insulin concentrations in the diabetic patients. [6(14)C] and [3(3)H]glucose but not [2(3)H]glucose indicated impairment in insulin-induced suppression of glucose production. These results indicate that tritiated isotopes do not necessarily equally reflect the pattern of glucose metabolism in diabetic and nondiabetic man

  10. Genetics Home Reference: lysinuric protein intolerance

    Science.gov (United States)

    ... Home Health Conditions Lysinuric protein intolerance Lysinuric protein intolerance Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Lysinuric protein intolerance is a disorder caused by the body's inability ...

  11. Genetics Home Reference: hereditary fructose intolerance

    Science.gov (United States)

    ... Home Health Conditions Hereditary fructose intolerance Hereditary fructose intolerance Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Hereditary fructose intolerance is a condition that affects a person's ability ...

  12. Intolerable Intolerance: Toxic Xenophobia and Pedagogy of Resistance

    Science.gov (United States)

    Jones, Rachel Bailey

    2011-01-01

    In this paper, the author examines the mobilization and regulation of toxic xenophobia in the post-September 11th era. The graphic posters from the far-right, anti-immigration Swiss UDC party are examined along with artistic responses to this graphic xenophobia. The paper argues that using the visual forms of xenophobia and the artistic responses…

  13. Pulsatile insulin secretion, impaired glucose tolerance and type 2 diabetes.

    Science.gov (United States)

    Satin, Leslie S; Butler, Peter C; Ha, Joon; Sherman, Arthur S

    2015-04-01

    Type 2 diabetes (T2DM) results when increases in beta cell function and/or mass cannot compensate for rising insulin resistance. Numerous studies have documented the longitudinal changes in metabolism that occur during the development of glucose intolerance and lead to T2DM. However, the role of changes in insulin secretion, both amount and temporal pattern, has been understudied. Most of the insulin secreted from pancreatic beta cells of the pancreas is released in a pulsatile pattern, which is disrupted in T2DM. Here we review the evidence that changes in beta cell pulsatility occur during the progression from glucose intolerance to T2DM in humans, and contribute significantly to the etiology of the disease. We review the evidence that insulin pulsatility improves the efficacy of secreted insulin on its targets, particularly hepatic glucose production, but also examine evidence that pulsatility alters or is altered by changes in peripheral glucose uptake. Finally, we summarize our current understanding of the biophysical mechanisms responsible for oscillatory insulin secretion. Understanding how insulin pulsatility contributes to normal glucose homeostasis and is altered in metabolic disease states may help improve the treatment of T2DM. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Pulsatile insulin secretion, impaired glucose tolerance and type 2 diabetes

    Science.gov (United States)

    Satin, Leslie S.; Butler, Peter C.; Ha, Joon; Sherman, Arthur S.

    2015-01-01

    Type 2 diabetes (T2DM) results when increases in beta cell function and/or mass cannot compensate for rising insulin resistance. Numerous studies have documented the longitudinal changes in metabolism that occur during the development of glucose intolerance and lead to T2DM. However, the role of changes in insulin secretion, both amount and temporal pattern has been understudied. Most of the insulin secreted from pancreatic beta cells of the pancreas is released in a pulsatile pattern, which is disrupted in T2DM. Here we review the evidence that changes in beta cell pulsatility occur during the progression from glucose intolerance to T2DM in humans, and contribute significantly to the etiology of the disease. We review the evidence that insulin pulsatility improves the efficacy of secreted insulin on its targets, particularly hepatic glucose production, but also examine evidence that pulsatility alters or is altered by changes in peripheral glucose uptake. Finally, we summarize our current understanding of the biophysical mechanisms responsible for oscillatory insulin secretion. Understanding how insulin pulsatility contributes to normal glucose homeostasis and is altered in metabolic disease states may help improve the treatment of T2DM. PMID:25637831

  15. Insulin resistance and the transcription of the glucose-6-phosphatase gene in newborn dogs.

    Science.gov (United States)

    Feng, B C; Li, J; Kliegman, R M

    1997-04-01

    In the present report changes in the mRNA level of glucose-6-phosphatase (G6Pase; EC 3.1.39) in newborn and adult dogs in vivo were studied to further test the hypotheses that neonatal hyperglycemia may be due to unsuppressed gluconeogenesis by insulin and that the antidiabetic role of insulin-like growth factor-1 (IGF-1) may be intact in newborn dogs who have consistently demonstrated insulin resistance. Our results were the following: (i) Both renal and hepatic G6Pase mRNA were expressed at birth and increased with time during a 24-h period of fasting after birth. (ii) The renal G6Pase mRNA levels in newborn dogs did not respond to either insulin or epinephrine. (iii) Hyperinsulinemia lowered the liver G6Pase mRNA by only 16.3% in newborn dogs, but reduced the liver G6Pase mRNA to an undetectable level in adult dogs. (iv) Hyperglycemia decreased the hepatic G6Pase mRNA by 14.3% in newborn dogs under hyperinsulinemia. (v) Infused epinephrine did not elevate the hepatic G6Pase mRNA level in newborn dogs in the presence of hyperglycemia and hyperinsulinemia. (vi) In newborn dogs, hyper-IGF-1 rapidly reduced the hepatic G6Pase mRNA level by 50%, and hypoglycemia was unable to elevate the hepatic G6Pase mRNA level under the hyper-IGF-1. We concluded that the reduced rate of suppression of transcription of the liver G6Pase gene by insulin in newborn dogs may reflect the unsuppressed neonatal hepatic gluconeogenesis due to insulin resistance and that the physiological roles of IGF-1 seemed to be intact in newborn dogs and may be not responsible for neonatal hyperglycemia.

  16. Effect of HCV on fasting glucose, fasting insulin and peripheral insulin resistance in first 5 years of infection.

    Science.gov (United States)

    Ahmed, Naeema; Rashid, Amir; Naveed, Abdul Khaliq; Bashir, Qudsia

    2016-02-01

    To assess the effects of hepatitis C virus infection in the first 5 years on fasting glucose, fasting insulin and peripheral insulin resistance. The case-control study was conducted at the Army Medical College, Rawalpindi, from December 2011 to November 2012, and comprised subjects recruited from a government hospital in Rawalpindi. The subjects included known cases of hepatitis C virus infection for at least 5 years, and normal healthy controls. Fasting blood samples of all the subjects were collected and analysed for serum fasting insulin and serum fasting glucose levels. Homeostatic model assessment-Insulin resistance was calculated SPSS 11 was used for statistical analysis. Of the 30 subjects, 20(66.6%) were cases, while 10(33.3%) were controls. Serum fasting glucose mean level in cases was 89.55±9.53 compared to 84.40±9.80 in the controls (p=0.188). The mean serum fasting insulin in controls was 7.52±3.23 and 6.79±3.30 in cases (p=0.567). Homeostatic model assessment-Insulin resistance level in controls was 1.60±0.76 and In the cases it was 1.49±0.74 (p=0.695). Peripheral insulin resistance and development of type 2 diabetes as a complication of hepatitis C virus infection was not likely at least within the first five years of infection.

  17. Abnormal release of incretins and cortisol after oral glucose in subjects with insulin-resistant myotonic dystrophy

    DEFF Research Database (Denmark)

    Johansson, Asa; Olsson, Tommy; Cederquist, Kristina

    2002-01-01

    . An interesting model for the study of hormonal perturbations accompanying marked insulin resistance without concomitant diabetes is myotonic dystrophy (DM1). DESIGN: The work was carried out in an out-patient setting. METHODS: An oral glucose tolerance test was performed in 18 males with DM1 and 18 controls...... to examine the release of incretins and counter-regulatory hormones. Genetic analyses were also performed in patients. RESULTS: We found that the increment in GLP-1 after oral glucose was significantly greater in patients, while there was no significant difference in GIP or glucagon responses between...... patients and controls, although long CTG repeat expansions were associated with a more pronounced GIP response. Interestingly, the GLP-1 response to oral glucose correlated with the insulin response in patients but not in controls whereas, in controls, the insulin response closely correlated with the GIP...

  18. Disease resistance conferred by expression of a gene encoding H2O2-generating glucose oxidase in transgenic potato plants.

    Science.gov (United States)

    Wu, G; Shortt, B J; Lawrence, E B; Levine, E B; Fitzsimmons, K C; Shah, D M

    1995-09-01

    Plant defense responses to pathogen infection involve the production of active oxygen species, including hydrogen peroxide (H2O2). We obtained transgenic potato plants expressing a fungal gene encoding glucose oxidase, which generates H2O2 when glucose is oxidized. H2O2 levels were elevated in both leaf and tuber tissues of these plants. Transgenic potato tubers exhibited strong resistance to a bacterial soft rot disease caused by Erwinia carotovora subsp carotovora, and disease resistance was sustained under both aerobic and anaerobic conditions of bacterial infection. This resistance to soft rot was apparently mediated by elevated levels of H2O2, because the resistance could be counteracted by exogenously added H2O2-degrading catalase. The transgenic plants with increased levels of H2O2 also exhibited enhanced resistance to potato late blight caused by Phytophthora infestans. The development of lesions resulting from infection by P. infestans was significantly delayed in leaves of these plants. Thus, the expression of an active oxygen species-generating enzyme in transgenic plants represents a novel approach for engineering broad-spectrum disease resistance in plants.

  19. Indomethacin treatment prevents diet-induced obesity and insulin resistance, but not glucose intolerance in C57BL/6J mice

    Science.gov (United States)

    OBJECTIVE: We performed experiments to examine the metabolic consequences of inhibition of cyclooxygenase (COX) activity in obesity-prone C57BL/6J mice fed a high fat/high sucrose (HF/HS) diet. RESEARCH DESIGN AND METHODS: C57BL/6J mice were fed a HF/HS diet for 7 weeks under thermoneutral conditio...

  20. Study on the insulin resistance and β-cell function in individuals with normal and those with abnormal glucose metabolism

    International Nuclear Information System (INIS)

    Wei Zikun

    2006-01-01

    Objective: To study the insulin resistance and β-cell function in individuals with normal glucose tolerance (NGT) and those with glucose metabolism dysfunction. Methods: Insulin resistance and β-cell function were studied with oral glucose tolerance test and the following parameters: 2h insulin/2h plasma glucose (2hIns/2hPG), insulin resistance index (IRI), insulin sensitivity index (ISI) and 30 min net increment of insulin/30min net increment of glucose (AI 30 /AG 30 ) were examined in 44 individuals with NGT, 45 subjects with impaired glucose tolerance (IGT), 66 recently diagnosed diabetics and 175 well-established diabetics. Results: The insulin resistance index (IRI) increased progressively from that in NGT individuals to that in recently diabetics (20 ± 1. 5→3.1 ± 1.6→4.1 ± 1.8), while the 2hIns/2hPG, ΔI 30 /ΔG 30 and ISI decreased progressively with significant differences between those in successive groups (P 30 /ΔG 30 and ISI kept decreasing (values in patients with disease history less than 3 yrs vs those in patients with disease over 3yrs: 2.9 ± 3.2 vs 2.4 + 2.3, 30.2 + 1.1 vs 23.4 ± 2.3, P 30 /ΔG 30 were significantly correlated with ISI (F =96.3, 58.4 and 47.5 respectively). For principal component analysis display, the cumulative contribution rate of four parameters (2hIns/2hPG, ISI, ΔI 30 /ΔG 30 and 2h C-peptide) exceeded 85% (86.5%). Conclusion: As the dysfunction of glucose metabolism proceeded from IGT to well established diabetes, the IR increased first with decrease of β-cell secretion followed. The parameters 2hIns/2hPG, ISI, 2h C-peptide ΔI 30 /ΔG 30 were especially useful for the investigation . (authors)

  1. [Effect of renshen jianxin capsule for alleviating insulin resistance in patients with coronary heart disease and glucose tolerance impairment].

    Science.gov (United States)

    Li, Ai-Min; Zhao, Jia

    2009-09-01

    To explore the effect of Renshen Jianxin Capsule (RJC) on insulin resistance in patients with coronary heart disease (CHD) and glucose tolerance impairment (GTI). Eighty patients with CHD-GTI of qi-deficiency blood-stasis syndrome were randomly assigned to 2 groups equally, the treated group was treated by RJC and the control group by metformin, based on the conventional Western medical treatment with nitric esters for 20 weeks. Changes before and after treatment in clinical symptoms and levels of blood glucose insulin, and insulin sensitivity index (ISI) were observed. The scores of clinical symptoms of Chinese medicine decreased in both groups, which showed statistical significances compared with those before treatment (P 0.05). RJC was effective in improving insulin resistant, which may be one of the mechanisms of its therapeutic effect on CHD.

  2. Nilotinib versus dasatinib as second-line therapy in patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase who are resistant or intolerant to imatinib: a cost-effectiveness analysis based on real-world data.

    Science.gov (United States)

    Li, Nanxin; Yang, Xi; Fan, Liangyi; Totev, Todor; Guerin, Annie; Chen, Lei; Bhattacharyya, Subrata; Joseph, George

    2017-04-01

    To evaluate the cost-effectiveness of second-line nilotinib vs dasatinib among patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) who are resistant or intolerant to imatinib, from a US third-party perspective. A lifetime partitioned survival model was developed to compare the costs and effectiveness of nilotinib vs dasatinib, which included four health states: CP on treatment, CP post-discontinuation, progressive disease (accelerated phase [AP] or blast crisis [BC]), and death. Time on treatment, progression-free survival, and overall survival of nilotinib and dasatinib were estimated using real-world comparative effectiveness data. Parametric survival models were used to extrapolate outcomes beyond the study period. Drug treatment costs, medical costs, and adverse event costs were obtained from the literature and publicly available databases. Utilities of health states were derived from the literature. Incremental cost-effectiveness ratios, including incremental cost per life-year (LY) gained and incremental cost per quality-adjusted life-year (QALY) gained, were estimated comparing nilotinib and dasatinib. Deterministic sensitivity analyses were performed by varying patient characteristics, cost, and utility inputs. Over a lifetime horizon, nilotinib-treated patients were associated with 11.7 LYs, 9.1 QALYs, and a total cost of $1,409,466, while dasatinib-treated patients were associated with 9.5 LYs, 7.3 QALYs, and a total cost of $1,422,122. In comparison with dasatinib, nilotinib was associated with better health outcomes (by 2.2 LYs and 1.9 QALYs) and lower total costs (by $12,655). Deterministic sensitivity analysis results showed consistent findings in most scenarios. In the absence of long-term real-world data, the lifetime projection could not be validated. Compared with dasatinib, second-line nilotinib was associated with better life expectancy, better quality-of-life, and lower costs among patients

  3. Saccharin Increases Fasting Blood Glucose but Not Liver Insulin Resistance in Comparison to a High Fructose-Fed Rat Model

    Directory of Open Access Journals (Sweden)

    Avshalom Leibowitz

    2018-03-01

    Full Text Available Recent data indicate that artificial sweeteners (AS may have deleterious effects on glucose metabolism. The purpose of this study was to compare the effects of AS and the effects of a high fructose diet (HFrD on glucose metabolism and insulin resistance (IR in Sprague-Dawley (SD rats. SD rats were fed either regular chow, chow with saccharin (Sac (0.1 mg/mL placed in their water, or HFrD for seven weeks. Glucose, insulin, and triglycerides (Tg levels were measured upon completion. A homeostatic model assessment (HOMA-IR index was used to determine insulin resistance. The liver was stained to detect signs of a fatty liver. Hepatic mRNA expression of glucose metabolism regulation genes, Srepb-1c (sterol regulatory element binding protein and ChREB (α & β (carbohydrate response element binding protein, as well as other glycolytic and lipogenic genes including glucose-6-phosphatase (G6pc, were considered IR markers. Both HFrD and Sac significantly increased fasting blood glucose levels compare to the control (140 ± 5 and 137 ± 6 vs. 118 ± 3 mg/dL, respectively, p < 0.05. However, only HFrD increased insulin secretion (0.99 ± 0.12 vs. 0.7 ± 0.1 and 0.6 ± 0.1 ug/L, Tg levels (420 ± 43 vs. 152 ± 20 and 127 ± 13 mg/dL, and the HOMA-IR index (3.4 ± 0.4 vs. 2.3 ± 0.36 and 2.13 ± 0.3 (HFrD vs. control and sac, p < 0.05. Fatty liver changes were only observed in HFrD fed rats. The expression of ChREB β, Srepb-1c, and G6pc mRNA were only significantly elevated (between 2–10 times folds, p < 0.05 in HFrD fed rats. Sac may increase fasting blood glucose but has no effect on liver insulin resistance.

  4. S961, an insulin receptor antagonist causes hyperinsulinemia, insulin-resistance and depletion of energy stores in rats

    Energy Technology Data Exchange (ETDEWEB)

    Vikram, Ajit [Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), SAS Nagar, Mohali, Punjab 160 062 (India); Jena, Gopabandhu, E-mail: gbjena@gmail.com [Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), SAS Nagar, Mohali, Punjab 160 062 (India)

    2010-07-23

    Research highlights: {yields}Insulin receptor antagonist S961 causes hyperglycemia, hyperinsulinemia and insulin resistance in rats. {yields}Peroxysome-proliferator-activated-receptor-gamma agonist pioglitazone improves S961 induced hyperglycemia and glucose intolerance. {yields}Long term treatment with insulin receptor antagonist S961 results in the decreased adiposity and hepatic glycogen content. {yields}Improvement in the hyperglycemia and glucose intolerance by pioglitazone clearly demonstrates that S961 treated rats can be successfully used to screen the novel therapeutic interventions having potential to improve glucose disposal through receptor independent mechanisms. -- Abstract: Impairment in the insulin receptor signaling and insulin mediated effects are the key features of type 2 diabetes. Here we report that S961, a peptide insulin receptor antagonist induces hyperglycemia, hyperinsulinemia ({approx}18-fold), glucose intolerance and impairment in the insulin mediated glucose disposal in the Sprague-Dawley rats. Further, long-term S961 treatment (15 day, 10 nM/kg/day) depletes energy storage as evident from decrease in the adiposity and hepatic glycogen content. However, peroxysome-proliferator-activated-receptor-gamma (PPAR{gamma}) agonist pioglitazone significantly (P < 0.001) restored S961 induced hyperglycemia (196.73 {+-} 16.32 vs. 126.37 {+-} 27.07 mg/dl) and glucose intolerance ({approx}78%). Improvement in the hyperglycemia and glucose intolerance by pioglitazone clearly demonstrates that S961 treated rats can be successfully used to screen the novel therapeutic interventions having potential to improve glucose disposal through receptor independent mechanisms. Further, results of the present study reconfirms and provide direct evidence to the crucial role of insulin receptor signaling in the glucose homeostasis and fuel metabolism.

  5. S961, an insulin receptor antagonist causes hyperinsulinemia, insulin-resistance and depletion of energy stores in rats

    International Nuclear Information System (INIS)

    Vikram, Ajit; Jena, Gopabandhu

    2010-01-01

    Research highlights: →Insulin receptor antagonist S961 causes hyperglycemia, hyperinsulinemia and insulin resistance in rats. →Peroxysome-proliferator-activated-receptor-gamma agonist pioglitazone improves S961 induced hyperglycemia and glucose intolerance. →Long term treatment with insulin receptor antagonist S961 results in the decreased adiposity and hepatic glycogen content. →Improvement in the hyperglycemia and glucose intolerance by pioglitazone clearly demonstrates that S961 treated rats can be successfully used to screen the novel therapeutic interventions having potential to improve glucose disposal through receptor independent mechanisms. -- Abstract: Impairment in the insulin receptor signaling and insulin mediated effects are the key features of type 2 diabetes. Here we report that S961, a peptide insulin receptor antagonist induces hyperglycemia, hyperinsulinemia (∼18-fold), glucose intolerance and impairment in the insulin mediated glucose disposal in the Sprague-Dawley rats. Further, long-term S961 treatment (15 day, 10 nM/kg/day) depletes energy storage as evident from decrease in the adiposity and hepatic glycogen content. However, peroxysome-proliferator-activated-receptor-gamma (PPARγ) agonist pioglitazone significantly (P < 0.001) restored S961 induced hyperglycemia (196.73 ± 16.32 vs. 126.37 ± 27.07 mg/dl) and glucose intolerance (∼78%). Improvement in the hyperglycemia and glucose intolerance by pioglitazone clearly demonstrates that S961 treated rats can be successfully used to screen the novel therapeutic interventions having potential to improve glucose disposal through receptor independent mechanisms. Further, results of the present study reconfirms and provide direct evidence to the crucial role of insulin receptor signaling in the glucose homeostasis and fuel metabolism.

  6. Prevalence of Food Additive Intolerance

    DEFF Research Database (Denmark)

    Madsen, Charlotte Bernhard

    1994-01-01

    1 The existing prevalence estimates of food additive intolerance(1-4) are being reviewed. 2 In the EEC report the estimated frequency of food additive intolerance is 0.03% to 0.15% based on data from patient groups. 3 The British population study results in a prevalence estimate of 0...... The prevalence estimates vary with a factor 100. As the results vary so do the study populations. 6 If the different study populations are accounted for, a common conclusion can be drawn: Food additive intolerance is found in adults with atopic symptoms from the respiratory tract and skin. The prevalence...... estimates are questionable but may be less than 0.15%. In adults and children with reproducible, and with more subjective symptoms, such as headache and behavioural/mood change the prevalence is even lower (0.026%). Food additive intolerance is primarily found in atopic children with cutaneous symptoms...

  7. Effect of cholecalciferol and levo carnitine on plasma glucose, plasma insulin and insulin resistance in type 2 diabetic rats

    International Nuclear Information System (INIS)

    Anwar, M. K.; Hussain, M. M.; Khan, M. A.; Ahmad, T.

    2013-01-01

    Objective: To compare the effects of combined and individual supplementation of cholecalciferol and levo carnitine on plasma glucose, plasma insulin and insulin resistance in type 2 diabetic rats. Methods: The randomised controlled trial was conducted at the Department of Physiology, Army Medical College, Rawalpindi, between October 2010 and April 2011. It comprised 80 healthy Sprague Dawley rats who were divided into four groups (n = 20 each). Rats were fed high-fat diet for 2 weeks followed by an intraperitoneal injection of streptozocin to induce type 2 diabetes mellitus. Group I served as diabetic control; group II was given cholecalciferol; group III; levo carnitine; and group IV was administered cholecalciferol and levo carnitine together. After 6 days of supplementation, terminal intracardiac blood extraction was done and samples were analysed for fasting plasma glucose and plasma insulin. Insulin resistance was calculated by homeostatic model assessment for insulin resistance. SPSS 17.0 was used for statistical analysis. Results: Fasting plasma glucose levels were significantly decreased (p <0.001) in the combined supplementation group compared to the diabetic control and individual supplementation groups. Combined supplementation showed a significant increase in fasting plasma insulin levels when compared with diabetic control and levo carnitine groups (p <0.001), and the effect of combined supplementation on ameliorating insulin resistance was significantly better (p <0.001) as compared to the individual supplementation of cholecalciferol and levo carnitine. Conclusions: The combined supplementation of cholecalciferol and levo carnitine for 6 days markedly improved the glycaemic control, insulin secretion and insulin resistance in type 2 diabetic rats on high-fat diet. A prolonged supplementation by both the compounds along with caloric restriction may yield a more promising outcome. (author)

  8. Reduced glucose tolerance and insulin resistance induced by steroid treatment, relative physical inactivity, and high-calorie diet impairs the incretin effect in healthy subjects

    DEFF Research Database (Denmark)

    Hansen, K B; Vilsbøll, T; Bagger, J I

    2010-01-01

    The loss of incretin effect in patients with type 2 diabetes mellitus may be secondary to impaired glucose homeostasis. We investigated whether reduced glucose tolerance and insulin resistance induced by steroid treatment, relative physical inactivity, and high-calorie diet in healthy young males...

  9. Correlation of blood glucose, serum chemerin and insulin resistance with NAFLD in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Zhang, Zhengjun; Wang, Jijun; Wang, Hongmei

    2018-03-01

    Non-alcoholic fatty liver disease (NAFLD) is a form of clinical syndrome characterized by the fatty degeneration in liver histology and should be further investigated. The aim of the study was to investigate the effects of blood glucose, serum chemerin and insulin resistance on non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus to provide a basis for the prevention and treatment thereof. In total, 300 patients with type 2 diabetes mellitus treated and admitted into the Endocrinology Department of our hospital from June 2015 to June 2017 were enrolled and divided into the simple type 2 diabetes mellitus (group A) and concurrent NAFLD (group B) groups. The sex, age, body mass index (BMI), blood pressure, blood biochemical indexes and chemerin level were compared between the two groups. The patients in group B were further divided into the mild fatty liver (group B1), moderate fatty liver (group B2) and severe fatty liver (group B3) groups. The sex, age, BMI blood pressure, blood biochemical indexes and chemerin level were also compared among the three groups. Finally, the risk factors of type 2 diabetes mellitus complicated by NAFLD were analyzed via logistic regression. The BMI, fasting plasma glucose (FPG), 2 h post-prandial plasma glucose (2hPG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), alanine aminotransferase (ALT), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR) and HOMA-β indexes and serum chemerin level in group B were significantly higher than those in group A (Ptype 2 diabetes mellitus complicated by NAFLD is closely associated with severe glucose-lipid metabolism disorder and insulin resistance, and BMI, FPG, TC, LDL-c, FINS, HOMA-IR and chemerin constitute risk factors of concurrent NAFLD.

  10. In vivo assessment of cardiac insulin resistance by nuclear probes using an iodinated tracer of glucose transport

    International Nuclear Information System (INIS)

    Briat, Arnaud; Slimani, Lotfi; Perret, Pascale; Villemain, Daniele; Fagret, Daniel; Ghezzi, Catherine; Halimi, Serge; Demongeot, Jacques

    2007-01-01

    Insulin resistance, implying depressed cellular sensitivity to insulin, is a risk factor for type 2 diabetes and cardiovascular disease. This study is the first step towards the development of a technique of insulin resistance measurement in humans with a new tracer of glucose transport, [ 123 I]6-deoxy-6-iodo-D-glucose (6DIG). We investigated 6DIG kinetics in anaesthetised control rats and in three models of insulin-resistant rats: fructose fed, Zucker and ZDF. The study of myocardial 6DIG activity was performed under two conditions: first, 6DIG was injected under the baseline condition and then it was injected after a bolus injection of insulin. After each injection, radioactivity was measured over 45 min by external detection via NaI probes, in the heart and blood. A tri-compartment model was developed to obtain fractional transfer coefficients of 6DIG from the blood to the heart. These coefficients were significantly increased with insulin in control rats and did not change significantly in insulin-resistant rats. The ratio of the coefficient obtained under insulin to that obtained under basal conditions gave an index of cardiac insulin resistance for each animal. The mean values of these ratios were significantly lower in insulin-resistant than in control rats: 1.16 ± 0.06 vs 2.28 ± 0.18 (p < 0.001) for the fructose-fed group, 0.92 ± 0.05 vs 1.62 ± 0.25 (p < 0.01) for the Zucker group and 1.34 ± 0.06 vs 2.01 ± 0.26 (p < 0.05) for the ZDF group. These results show that 6DIG could be a useful tracer to image cardiac insulin resistance. (orig.)

  11. In vivo assessment of cardiac insulin resistance by nuclear probes using an iodinated tracer of glucose transport

    Energy Technology Data Exchange (ETDEWEB)

    Briat, Arnaud; Slimani, Lotfi; Perret, Pascale; Villemain, Daniele; Fagret, Daniel; Ghezzi, Catherine [INSERM, E0340, Radiopharmaceutiques Biocliniques, Grenoble (France); Univ Grenoble, Grenoble (France); Halimi, Serge [Univ Grenoble, Grenoble (France); Hopital Michallon, Service de Diabetologie, CHRU Grenoble, Grenoble (France); Demongeot, Jacques [Univ Grenoble, Grenoble (France); CNRS, UMR 5525, Grenoble (France)

    2007-11-15

    Insulin resistance, implying depressed cellular sensitivity to insulin, is a risk factor for type 2 diabetes and cardiovascular disease. This study is the first step towards the development of a technique of insulin resistance measurement in humans with a new tracer of glucose transport, [{sup 123}I]6-deoxy-6-iodo-D-glucose (6DIG). We investigated 6DIG kinetics in anaesthetised control rats and in three models of insulin-resistant rats: fructose fed, Zucker and ZDF. The study of myocardial 6DIG activity was performed under two conditions: first, 6DIG was injected under the baseline condition and then it was injected after a bolus injection of insulin. After each injection, radioactivity was measured over 45 min by external detection via NaI probes, in the heart and blood. A tri-compartment model was developed to obtain fractional transfer coefficients of 6DIG from the blood to the heart. These coefficients were significantly increased with insulin in control rats and did not change significantly in insulin-resistant rats. The ratio of the coefficient obtained under insulin to that obtained under basal conditions gave an index of cardiac insulin resistance for each animal. The mean values of these ratios were significantly lower in insulin-resistant than in control rats: 1.16 {+-} 0.06 vs 2.28 {+-} 0.18 (p < 0.001) for the fructose-fed group, 0.92 {+-} 0.05 vs 1.62 {+-} 0.25 (p < 0.01) for the Zucker group and 1.34 {+-} 0.06 vs 2.01 {+-} 0.26 (p < 0.05) for the ZDF group. These results show that 6DIG could be a useful tracer to image cardiac insulin resistance. (orig.)

  12. Rosiglitazone treatment of patients with extreme insulin resistance and diabetes mellitus due to insulin receptor mutations has no effects on glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Vestergaard, H; Lund, S; Pedersen, O

    2001-01-01

    Rosiglitazone, a thiazolidinedione (TZD), increases insulin sensitivity by reducing levels of plasma NEFA, triglycerides (TG), glucose and serum insulin. Rosiglitazone treatment decreases insulin resistance in type 2 diabetic patients, but no data exist concerning rosiglitazone treatment of patie......Rosiglitazone, a thiazolidinedione (TZD), increases insulin sensitivity by reducing levels of plasma NEFA, triglycerides (TG), glucose and serum insulin. Rosiglitazone treatment decreases insulin resistance in type 2 diabetic patients, but no data exist concerning rosiglitazone treatment...

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    This study investigated whether undernutrition (UN) during late fetal life can programme the subsequent adult life adaptation of glucose homeostasis and metabolism during pregnancy and lactation. Twenty-four primiparous experimental ewes were used. Twelve had been exposed to a prenatal NORM level...... during lactation. There was no effect of prenatal UN on glucose tolerance during G-IGTT, however, during RG-IGTT LOW was more glucose intolerant and apparently more insulin resistant compared to NORM. In conclusion, UN during late fetal life in sheep impairs subsequent pancreatic insulin secretory...

  14. The role of colonic microbiota in lactose intolerance

    NARCIS (Netherlands)

    Zhong, Y; Priebe, M. G.; Vonk, R. J.; Huang, CY; Antoine, JM; He, T; Harmsen, HJM; Welling, GW

    In a previous study we observed a clear difference in lactose intolerance symptoms after a 25-g lactose load in two groups of persons with lactase nonpersistence and similar small intestinal lactase activity. From this observation we hypothesized a colon resistance factor. To identify this factor,

  15. Chronic reactive oxygen species exposure inhibits glucose uptake and causes insulin resistance in C2C12 myotubes.

    Science.gov (United States)

    Ding, Hongwen; Heng, Baoli; He, Wenfang; Shi, Liping; Lai, Caiyong; Xiao, Long; Ren, Haolin; Mo, Shijie; Su, Zexuan

    2016-09-16

    Reactive oxygen species (ROS) is an important regulator in cellular signaling transduction, and many previous studies have indicated that acute ROS stimulation improves insulin sensitivity in skeletal muscle. In the study, we found that chronic ROS treatment caused serious insulin resistance in C2C12 myotubes. Glucose uptake and consumption assay indicated that pretreatment with 80 μM H2O2 for 2 h inhibited insulin-stimulated glucose uptake in C2C12 myotubes, and the reason for it, is that chronic H2O2 treatment decreased insulin-induced glucose transporter 4 (GLUT4) translocation from cell plasma to cell membrane. Moreover, Akt2 phosphorylation depended on insulin was reduced in C2C12 myotubes of chronic H2O2 treatment. Together, this study provides further demonstration that chronic ROS stress is associated with insulin resistance of skeletal muscle in the progression of type 2 diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Chow fed UC Davis strain female Lepr fatty Zucker rats exhibit mild glucose intolerance, hypertriglyceridemia, and increased urine volume, all reduced by a Brown Norway strain chromosome 1 congenic donor region.

    Directory of Open Access Journals (Sweden)

    Craig H Warden

    Full Text Available Our objective is to identify genes that influence the development of any phenotypes of type 2 diabetes (T2D or kidney disease in obese animals. We use the reproductively isolated UC Davis fatty Zucker strain rat model in which the defective chromosome 4 leptin receptor (LeprfaSte/faSte results in fatty obesity. We previously produced a congenic strain with the distal half of chromosome 1 from the Brown Norway strain (BN on a Zucker (ZUC background (BN.ZUC-D1Rat183-D1Rat90. Previously published studies in males showed that the BN congenic donor region protects from some phenotypes of renal dysfunction and T2D. We now expand our studies to include females and expand phenotyping to gene expression. We performed diabetes and kidney disease phenotyping in chow-fed females of the BN.ZUC-D1Rat183-D1Rat90 congenic strain to determine the specific characteristics of the UC Davis model. Fatty LeprfaSte/faSte animals of both BN and ZUC genotype in the congenic donor region had prediabetic levels of fasting blood glucose and blood glucose 2 hours after a glucose tolerance test. We observed significant congenic strain chromosome 1 genotype effects of the BN donor region in fatty females that resulted in decreased food intake, urine volume, glucose area under the curve during glucose tolerance test, plasma triglyceride levels, and urine glucose excretion per day. In fatty females, there were significant congenic strain BN genotype effects on non-fasted plasma urea nitrogen, triglyceride, and creatinine. Congenic region genotype effects were observed by quantitative PCR of mRNA from the kidney for six genes, all located in the chromosome 1 BN donor region, with potential effects on T2D or kidney function. The results are consistent with the hypothesis that the BN genotype chromosome 1 congenic region influences traits of both type 2 diabetes and kidney function in fatty UC Davis ZUC females and that there are many positional candidate genes.

  17. Lifelong Physical Activity Prevents Aging-Associated Insulin Resistance in Human Skeletal Muscle Myotubes via Increased Glucose Transporter Expression

    DEFF Research Database (Denmark)

    Bunprajun, Tipwadee; Henriksen, Tora Ida; Scheele, Camilla

    2013-01-01

    Both aging and physical inactivity are associated with increased development of insulin resistance whereas physical activity has been shown to promote increased insulin sensitivity. Here we investigated the effects of physical activity level on aging-associated insulin resistance in myotubes......, and significantly higher GLUT4 protein. It is likely that physical activity induces a number of stable adaptations, including increased GLUT4 expression that are retained in cells ex vivo and protect, or delay the onset of middle-aged-associated insulin resistance. Additionally, a sedentary lifestyle has an impact...... chain protein expression. Interestingly MHCIIa was increased only in myotubes from middle-aged active individuals. Middle-aged sedentary cells had intact insulin-stimulated Akt phosphorylation however, the same cell showed ablated insulin-stimulated glucose uptake and GLUT4 translocation to the plasma...

  18. Comparison of the effects on insulin resistance and glucose tolerance of 6-mo high-monounsaturated-fat, low-fat, and control diets

    DEFF Research Database (Denmark)

    Due, Anette; Larsen, Thomas M; Hermansen, Kjeld

    2008-01-01

    and after the 6-mo dietary intervention. All foods were provided by a purpose-built supermarket. RESULTS: After 6 mo, the MUFA diet reduced fasting glucose (-3.0%), insulin (-9.4%), and the homeostasis model assessment of insulin resistance score (-12.1%). Compared with the MUFA diet, the control diet......BACKGROUND: The effect of dietary fat and carbohydrate on glucose metabolism has been debated for decades. OBJECTIVE: The objective was to compare the effect of 3 ad libitum diets, different in type and amount of fat and carbohydrate, on insulin resistance and glucose tolerance subsequent to weight...

  19. Effect of Arctium Lappa Root Extract on Glucose Levels and Insulin Resistance in Rats with High Sucrose Diet

    Directory of Open Access Journals (Sweden)

    A Ahangarpour

    2013-06-01

    Full Text Available Introduction: Diabetes Mellitus is a growing health problem in all over the world. Arctium Lappa has been used therapeutically in Europe, North America and Asia. Antioxidants and antidiabetic compounds have been found in the root of Arctium Lappa. This study intends to investigate the effects of Arctium Lappa root aqueous extract on glucose, insulin levels and Fasting Insulin Resistance Index in female rats with high sucrose diet. Methods: 40 female Wistar rats weighting 150-250(g were applied. After having a diet induced by sucrose 50% in drinking water for 5 weeks, the animals were randomly divided into two groups of control, sucrose induced, and three groups of sucrose induced along with Arctium Lappa root aqueous extract (50,100,200 mg/Kg (8 rats in each group. Treatment by extracts was used during 2 weeks (i.p. and 24 hours after the last treatment, heart blood samples were gathered. After Blood samples were centrifuged, fasting plasma glucose (12 h was determined by kit and fasting insulin concentration was assayed by Enzyme-linked immunosorbent assay (Elisa methods. Result: Glucose levels, insulin and FIRI in sucrose group significantly increased in comparison with control group. Glucose levels in aqueous extract groups; 50 mg/kg (116.14±16.64mg/dl and 200 mg/kg (90.66±22.58 mg/dl in comparison with sucrose group (140.5±18.73 mg/dl significantly decreased. Insulin level and FIRI in all of aqueous extract groups were significantly decreased (P<0.001 in comparison with sucrose group. Conclusions: Arctium Lappa root aqueous extracts in animal model has revealed significant decrease in blood glucose and insulin levels.

  20. Glucose effectiveness in nondiabetic relatives

    DEFF Research Database (Denmark)

    Egede, M B; Henriksen, J-E; Durck, T T

    2014-01-01

    AIMS: Reduced glucose effectiveness is a predictor of future glucose tolerance in individuals with a family history of type 2 diabetes. We examined retrospectively at 10 years in normoglycemic relatives of diabetic subjects (RELs) the pathophysiological role of glucose effectiveness...... in the development of isolated impaired fasting glucose, glucose intolerance, and acute insulin release. METHODS: At 0 years, 19 RELs and 18 matched control subjects had glucose effectiveness (GE), insulin sensitivity, acute insulin release (AIR)IVGTT, and disposition index measured during an iv glucose tolerance...... test (IVGTT), using the minimal model analysis. At 0 and 10 years, oral glucose tolerance (OGTT) and AIROGTT were determined. RESULTS: At 0 years, fasting glucose (FG) and GE were raised in RELs, but insulin sensitivity and AIROGTT were reduced (P ≤ .05) compared with controls. At 10 years, RELs...

  1. Angiotensin receptor blockade improves cardiac mitochondrial activity in response to an acute glucose load in obese insulin resistant rats

    Directory of Open Access Journals (Sweden)

    Max Thorwald

    2018-04-01

    Full Text Available Hyperglycemia increases the risk of oxidant overproduction in the heart through activation of a multitude of pathways. Oxidation of mitochondrial enzymes may impair their function resulting in accumulation of intermediates and reverse electron transfer, contributing to mitochondrial dysfunction. Furthermore, the renin-angiotensin system (RAS becomes inappropriately activated during metabolic syndrome, increasing oxidant production. To combat excess oxidant production, the transcription factor, nuclear factor erythriod-2- related factor 2 (Nrf2, induces expression of many antioxidant genes. We hypothesized that angiotensin II receptor type 1 (AT1 blockade improves mitochondrial function in response to an acute glucose load via upregulation of Nrf2. To address this hypothesis, an oral glucose challenge was performed in three groups prior to dissection (n = 5–8 animals/group/time point of adult male rats: 1 Long Evans Tokushima Otsuka (LETO; lean strain-control, 2 insulin resistant, obese Otsuka Long Evans Tokushima Fatty (OLETF, and 3 OLETF + angiotensin receptor blocker (ARB; 10 mg olmesartan/kg/d × 6 weeks. Hearts were collected at T0, T60, and T120 minutes post-glucose infusion. ARB increased Nrf2 binding 32% compared to OLETF at T60. Total superoxide dismutase (SOD and catalase (CAT activities were increased 45% and 66% respectively in ARB treated animals compared to OLETF. Mitochondrial enzyme activities of aconitase, complex I, and complex II increased by 135%, 33% and 66%, respectively in ARB compared to OLETF. These data demonstrate the protective effects of AT1 blockade on mitochondrial function during the manifestation of insulin resistance suggesting that the inappropriate activation of AT1 during insulin resistance may impair Nrf2 translocation and subsequent antioxidant activities and mitochondrial function. Keywords: Angiotensin II, Mitochondria, Cardiac, Antioxidant enzymes, TCA cycle

  2. Assessing the test–retest repeatability of insulin resistance measures: Homeostasis model assessment 2 and oral glucose insulin sensitivity

    Directory of Open Access Journals (Sweden)

    Catherine A.P. Crofts

    2017-10-01

    Full Text Available Background: Insulin resistance is commonly assessed using the homeostasis model assessment (HOMA variants. HOMA is potentially insensitive to change because of its high coefficient of variation. The repeatability coefficient is an alternative means of assessing test repeatability. To be confident of clinical change, rather than biological variation, a subsequent test needs to differ from the former by more than the repeatability coefficient using the equation. Test 1 = Test 2 ± repeatability coefficient. The repeatability coefficients for measures of insulin resistance are unknown. Aim: To compare the repeatability coefficient of HOMA2 variants (Beta-cell function [%B], insulin sensitivity [%S], insulin resistance [IR] to a dynamic measure of insulin resistance, and the oral glucose insulin sensitivity (OGIS test. Setting: The raw data from a previously used data set were reanalysed. Methods: Glycaemic and insulinaemic tests were performed on 32 men and women both with (n = 10 and without type 2 diabetes (n = 22. From these data, eight fasting tests and three 50-g oral glucose tolerance tests were used to calculate HOMA2 and OGIS. The methods of Bland and Altman assessed repeatability. Results: Repeatability coefficients for all participants for the HOMA2 %B, %S and IR variants were 72.91, 189.75 and 0.9, which equates to 89%, 135% and 89% of their respective grand means. By contrast, OGIS had a repeatability coefficient of 87.13, which equates to 21% of the grand mean. Conclusion: Because of the high repeatability coefficient relative to the grand mean, use of HOMA2 measures for assessing insulin resistance in small population studies should be reconsidered.

  3. Insulin resistance according to β-cell function in women with polycystic ovary syndrome and normal glucose tolerance.

    Directory of Open Access Journals (Sweden)

    Do Kyeong Song

    Full Text Available Polycystic ovary syndrome (PCOS is associated with insulin resistance (IR and compensatory hyperinsulinemia. IR is recognized as a major risk factor for the development of type 2 diabetes mellitus. However, few studies have investigated IR in women with PCOS and normal glucose tolerance. The objective of this study was to evaluate IR and β-cell function in women with PCOS and normal glucose tolerance. Additionally, we sought to evaluate the usefulness of oral glucose tolerance test (OGTT-derived IR indices in lean women with PCOS.We recruited 100 women with PCOS and normal glucose tolerance and 100 age- and BMI-matched women as controls. IR and insulin secretory indices, including the homeostasis-model assessment (HOMA-IR, HOMA-M120, HOMA-F and the Stumvoll index, were calculated from an OGTT. Increased β-cell function was defined as>75th percentile for the HOMA-F in control women.Women with PCOS had higher values for post-load 2-hour glucose, fasting insulin, post-load 2-hour insulin, HOMA-IR, HOMA-M120, HOMA-F and lower values for the Stumvoll index than the controls (all Ps<0.05. Women with PCOS and increased β-cell function showed lower Stumvoll index values than the matched controls (P<0.05. The HOMA-F was significantly associated with the HOMA-M120 and Stumvoll index when adjusted for age and BMI in a multiple regression analysis (all Ps<0.05. The HOMA-M120 was positively correlated with triglycerides and free testosterone, and the Stumvoll index was negatively correlated with triglycerides and free testosterone in lean women with PCOS (all Ps<0.05.Women with PCOS and normal glucose tolerance showed higher IR than controls matched for age, BMI, and β-cell function. β-cell function was increased in women with PCOS when compared to the matched controls, but not when the lean subjects were compared to the matched controls separately. Therefore, early evaluation of IR in women with PCOS and normal glucose tolerance may be needed.

  4. Lactobacillus sakei OK67 ameliorates high-fat diet-induced blood glucose intolerance and obesity in mice by inhibiting gut microbiota lipopolysaccharide production and inducing colon tight junction protein expression.

    Science.gov (United States)

    Lim, Su-Min; Jeong, Jin-Ju; Woo, Kyung Hee; Han, Myung Joo; Kim, Dong-Hyun

    2016-04-01

    A high-fat diet (HFD) induces obesity and the associated increases in blood glucose and inflammation through changes in gut microbiota, endotoxemia, and increased gut permeability. To counteract this, researchers have suggested that the use of probiotics that suppress production of proinflammatory lipopolysaccharide (LPS). Here, we tested whether Lactobacillus sakei OK67, which inhibits gut microbiota LPS production selected from among the lactic acid bacteria isolated from kimchi, exerted antihypoglycemic or anti-inflammatory effects in HFD-fed mice. Mice were randomly divided into 2 groups and fed an HFD or a low-fat diet for 4 weeks. These groups were further subdivided; 1 subgroup was treated with L sakei OK67 and fed the experimental diet for 4.5 weeks, whereas the other subgroup was fed the experimental diet alone. L sakei OK67 treatment lowered HFD-elevated LPS levels in blood and colonic fluid and significantly decreased HFD-elevated fasting blood glucose levels and the area under the curve in an oral glucose tolerance test. L sakei OK67 treatment inhibited HFD-induced body and epididymal fat weight gains, suppressed HFD-induced tumor necrosis factor-α and interleukin-1β expression and nuclear factor-κB activation in the colon, and significantly increased HFD-suppressed interleukin-10 and tight junction protein expression in the colon. Oral administration of L sakei OK67 significantly downregulated HFD-induced expression of peroxisome proliferator-activated receptor γ, fatty acid synthase, and tumor necrosis factor-α in adipose tissue. In addition, L sakei OK67 treatment strongly inhibited nuclear factor-κB activation in LPS-stimulated peritoneal macrophages. We report that L sakei OK67 ameliorates HFD-induced hyperglycemia and obesity by reducing inflammation and increasing the expression of colon tight junction proteins in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Prevalence of Food Additive Intolerance

    DEFF Research Database (Denmark)

    Madsen, Charlotte Bernhard

    1994-01-01

    estimates are questionable but may be less than 0.15%. In adults and children with reproducible, and with more subjective symptoms, such as headache and behavioural/mood change the prevalence is even lower (0.026%). Food additive intolerance is primarily found in atopic children with cutaneous symptoms......1 The existing prevalence estimates of food additive intolerance(1-4) are being reviewed. 2 In the EEC report the estimated frequency of food additive intolerance is 0.03% to 0.15% based on data from patient groups. 3 The British population study results in a prevalence estimate of 0.......026%. The challenged population is 81 children and adults with a history of reproducible clinical symptoms after ingestion of food additives. 4 In the Danish population study a prevalence of 1-2% is found in children age 5-16. In this study a total of 606 children mainly with atopic disease have been challenged. 5...

  6. The UDP-glucose ceramide glycosyltransferase (UGCG) and the link to multidrug resistance protein 1 (MDR1).

    Science.gov (United States)

    Wegner, Marthe-Susanna; Gruber, Lisa; Mattjus, Peter; Geisslinger, Gerd; Grösch, Sabine

    2018-02-06

    The UDP-glucose ceramide glycosyltransferase (UGCG) is a key enzyme in the sphingolipid metabolism by generating glucosylceramide (GlcCer), the precursor for all glycosphingolipids (GSL), which are essential for proper cell function. Interestingly, the UGCG is also overexpressed in several cancer types and correlates with multidrug resistance protein 1 (MDR1) gene expression. This membrane protein is responsible for efflux of toxic substances and protects cancer cells from cell damage through chemotherapeutic agents. Studies showed a connection between UGCG and MDR1 overexpression and multidrug resistance development, but the precise underlying mechanisms are unknown. Here, we give an overview about the UGCG and its connection to MDR1 in multidrug resistant cells. Furthermore, we focus on UGCG transcriptional regulation, the impact of UGCG on cellular signaling pathways and the effect of UGCG and MDR1 on the lipid composition of membranes and how this could influence multidrug resistance development. To our knowledge, this is the first review presenting an overview about UGCG with focus on the relationship to MDR1 in the process of multidrug resistance development.

  7. A simple way to identify insulin resistance in non-diabetic acute coronary syndrome patients with impaired fasting glucose

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    Sayantan Ray

    2012-01-01

    Full Text Available Background and Objective: The incidence of coronary artery disease (CAD is increasing in India. Recent data suggesting insulin resistance can predict cardiovascular disease independently of the other risk factors, such as hypertension, visceral obesity, or dyslipidemia, so a focus on the relation between acute coronary syndrome (ACS and insulin resistance is relevant. Several studies addressing serum lipoprotein ratios as surrogates for insulin resistance have found promising results. We analyzed the association of lipoprotein ratios with the homeostatic model assessment of insulin resistance (HOMA-IR. Methods: One hundred non-diabetic patients with impaired fasting glucose admitted with a diagnosis of ACS were included in the study. Admission fasting glucose and insulin concentrations were measured. The HOMA-IR was used to calculate insulin resistance. The fasting serum total cholesterol (TC, triglycerides (TG, and high-density lipoprotein (HDL-C levels are used to calculate following lipid ratios: TC/HDL-C and TG/HDL-C. The areas under the curves (AUC of the receiver operating characteristic curves (ROC were used to compare the power of these serum lipoprotein ratio markers. Results: Lipoprotein ratios were significantly higher in patients with HOMA Index >2 as compared to patients with Index <2. TG/HDL-C ratio and TC/HDL-C ratio were significantly correlated with HOMA-IR (P < 0.05 as obtained by Pearson′s correlation analysis (r = 0.4459, P = 0.0012; r = 0.4815, P = 0.0004; r = 0.3993; P = 0.0041, respectively. The area under the ROC curve of the TG/HDL-C and TC/HDL-C ratios for predicting insulin resistance was 0.80 (95% CI, 0.67-0.93, 0.78 (95% CI, 0.65-0.91, respectively. Conclusion: A plasma TG/HDL-C ratio and TC/HDL-C ratio provide a simple means of identifying insulin resistant and can be used as the markers of insulin resistance and cardiovascular diseases risk in adult non-diabetic patients.

  8. Tetrahydrobiopterin Has a Glucose-Lowering Effect by Suppressing Hepatic Gluconeogenesis in an Endothelial Nitric Oxide Synthase–Dependent Manner in Diabetic Mice

    Science.gov (United States)

    Abudukadier, Abulizi; Fujita, Yoshihito; Obara, Akio; Ohashi, Akiko; Fukushima, Toru; Sato, Yuichi; Ogura, Masahito; Nakamura, Yasuhiko; Fujimoto, Shimpei; Hosokawa, Masaya; Hasegawa, Hiroyuki; Inagaki, Nobuya

    2013-01-01

    Endothelial nitric oxide synthase (eNOS) dysfunction induces insulin resistance and glucose intolerance. Tetrahydrobiopterin (BH4) is an essential cofactor of eNOS that regulates eNOS activity. In the diabetic state, BH4 is oxidized to 7,8-dihydrobiopterin, which leads to eNOS dysfunction owing to eNOS uncoupling. The current study investigates the effects of BH4 on glucose metabolism and insulin sensitivity in diabetic mice. Single administration of BH4 lowered fasting blood glucose levels in wild-type mice with streptozotocin (STZ)-induced diabetes and alleviated eNOS dysfunction by increasing eNOS dimerization in the liver of these mice. Liver has a critical role in glucose-lowering effects of BH4 through suppression of hepatic gluconeogenesis. BH4 activated AMP kinase (AMPK), and the suppressing effect of BH4 on gluconeogenesis was AMPK-dependent. In addition, the glucose-lowering effect and activation of AMPK by BH4 did not appear in mice with STZ-induced diabetes lacking eNOS. Consecutive administration of BH4 in ob/ob mice ameliorated glucose intolerance and insulin resistance. Taken together, BH4 suppresses hepatic gluconeogenesis in an eNOS-dependent manner, and BH4 has a glucose-lowering effect as well as an insulin-sensitizing effect in diabetic mice. BH4 has potential in the treatment of type 2 diabetes. PMID:23649519

  9. [Abdominal spasms, meteorism, diarrhea: fructose intolerance, lactose intolerance or IBS?].

    Science.gov (United States)

    Litschauer-Poursadrollah, Margaritha; El-Sayad, Sabine; Wantke, Felix; Fellinger, Christina; Jarisch, Reinhart

    2012-12-01

    Meteorism, abdominal spasms, diarrhea, casually obstipation, flatulence and nausea are symptoms of fructose malabsorption (FIT) and/or lactose intolerance (LIT), but are also symptoms of irritable bowel syndrome (IBS). Therefore these diseases should be considered primarily in patients with digestive complaints. For diagnosis an H(2)-breath test is used.In 1,935 patients (526 m, 1,409 f) a fructose intolerance test and in 1,739 patients (518 m,1,221 f) a lactose intolerance test was done.FIT is found more frequently than LIT (57 versus 52 % in adults (p intolerance (HIT). Headache (ca. 10 %), fatigue (ca. 5 %) and dizziness (ca. 3 %) may occur after the test, irrespective whether the test was positive or negative.In more than 2/3 of patients a diet reduced in fructose or lactose may lead to improvement or remission of these metabolic disorders. IBS, which is often correlated with FIT (183/221 patients = 83 %), can be improved by relevant but also not relevant diets indicating that irritable bowel disease seems to be caused primarily by psychological disorders.

  10. Impaired glucose tolerance in rats fed low-carbohydrate, high-fat diets.

    Science.gov (United States)

    Bielohuby, Maximilian; Sisley, Stephanie; Sandoval, Darleen; Herbach, Nadja; Zengin, Ayse; Fischereder, Michael; Menhofer, Dominik; Stoehr, Barbara J M; Stemmer, Kerstin; Wanke, Rüdiger; Tschöp, Matthias H; Seeley, Randy J; Bidlingmaier, Martin

    2013-11-01

    Moderate low-carbohydrate/high-fat (LC-HF) diets are widely used to induce weight loss in overweight subjects, whereas extreme ketogenic LC-HF diets are used to treat neurological disorders like pediatric epilepsy. Usage of LC-HF diets for improvement of glucose metabolism is highly controversial; some studies suggest that LC-HF diets ameliorate glucose tolerance, whereas other investigations could not identify positive effects of these diets or reported impaired insulin sensitivity. Here, we investigate the effects of LC-HF diets on glucose and insulin metabolism in a well-characterized animal model. Male rats were fed isoenergetic or hypocaloric amounts of standard control diet, a high-protein "Atkins-style" LC-HF diet, or a low-protein, ketogenic, LC-HF diet. Both LC-HF diets induced lower fasting glucose and insulin levels associated with lower pancreatic β-cell volumes. However, dynamic challenge tests (oral and intraperitoneal glucose tolerance tests, insulin-tolerance tests, and hyperinsulinemic euglycemic clamps) revealed that LC-HF pair-fed rats exhibited impaired glucose tolerance and impaired hepatic and peripheral tissue insulin sensitivity, the latter potentially being mediated by elevated intramyocellular lipids. Adjusting visceral fat mass in LC-HF groups to that of controls by reducing the intake of LC-HF diets to 80% of the pair-fed groups did not prevent glucose intolerance. Taken together, these data show that lack of dietary carbohydrates leads to glucose intolerance and insulin resistance in rats despite causing a reduction in fasting glucose and insulin concentrations. Our results argue against a beneficial effect of LC-HF diets on glucose and insulin metabolism, at least under physiological conditions. Therefore, use of LC-HF diets for weight loss or other therapeutic purposes should be balanced against potentially harmful metabolic side effects.

  11. Lifelong Physical Activity Prevents Aging-Associated Insulin Resistance in Human Skeletal Muscle Myotubes via Increased Glucose Transporter Expression.

    Science.gov (United States)

    Bunprajun, Tipwadee; Henriksen, Tora Ida; Scheele, Camilla; Pedersen, Bente Klarlund; Green, Charlotte Jane

    2013-01-01

    Both aging and physical inactivity are associated with increased development of insulin resistance whereas physical activity has been shown to promote increased insulin sensitivity. Here we investigated the effects of physical activity level on aging-associated insulin resistance in myotubes derived from human skeletal muscle satellite cells. Satellite cells were obtained from young (22 yrs) normally active or middle-aged (56.6 yrs) individuals who were either lifelong sedentary or lifelong active. Both middle-aged sedentary and middle-aged active myotubes had increased p21 and myosin heavy chain protein expression. Interestingly MHCIIa was increased only in myotubes from middle-aged active individuals. Middle-aged sedentary cells had intact insulin-stimulated Akt phosphorylation however, the same cell showed ablated insulin-stimulated glucose uptake and GLUT4 translocation to the plasma membrane. On the other hand, middle-aged active cells retained both insulin-stimulated increases in glucose uptake and GLUT4 translocation to the plasma membrane. Middle-aged active cells also had significantly higher mRNA expression of GLUT1 and GLUT4 compared to middle-aged sedentary cells, and significantly higher GLUT4 protein. It is likely that physical activity induces a number of stable adaptations, including increased GLUT4 expression that are retained in cells ex vivo and protect, or delay the onset of middle-aged-associated insulin resistance. Additionally, a sedentary lifestyle has an impact on the metabolism of human myotubes during aging and may contribute to aging-associated insulin resistance through impaired GLUT4 localization.

  12. Hiperlipidemia e intolerancia a la glucosa en un grupo de pacientes infectados con VIH que reciben terapia antirretrovírica hiperactiva Hyperlipidemia and glucose intolerance in patients with HIV infection receiving antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Carlos José Castro-Sansores

    2006-06-01

    .OBJECTIVE: To determine the prevalence of secondary effects on lipid metabolism as a result of highly active antiretroviral therapy (HAART, as well as the impact of different types of antiretroviral regimens on lipids and glucose in a group of patients in Yucatan, Mexico MATERIAL AND METHODS: A cross-sectional study was conducted. A questionnaire created for this study was administered to each patient and total cholesterol, triglycerides and fasting glucose values were determined. The presence of hyperlipidemia and alterations in glucose were determined as well as their relation to the epidemiological variables obtained from the questionnaire RESULTS: A total of 211 subjects were studied [36 (17% of which were women and 175 (83% men]. Ninety-two patients (44% were found to have hyperlipidemia. Of these, 43 (20% had hypercholesterolemia (HC and 82 (39% hypertriglyceridaemia (HT. The presence of combined HC and HT was observed in 30 (14% patients. Nineteen (9% patients had alterations in glucose, six (3% diabetes mellitus and 13 (6% impaired glucose tolerance. The variables associated with the presence of hyperlipidemia were: levels of lymphocytes CD4>350 cells/µl (OR= 2.79 1.08-7.27, p= 0.03, male gender (OR= 3.6 1.4-9.12, p= 0.006 and the use of nucleoside-reverse transcriptase inhibitors (NRTI (OR= 3.1 1.2-8.1, p=0.01 CONCLUSIONS: Patients with HIV infection who receive HAART have an increased risk of presenting hyperlipidemia. In this group of patients the presence of hyperlipidemia and impaired glucose tolerance was significant. Unlike what has been indicated in most published reports, the alterations of lipids were associated more frequently with INTR use, for which it is concluded that the pathogeny of these alterations is not unique, that it is probable that concurrent effects exist between different antiretroviral drug families and that other host factors are involved in the pathogenic mechanism of these alterations.

  13. Synergetic Effects of Prenatal and Postnatal High Sucrose Intake on Glucose Tolerance and Hepatic Insulin Resistance in Rat Offspring.

    Science.gov (United States)

    Zhang, Pengjie; Zhu, Di; Zhang, Yueming; Li, Lingjun; Chen, Xionghui; Zhang, Wenna; Shi, Ruixiu; Tao, Jianying; Han, Bing; Xu, Zhice

    2018-03-01

    High sucrose intake during pregnancy is linked to type 2 diabetes mellitus and altered insulin resistance. This study attempts to ascertain whether prenatal high sucrose intake (20% sucrose) alleviates the detrimental effects of high postnatal sugar consumption in the offspring, and the molecular mechanisms are investigated using a rat model. High prenatal sucrose exposure increases the body weight of the offspring at 1-3 weeks of age. Exposure to both prenatal and postnatal high sucrose increases glucose tolerance in the 4-month-old adult offspring compared with offspring receiving other treatments. Postnatal high sucrose exposure suppresses food intake but increases the total daily caloric and fluid intake. Both fasting blood glucose and plasma triglyceride levels are increased, but the fasting insulin level is unaffected. Prenatal high sucrose intake enlarges pancreatic islet area; however, prenatal-plus-postnatal high sucrose exposure induces smaller pancreatic islets. IRS-1(S612) protein phosphorylation is significantly increased, and the GSK-3β (S9) phosphorylation level is reduced. Both prenatal and prenatal-plus-postnatal high sucrose exposure substantially affect biological functions related to insulin homeostasis. IRS-1(S612) protein phosphorylation appears to be a part of the molecular mechanism underlying these effects. These results add to the understanding of how high sucrose intake contributes to insulin resistance and diabetes pathogenesis and how postnatal nutrition and lifestyle may mitigate detrimental prenatal exposures. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. No Effect of Added Sugar Consumed at Median American Intake Level on Glucose Tolerance or Insulin Resistance

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    Joshua Lowndes

    2015-10-01

    Full Text Available Excess sugar consumption may promote adverse changes in hepatic and total body insulin resistance. Debate continues over the effects of sugars at more typically consumed levels and whether the identity of the sugar consumed is important. In the present study participants (20–60 years old were randomly assigned to one of five groups, three that consumed low fat milk with added fructose containing sugars in amounts equivalent to the 50th percentile of fructose consumption (US, one which consumed low-fat milk sweetened with glucose, and one unsweetened low-fat milk control group. The intervention lasted ten weeks. In the entire study population there was less than 1 kg increase in weight (73.6 ±13.0 vs. 74.5 ± 13.3 kg, p < 0.001, but the change in weight was comparable among groups (p > 0.05. There were no changes in fasting glucose (49 ± 0.4 vs. 5.0 ± 0.5 mmol/L, insulin (56.9 ± 38.9 vs. 61.8 ± 50.0 pmol/L, or insulin resistance, as measured by the Homeostasis Model Assessment method (1.8 ± 1.3 vs. 2.0 ± 1.5, all p > 0.05. These data suggest that added sugar consumed at the median American intake level does not produce changes in measures of insulin sensitivity or glucose tolerance and that no sugar has more deleterious effects than others.

  15. Genetic determinants of statin intolerance

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    Pollex Rebecca L

    2007-03-01

    Full Text Available Abstract Background Statin-related skeletal muscle disorders range from benign myalgias – such as non-specific muscle aches or joint pains without elevated serum creatinine kinase (CK concentration – to true myositis with >10-fold elevation of serum CK, to rhabdomyolysis and myoglobinuria. The genetic basis of statin-related muscle disorders is largely unknown. Because mutations in the COQ2 gene are associated with severe inherited myopathy, we hypothesized that common, mild genetic variation in COQ2 would be associated with inter-individual variation in statin intolerance. We studied 133 subjects who developed myopathy on statin monotherapy and 158 matched controls who tolerated statins without incident or complaint. Results COQ2 genotypes, based on two single nucleotide polymorphisms (SNP1 and SNP2 and a 2-SNP haplotype, all showed significant associations with statin intolerance. Specifically, the odds ratios (with 95% confidence intervals for increased risk of statin intolerance among homozygotes for the rare alleles were 2.42 (0.99 to 5.89, 2.33 (1.13 to 4.81 and 2.58 (1.26 to 5.28 for SNP1 and SNP2 genotypes, and the 2-SNP haplotype, respectively. Conclusion These preliminary pharmacogenetic results, if confirmed, are consistent with the idea that statin intolerance which is manifested primarily through muscle symptoms is associated with genomic variation in COQ2 and thus perhaps with the CoQ10 pathway.

  16. Statin Intolerance: the Clinician's Perspective.

    Science.gov (United States)

    Stulc, Tomáš; Ceška, Richard; Gotto, Antonio M

    2015-12-01

    Muscle problems and other adverse symptoms associated with statin use are frequent reasons for non-adherence and discontinuation of statin therapy, which results in inadequate control of hyperlipidemia and increased cardiovascular risk. However, most patients who experience adverse symptoms during statin use are able to tolerate at least some degree of statin therapy. Given the profound cardiovascular benefits derived from statins, an adequate practical approach to statin intolerance is, therefore, of great clinical importance. Statin intolerance can be defined as the occurrence of myalgia or other adverse symptoms that are attributed to statin therapy and that lead to its discontinuation. In reality, these symptoms are actually unrelated to statin use in many patients, especially in those with atypical presentations following long periods of treatment. Thus, the first step in approaching patients with adverse symptoms during the course of statin therapy is identification of those patients for whom true statin intolerance is unlikely, since most of these patients would probably be capable of tolerating adequate statin therapy. In patients with statin intolerance, an altered dosing regimen of very low doses of statins should be attempted and, if tolerated, should gradually be increased to achieve the highest tolerable doses. In addition, other lipid-lowering drugs may be needed, either in combination with statins, or alone, if statins are not tolerated at all. Stringent control of other risk factors can aid in reducing cardiovascular risk if attaining lipid treatment goals proves difficult.

  17. Is it just lactose intolerance?

    Science.gov (United States)

    Olivier, Celso Eduardo; Lorena, Sônia Letícia Silva; Pavan, Célia Regina; dos Santos, Raquel Acácia Pereira Gonçalves; dos Santos Lima, Regiane Patussi; Pinto, Daiana Guedes; da Silva, Mariana Dias; de Lima Zollner, Ricardo

    2012-01-01

    Acquired delayed-onset hypolactasia is a common autosomal recessive condition. Cow's milk allergies, conversely, are less common conditions that may manifest with equivalent symptoms and are able to simulate and/or aggravate lactose intolerance. This study was designed to evaluate the contribution of IgE-mediated cow's milk sensitization to the symptomatology of adult patients with lactose-free diet refractory lactose intolerance. Forty-six adult patients with lactose intolerance and persistent symptoms despite a lactose-free diet underwent skin-prick test to investigate cow's milk, goat's milk, and soy protein-specific-IgE. SDS-PAGE immunoblotting was used to investigate the presence of cow's milk protein-specific IgE. The percentage of patients who had skin reactions to whole cow's milk, alpha-lactalbumin, beta-lactoglobulin, caseins, goat's milk, and soy was 69.5, 36.9, 56.5, 56.5%, 54.3, and 50%, respectively. The percentage of patients with immunoblot-detected IgE specific for alpha-lactalbumin, beta-lactoglobulin, caseins, and bovine serum albumin was 21.7, 63, 67.3, and 2.1%, respectively. IgE-mediated sensitization to cow's milk is a frequent comorbidity in subjects with lactose-free diet refractory lactose intolerance and is worth consideration in patients with this condition.

  18. Acute mTOR inhibition induces insulin resistance and alters substrate utilization in vivo

    DEFF Research Database (Denmark)

    Kleinert, Maximilian; Sylow, Lykke; Fazakerley, Daniel J

    2014-01-01

    The effect of acute inhibition of both mTORC1 and mTORC2 on metabolism is unknown. A single injection of the mTOR kinase inhibitor, AZD8055, induced a transient, yet marked increase in fat oxidation and insulin resistance in mice, whereas the mTORC1 inhibitor rapamycin had no effect. AZD8055...... SIN1 rescued glycolysis. Glucose intolerance following AZD8055 administration was absent in mice lacking the mTORC2 subunit Rictor in muscle, and in vivo glucose uptake into Rictor-deficient muscle was reduced despite normal Akt activity. Taken together, acute mTOR inhibition is detrimental to glucose...

  19. Acute mTOR inhibition induces insulin resistance and alters substrate utilization in vivo

    DEFF Research Database (Denmark)

    Kleinert, Maximilian; Sylow, Lykke; Fazakerley, Daniel J.

    2014-01-01

    The effect of acute inhibition of both mTORC1 and mTORC2 on metabolism is unknown. A single injection of the mTOR kinase inhibitor, AZD8055, induced a transient, yet marked increase in fat oxidation and insulin resistance in mice, whereas the mTORC1 inhibitor rapamycin had no effect. AZD8055...... SIN1 rescued glycolysis. Glucose intolerance following AZD8055 administration was absent in mice lacking the mTORC2 subunit Rictor in muscle, and in vivo glucose uptake into Rictor-deficient muscle was reduced despite normal Akt activity. Taken together, acute mTOR inhibition is detrimental to glucose...

  20. Inhibition of Glucose-6-Phosphate Dehydrogenase Reverses Cisplatin Resistance in Lung Cancer Cells via the Redox System

    Science.gov (United States)

    Hong, Weipeng; Cai, Peiheng; Xu, Chuncao; Cao, Di; Yu, Weibang; Zhao, Zhongxiang; Huang, Min; Jin, Jing

    2018-01-01

    The pentose phosphate pathway (PPP), which branches from glycolysis, is correlated with cancer cell proliferation, survival and senescence. In this study, differences in the metabolic profile of the PPP and the redox status of human lung carcinoma A549 cells and cisplatin-induced multidrug-resistant A549/DDP cells were analyzed and evaluated. The results showed that A549/DDP cells exhibited differential PPP-derived metabolic features and redox-related molecules. A549/DDP cells exhibited increased expression and enzymatic activity of PPP enzyme glucose-6-phosphate dehydrogenase (G6PD). Furthermore, as demonstrated by the apoptotic rate, cell viability, and colony formation, inhibition of G6PD by siRNA or an inhibitor sensitized A549/DDP cells to cisplatin. Additionally, inhibition of G6PD restored the cisplatin sensitivity of A549/DDP cells by influencing redox homeostasis. In conclusion, overcoming cisplatin resistance through inhibition of G6PD could improve the understanding of the mechanisms underlying cisplatin-induced resistance in human lung cancer and may provide insights into the therapeutic potential of this treatment to combat resistance. PMID:29445340

  1. Interstitial insulin concentrations determine glucose uptake rates but not insulin resistance in lean and obese men.

    OpenAIRE

    Castillo, C; Bogardus, C; Bergman, R; Thuillez, P; Lillioja, S

    1994-01-01

    Insulin action and obesity are both correlated with the density of muscle capillary supply in humans. Since the altered muscle anatomy in the obese might affect interstitial insulin concentrations and reduce insulin action, we have cannulated peripheral lymphatic vessels in lean and obese males, and compared peripheral lymph insulin concentrations with whole body glucose uptake during a euglycemic, hyperinsulinemic clamp. Lymph insulin concentrations in the lower limb averaged only 34% of art...

  2. Childhood Maltreatment Is an Independent Risk Factor for Prediabetic Disturbances in Glucose Regulation.

    Science.gov (United States)

    Li, Li; Garvey, W Timothy; Gower, Barbara A

    2017-01-01

    Childhood maltreatment (CM) is shown to be associated with obesity and depression. However, the relationship of CM to prediabetic state is much less studied. We tested the hypothesis that CM increases the risk for prediabetic state due to glucose intolerance, reduced insulin sensitivity, and beta cell function. Oral glucose tolerance test (OGTT)-derived metabolic parameters of glucose tolerance, insulin sensitivity, and beta cell function were measured in 121 participants aged 19-60 years. CM exposure was measured using the Childhood Trauma Questionnaire. Blood samples were collected to measure the inflammatory factors. After controlling for age, race, gender, education, and depression, about 15% higher glucose area under the OGTT curve was observed in the CM group. CM individuals also exhibited impaired insulin sensitivity manifested by the Matsuda index and homeostasis model assessment of insulin resistance, which were correlated with CM severity after adjusting for depression. CM group showed approximately 50% lower disposition index. C-reactive protein and tumor necrosis factor-α levels were greater in the CM group vs. the non-CM group, and both were correlated with CM severity ( r  = 0.21, 0.23, respectively, both p  independent of depression and visceral fat mass. These data suggest an important relationship between CM and increased risk for prediabetic state due to glucose intolerance, impaired insulin sensitivity, and beta cell function. Our findings indicate that CM appears to be an independent risk factor for developing prediabetes.

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

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    Angela J. Hanson

    2016-03-01

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

  4. Increased Muscular 5α-Dihydrotestosterone in Response to Resistance Training Relates to Skeletal Muscle Mass and Glucose Metabolism in Type 2 Diabetic Rats.

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    Naoki Horii

    Full Text Available Regular resistance exercise induces skeletal muscle hypertrophy and improvement of glycemic control in type 2 diabetes patients. Administration of dehydroepiandrosterone (DHEA, a sex steroid hormone precursor, increases 5α-dihydrotestosterone (DHT synthesis and is associated with improvements in fasting blood glucose level and skeletal muscle hypertrophy. Therefore, the aim of this study was to investigate whether increase in muscle DHT levels, induced by chronic resistance exercise, can contribute to skeletal muscle hypertrophy and concomitant improvement of muscular glucose metabolism in type 2 diabetic rats. Male 20-week-old type 2 diabetic rats (OLETF were randomly divided into 3 groups: sedentary control, resistance training (3 times a week on alternate days for 8 weeks, or resistance training with continuous infusion of a 5α-reductase inhibitor (n = 8 each group. Age-matched, healthy nondiabetic Long-Evans Tokushima Otsuka (LETO rats (n = 8 were used as controls. The results indicated that OLETF rats showed significant decrease in muscular DHEA, free testosterone, DHT levels, and protein expression of steroidogenic enzymes, with loss of skeletal muscle mass and hyperglycemia, compared to that of LETO rats. However, 8-week resistance training in OLETF rats significantly increased the levels of muscle sex steroid hormones and protein expression of steroidogenic enzymes with a concomitant increase in skeletal muscle mass, improved fasting glucose level, and insulin sensitivity index. Moreover, resistance training accelerated glucose transporter-4 (GLUT-4 translocation and protein kinase B and C-ζ/λ phosphorylation. Administering the 5α-reductase inhibitor in resistance-trained OLETF rats resulted in suppression of the exercise-induced effects on skeletal muscle mass, fasting glucose level, insulin sensitivity index, and GLUT-4 signaling, with a decline in muscular DHT levels. These findings suggest that resistance training

  5. C-reactive protein causes insulin resistance in mice through Fcγ receptor IIB-mediated inhibition of skeletal muscle glucose delivery.

    Science.gov (United States)

    Tanigaki, Keiji; Vongpatanasin, Wanpen; Barrera, Jose A; Atochin, Dmitriy N; Huang, Paul L; Bonvini, Ezio; Shaul, Philip W; Mineo, Chieko

    2013-03-01

    Elevations in C-reactive protein (CRP) are associated with an increased risk of insulin resistance. Whether CRP plays a causal role is unknown. Here we show that CRP transgenic mice and wild-type mice administered recombinant CRP are insulin resistant. Mice lacking the inhibitory Fcγ receptor IIB (FcγRIIB) are protected from CRP-induced insulin resistance, and immunohistochemistry reveals that FcγRIIB is expressed in skeletal muscle microvascular endothelium and is absent in skeletal muscle myocytes, adipocytes, and hepatocytes. The primary mechanism in glucose homeostasis disrupted by CRP is skeletal muscle glucose delivery, and CRP attenuates insulin-induced skeletal muscle blood flow. CRP does not impair skeletal muscle glucose delivery in FcγRIIB(-/-) mice or in endothelial nitric oxide synthase knock-in mice with phosphomimetic modification of Ser1176, which is normally phosphorylated by insulin signaling to stimulate nitric oxide-mediated skeletal muscle blood flow and glucose delivery and is dephosphorylated by CRP/FcγRIIB. Thus, CRP causes insulin resistance in mice through FcγRIIB-mediated inhibition of skeletal muscle glucose delivery.

  6. Orthostatic hypertension: An underestimated cause of orthostatic intolerance.

    Science.gov (United States)

    Lee, Hyung; Kim, Hyun-Ah

    2016-04-01

    To investigate the frequency and mechanism of orthostatic hypertension (OHT) in patients with orthostatic intolerance. We retrospectively reviewed 1033 consecutive case series of orthostatic intolerance that underwent autonomic function tests including a head-up tilt test. OHT was defined as a paradoxical orthostatic increase in systolic blood pressure (BP) of at least 20 mmHg during the tilt. We collected autonomic parameters during the standardized autonomic function tests, which included the beat-to-beat derived hemodynamic parameters during the tilt table test and compared them with age and sex-matched normal controls and the orthostatic hypotension (OH) group with orthostatic symptoms. We identified 38 (3.7%) patients who showed OHT during the tilt. The increase in mean systolic BP during the tilt was 26.5 mmHg. Approximately 87% (33/38) of the OHT patients showed an increase in total peripheral resistance during the tilt. The mean increase in total peripheral resistance from a supine baseline was significantly higher in OHT patients compared to normal controls, but the OH group showed a decrease in mean total peripheral resistance during the tilt. A select few patients with orthostatic dizziness can show OHT during the tilt and they have signs of increased peripheral resistance. OHT may be considered in the differential diagnosis of orthostatic intolerance. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  7. Chronic intermittent hypoxia from pedo-stage decreases glucose transporter 4 expression in adipose tissue and causes insulin resistance.

    Science.gov (United States)

    Chen, Lin; Cao, Zhao-long; Han, Fang; Gao, Zhan-cheng; He, Quan-ying

    2010-02-20

    The persistence of sleep disordered breathing (SDB) symptoms after tonsil and/or adenoid (T&A) surgery are common in children with obstructive sleep apnea (OSA). We tested the hypothesis that disturbances of glucose transporters (GLUTs) in intraabdominal adipose tissue caused by chronic intermittent hypoxia (CIH) from the pedo-period could facilitate the appearance of periphery insulin resistance in Sprague-Dawley (SD) rats. We tested the hypothesis that the changes of GLUTs in adipose tissue may be one of the reasons for persistent SDB among clinical OSA children after T&A surgery. Thirty 21-day-old SD rats were randomly divided into a CIH group, a chronic continuous hypoxia (CCH) group, and a normal oxygen group (control group) and exposed for 40 days. The changes of weight, fasting blood glucose and fasting blood insulin levels were measured. Hyperinsulinemic-euglycemic clamp techniques were used to measure insulin resistance in each animal. Real-time quantitative PCR and Western blotting were used to measure GLUT mRNA and proteins in intraabdominal adipose tissue. Additional intraabdomial white adipose tissue (WAT) was also processed into paraffin sections and directly observed for GLUTs1-4 expression. When compared with control group, CIH increased blood fasting insulin levels, (245.07 +/- 53.89) pg/ml vs. (168.63 +/- 38.70) pg/ml, P = 0.038, and decreased the mean glucose infusion rate (GIR), (7.25 +/- 1.29) mg x kg(-1) x min(-1) vs. (13.34 +/- 1.54) mg x kg(-1) x min(-1), P < 0.001. GLUT-4 mRNA and protein expression was significantly reduced after CIH compared with CCH or normal oxygen rats, 0.002 +/- 0.002 vs. 0.039 +/- 0.009, P < 0.001; 0.642 +/- 0.073 vs. 1.000 +/- 0.103, P = 0.035. CIH in young rats could induce insulin resistance via adverse effects on glycometabolism. These findings emphasize the importance of early detection and treatment of insulin insensitivity in obese childhood OSA.

  8. Long‐term patient‐reported outcomes from an open‐label safety and efficacy study of bosutinib in Philadelphia chromosome–positive chronic myeloid leukemia patients resistant or intolerant to prior therapy

    Science.gov (United States)

    Mamolo, Carla M.; Gambacorti‐Passerini, Carlo; Cortes, Jorge E.; Brümmendorf, Tim H.; Su, Yun; Reisman, Arlene L.; Shapiro, Mark; Lipton, Jeff H.

    2017-01-01

    BACKGROUND Health‐related quality of life (HRQOL) in patients with chronic‐phase chronic myeloid leukemia (CML) is important because of the requirement for long‐term treatment. This study assessed HRQOL in bosutinib‐treated patients with Philadelphia chromosome–positive CML and resistance or intolerance to 1 (chronic‐phase second‐line [CP2L]) or more (chronic‐phase third‐line [CP3L]) tyrosine kinase inhibitors who had 264 weeks or more of follow‐up (ClinicalTrials.gov identifier NCT00261846). METHODS Patient‐reported HRQOL was assessed with the EuroQol 5‐Dimensions Questionnaire (EQ‐5D) and the Functional Assessment of Cancer Therapy–Leukemia (FACT‐Leu). RESULTS In total, 284 and 119 patients composed the CP2L and CP3L cohorts, respectively. At treatment completion, more than 50% of the patients in the CP2L and CP3L cohorts completed the EQ‐5D and FACT‐Leu assessments. The EQ‐5D and EQ‐5D visual analog scale scores were stable in both cohorts throughout treatment. The mean FACT‐Leu scores were generally stable over time but were lower in magnitude in the CP3L cohort versus the CP2L cohort. The FACT‐Leu scale scores of a subset of patients with chronic diarrhea (CP2L, n = 101; CP3L, n = 30) were similar to the scores of the larger cohorts. Minimally important differences (MIDs) from baseline for the FACT‐Leu scale scores were observed for the following: emotional well‐being (EWB), Functional Assessment of Cancer Therapy–General (FACT‐G) Total, FACT‐Leu Total, and Functional Assessment of Cancer Therapy Trial Outcome Index (FACT‐TOI) in the CP2L cohort and FACT‐Leu Total in the CP3L cohort. Among patients with chronic diarrhea, MIDs were observed for EWB, FACT‐G Total, FACT‐Leu Total, and FACT‐TOI in the CP2L cohort and for EWB, FACT‐G Total, and FACT‐Leu Total in the CP3L cohort. CONCLUSIONS HRQOL was maintained with long‐term bosutinib treatment for patients with CP2L and CP3L CML. Cancer

  9. Resistance of brain glucose metabolism to thiopental-induced CNS depression in newborn piglets.

    Science.gov (United States)

    Walter, Bernd; Eiselt, Michael; Cumming, Paul; Xiong, Guoming; Hinz, Rainer; Uthe, Susanne; Brust, Peter; Bauer, Reinhard

    2013-05-01

    The transition from mild sedation to deep anaesthesia is marked by the phenomenon of burst suppression (BS). FDG-PET studies show that the cerebral metabolic rate for glucose (CMRglc) declines dramatically with onset of BS in the adult brain. Global CMRglc increases substantially in the post-natal period and achieves its maximum in preadolescence. However, the impact of post-natal brain development on the vulnerability of CMRglc to the onset of BS has not been documented. Therefore, cerebral blood flow and metabolism were measured using a variant of the Kety-Schmidt method, in conjunction with quantitative regional estimation of brain glucose uptake by FDG-PET in groups of neonate and juvenile pigs, under a condition of light sedation or after induction of deep anaesthesia with thiopental. Quantification of simultaneous ECoG recordings was used to establish the correlation between anaesthesia-related changes in brain electrical activity and the observed cerebrometabolic changes. In the condition of light sedation the magnitude of CMRglc was approximately 20% higher in the older pigs, with the greatest developmental increase evident in the cerebral cortex and basal ganglia (Penergy demand of neonate brain during deep anaesthesia represents a reduced part of thiopental suppressing brain metabolism in neonates. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

  10. Food intolerance and mucosal inflammation.

    Science.gov (United States)

    Ohtsuka, Yoshikazu

    2015-01-01

    Most infants are immunologically active and are able to develop a tolerance to oligoclonal antigens by producing IgA, along with activation of regulatory T cells, in early infancy. Cytokines and their signaling molecules are important mediators in the intestine, regulating both oral tolerance and mucosal inflammation. This system works efficiently in most individuals, but for an as yet undefined reason, some people react to food and other proteins as though they were pathogens, with induction of chronic inflammation in the mucosa. The adverse reaction caused by ingested foods is defined as food intolerance. The clinical features of food intolerance include vomiting, diarrhea, bloody stool, eczema, failure to thrive, and a protean range of other symptoms. Intolerance can be divided into two categories depending on whether or not they are immunologically mediated. Food intolerance and mucosal inflammation are deeply related because tolerance cannot be established when there is an inflammation in the intestinal mucosa. Mast cells, eosinophils, mucosal lymphocytes, and epithelial cells are deeply involved and related to each other in the development of mucosal inflammation. Meanwhile, rectal bleeding in infancy is related to lymphoid hyperplasia with eosinophil infiltration into the colonic mucosa facilitated by C-C motif ligand 11 (CCL11, known as eotaxin-1) and C-X-C motif chemokine ligand 13 (CXCL13). Rectal bleeding in infancy may not be simply caused by allergic reactions against specific antigens, but may be due to migrated lymphocytes developing immunological tolerance; including IgA synthesizing, in the intestinal mucosa. © 2014 Japan Pediatric Society.

  11. Treating statin-intolerant patients

    Directory of Open Access Journals (Sweden)

    Pigna G

    2011-04-01

    Full Text Available Marcello Arca, Giovanni PignaAtherosclerosis Unit, Department of Internal Medicine and Allied Medical Specialities, Sapienza University of Rome, Rome, ItalyAbstract: Statins are effective in reducing cardiovascular events and are safe for almost all patients. Nevertheless, intolerance to statins is frequently faced in clinical practice. This is mostly due to muscular symptoms (myalgia with or without increase of plasma creatinine kinase and/or elevation of hepatic aminotransferases, which overall constitutes approximately two-thirds of reported adverse events during statin therapy. These side effects raise concerns in patients as well as in doctors and are likely to reduce patients' adherence and, as a consequence, the cardiovascular benefit. Therefore, it is mandatory that clinicians improve their knowledge on the clinical aspects of muscular and hepatic side effects of statin therapy as well as their ability to manage patients with statin intolerance. Besides briefly examining the clinical aspects and the mechanisms that are proposed to be responsible for the most common statin-associated side effects, the main purpose of this article is to review the available approaches to manage statin-intolerant patients. The first step is to determine whether the adverse events are indeed related to statin therapy. If so, lowering the dosage or changing statin, alternate dosing options, or the use of nonstatin compounds may be practical strategies. The cholesterol-lowering potency as well as the usefulness of these different approaches in treating statin-intolerant patients will be examined based on currently available data. However, the cardiovascular benefit of these strategies has not been well established, so their use has to be guided by a careful clinical assessment of each patient.Keywords: statin therapy, atorvastatin, rosuvastatin, aminotransferase levels, myopathy

  12. Role of insulin-like growth factor binding protein-3 in glucose and lipid metabolism

    Directory of Open Access Journals (Sweden)

    Ho-Seong Kim

    2013-03-01

    Full Text Available Insulin-like growth factor binding protein (IGFBP-3 has roles in modulating the effect of IGFs by binding to IGFs and inhibiting cell proliferation in an IGF-independent manner. Although recent studies have been reported that IGFBP-3 has also roles in metabolic regulation, their exact roles in adipose tissue are poorly understood. In this review, we summarized the studies about the biological roles in glucose and lipid metabolism. IGFBP-3 overexpression in transgenic mice suggested that IGFBP-3 results in glucose intolerance, and insulin resistance. IGFBP-3 knockout (KO mice exhibited normal insulin level and glucose response after glucose challenge. More recent study in IGFBP-3 KO mice with a high-fat diet demonstrated that IGFBP-3 KO mice exhibited elevated fasting glucose and insulin, but normal response to glucose challenge, suggesting that IGFBP-3 KO mice may induce insulin resistance even though preserved insulin sensitivity. In vitro and in vivo studies using 3T3-L1 adipocytes and rat, IGFBP-3 induced insulin resistance by inhibiting glucose uptake. In contrast, the reduced levels of IGFBP-3 in obesity might induce insulin resistance by suppression of IGFBP-3's anti-inflammatory function, suggesting IGFBP-3 has a protective effect on insulin resistance. Also, proteolysis of IGFBP-3 might contribute to the insulin resistance in obesity and type 2 diabetes mellitus. In addition, IGFBP-3 inhibited adipocyte differentiation, suggesting IGFBP-3 may contribute to the insulin insensitivity. Taken together, it is not yet certain that IGFBP-3 has a protective effect or enhancing effect on insulin resistance, and more studies will be needed to clarify the roles of IGFBP-3 in metabolic regulation.

  13. Gastro-Resistant Insulin Receptor-Binding Peptide from Momordica charantia Improved the Glucose Tolerance in Streptozotocin-Induced Diabetic Mice via Insulin Receptor Signaling Pathway.

    Science.gov (United States)

    Lo, Hsin-Yi; Li, Chia-Cheng; Chen, Feng-Yuan; Chen, Jaw-Chyun; Hsiang, Chien-Yun; Ho, Tin-Yun

    2017-10-25

    Momordica charantia is a commonly used food and has been used for the management of diabetes. Our previous study has identified an insulin receptor (IR)-binding protein (mcIRBP) from Momordica charantia. Here we identified the gastro-resistant hypoglycemic bioactive peptides from protease-digested mcIRBP. By in vitro digestion and IR kinase activity assay, we found that a 9-amino-acid-residue peptide, mcIRBP-9, was a gastro-resistant peptide that enhanced IR kinase activities. mcIRBP-9 activated IR signaling transduction pathway, which resulted in the phosphorylation of IR, the translocation of glucose transporter 4, and the uptake of glucose in cells. Intraperitoneal and oral administration of mcIRBP-9 stimulated the glucose clearance by 30.91 ± 0.39% and 32.09 ± 0.38%, respectively, in streptozotocin-induced diabetic mice. Moreover, a pilot study showed that daily ingestion of mcIRBP-9 for 30 days decreased the fasting blood glucose levels and glycated hemoglobin (HbA1c) levels by 23.62 ± 6.14% and 24.06 ± 1.53%, respectively. In conclusion, mcIRBP-9 is a unique gastro-resistant bioactive peptide generated after the digestion of mcIRBP. Furthermore, oral administration of mcIRBP-9 improves both the glucose tolerance and the HbA1c levels in diabetic mice via targeting IR signaling transduction pathway.

  14. Estimation of Insulin Resistance in Mexican Adults by the [13C]Glucose Breath Test Corrected for Endogenous Total CO2 Production

    Directory of Open Access Journals (Sweden)

    Erika Ibarra-Pastrana

    2012-01-01

    Full Text Available Objective. To evaluate the efficacy of the [13C]glucose breath test for measuring insulin resistance in Mexican adults with different glycemic states. Research Design and Methods. Fifty-eight adults underwent a [13C]glucose breath test with simultaneous measurement of total CO2 production by indirect calorimetry, at baseline and 90 minutes after the ingestion of 15 g of dextrose and 25 mg of [13C]glucose. HOMA was used as a marker of insulin resistance. Results. We found an inverse correlation between HOMA and the breath test δ13CO2 (‰, r=-0.41 (P=0.001. After adjusting for total CO2 production, correlations between HOMA and fasting glucose were less strong but remained significant. An ROC curve was constructed using δ13CO2 (‰ and HOMA values; the cut-off point was 9.99‰ δ13CO2, corresponding to a sensitivity of 80.0 (95% CI: 51.9, 95.7 and a specificity of 67.4 (95% CI: 51.5, 80.9. Conclusions. The [13C]glucose breath test is a simple noninvasive procedure but was not sufficiently robust for an accurate diagnosis of insulin resistance. Our findings suggest that the test might be helpful in identifying individuals who are not IR, which in turn may contribute to improved diabetes prevention.

  15. Estimation of Insulin Resistance in Mexican Adults by the [13C]Glucose Breath Test Corrected for Endogenous Total CO2 Production

    Science.gov (United States)

    Ibarra-Pastrana, Erika; Candia Plata, Maria del Carmen; Alvarez, Gerardo; Valencia, Mauro E.

    2012-01-01

    Objective. To evaluate the efficacy of the [13C]glucose breath test for measuring insulin resistance in Mexican adults with different glycemic states. Research Design and Methods. Fifty-eight adults underwent a [13C]glucose breath test with simultaneous measurement of total CO2 production by indirect calorimetry, at baseline and 90 minutes after the ingestion of 15 g of dextrose and 25 mg of [13C]glucose. HOMA was used as a marker of insulin resistance. Results. We found an inverse correlation between HOMA and the breath test δ 13CO2 (‰), r = −0.41 (P = 0.001). After adjusting for total CO2 production, correlations between HOMA and fasting glucose were less strong but remained significant. An ROC curve was constructed using δ 13CO2 (‰) and HOMA values; the cut-off point was 9.99‰ δ 13CO2, corresponding to a sensitivity of 80.0 (95% CI: 51.9, 95.7) and a specificity of 67.4 (95% CI: 51.5, 80.9). Conclusions. The [13C]glucose breath test is a simple noninvasive procedure but was not sufficiently robust for an accurate diagnosis of insulin resistance. Our findings suggest that the test might be helpful in identifying individuals who are not IR, which in turn may contribute to improved diabetes prevention. PMID:22848216

  16. Glucose transporter 1-mediated glucose uptake is limiting for B-cell acute lymphoblastic leukemia anabolic metabolism and resistance to apoptosis.

    Science.gov (United States)

    Liu, T; Kishton, R J; Macintyre, A N; Gerriets, V A; Xiang, H; Liu, X; Abel, E D; Rizzieri, D; Locasale, J W; Rathmell, J C

    2014-10-16

    The metabolic profiles of cancer cells have long been acknowledged to be altered and to provide new therapeutic opportunities. In particular, a wide range of both solid and liquid tumors use aerobic glycolysis to supply energy and support cell growth. This metabolic program leads to high rates of glucose consumption through glycolysis with secretion of lactate even in the presence of oxygen. Identifying the limiting events in aerobic glycolysis and the response of cancer cells to metabolic inhibition is now essential to exploit this potential metabolic dependency. Here, we examine the role of glucose uptake and the glucose transporter Glut1 in the metabolism and metabolic stress response of BCR-Abl+ B-cell acute lymphoblastic leukemia cells (B-ALL). B-ALL cells were highly glycolytic and primary human B-ALL samples were dependent on glycolysis. We show B-ALL cells express multiple glucose transporters and conditional genetic deletion of Glut1 led to a partial loss of glucose uptake. This reduced glucose transport capacity, however, was sufficient to metabolically reprogram B-ALL cells to decrease anabolic and increase catabolic flux. Cell proliferation decreased and a limited degree of apoptosis was also observed. Importantly, Glut1-deficient B-ALL cells failed to accumulate in vivo and leukemic progression was suppressed by Glut1 deletion. Similarly, pharmacologic inhibition of aerobic glycolysis with moderate doses of 2-deoxyglucose (2-DG) slowed B-ALL cell proliferation, but extensive apoptosis only occurred at high doses. Nevertheless, 2-DG induced the pro-apoptotic protein Bim and sensitized B-ALL cells to the tyrosine kinase inhibitor Dasatinib in vivo. Together, these data show that despite expression of multiple glucose transporters, B-ALL cells are reliant on Glut1 to maintain aerobic glycolysis and anabolic metabolism. Further, partial inhibition of glucose metabolism is sufficient to sensitize cancer cells to specifically targeted therapies, suggesting

  17. Insulin resistance, β-cell dysfunction and differences in curves of plasma glucose and insulin in the intermediate points of the standard glucose tolerance test in adults with cystic fibrosis.

    Science.gov (United States)

    Cano Megías, Marta; González Albarrán, Olga; Guisado Vasco, Pablo; Lamas Ferreiro, Adelaida; Máiz Carro, Luis

    2015-02-01

    diabetes has become a co-morbidity with a negative impact on nutritional status, lung function and survival in cystic fibrosis. To identify any changes in intermediate points after a 2-hour oral glucose tolerance test (OGTT), pancreatic β-cell dysfunction, and insulin resistance in cystic fibrosis-related diabetes. It was carried out a retrospective analysis in a cohort of 64 patients affected of cystic fibrosis, older than 14 years, using the first pathological OGTT. Peripheral insulin resistance was measured using the homeostasis model assessment for insulin resistance (HOMA- IR), and pancreatic β-cell function was calculated according to Wareham. Time to maximum plasma insulin and glucose levels and area under the curve (AUC0-120) were also measured. Twenty-eight women and 36 men with a mean age of 26.8 years were enrolled, of whom 26.7% had normal glucose tolerance (NGT), 18.3% cystic fibrosis-related diabetes without fasting hyperglycemia (CFRD w/o FPG), 10% indeterminate (INDET), and 45% impaired glucose tolerance (IGT). HOMA-IR values were not significantly different between the diagnostic categories. Patients with any pathological change had worse β cell function, with a significant delay in insulin secretion, although there were no differences in total insulin production (AUC0-120). Time to maximum glucose levels was significantly shorter in NGT patients as compared to other categories, with glucose AUC0-120 being higher in the different diagnostic categories as compared to NGT. In over half the cases, peak blood glucose levels during a standard OGTT are reached in the intermediate time points, rather than at the usual time of 120minutes. Patients with cystic fibrosis and impaired glucose metabolism have a delayed insulin secretion during the standard OGTT due to loss of first-phase insulin secretion, with no differences in total insulin production. Absence of significant changes in HOMA-IR suggests that β-cell dysfunction is the main pathogenetic

  18. Akt and Rac1 signalling are jointly required for insulin-stimulated glucose uptake in skeletal muscle and downregulated in insulin resistance

    DEFF Research Database (Denmark)

    Sylow, Lykke; Kleinert, Maximilian; Pehmøller, Christian

    2014-01-01

    Skeletal muscle plays a major role in regulating whole body glucose metabolism. Akt and Rac1 are important regulators of insulin-stimulated glucose uptake in skeletal muscle. However the relative role of each pathway and how they interact is not understood. Here we delineate how Akt and Rac1...... pathways signal to increase glucose transport independently of each other and are simultaneously downregulated in insulin resistant muscle. Pharmacological inhibition of Rac1 and Akt signalling was used to determine the contribution of each pathway to insulin-stimulated glucose uptake in mouse muscles....... The actin filament-depolymerizing agent LatrunculinB was combined with pharmacological inhibition of Rac1 or Akt, to examine whether either pathway mediates its effect via the actin cytoskeleton. Akt and Rac1 signalling were investigated under each condition, as well as upon Akt2 knockout and in ob/ob mice...

  19. Insulin resistance, blood glucose and inflammatory cytokine levels are risk factors for cardiovascular events in diabetic patients complicated with coronary heart disease.

    Science.gov (United States)

    Wang, Changmei; Li, Fang; Guo, Jingjing; Li, Congcong; Xu, Dashuai; Wang, Bin

    2018-02-01

    This study was designed to investigate the relation of insulin resistance, blood glucose and inflammatory cytokines with cardiovascular events in diabetic patients complicated with coronary heart disease (CHD). A total of 120 patients with diabetes mellitus type 2 (T2DM) complicated with CHD admitted to Jinan Central Hospital from January 2015 to March 2016 were enrolled in this study. There were 60 cases complicated with cardiovascular events and 60 had no history of cardiovascular events; there were 40 cases with abnormal blood glucose, 40 with insulin resistance and 40 with elevated inflammatory cytokines. Changes in the levels of blood glucose, fasting serum insulin and inflammatory cytokines as well as changes in the homeostasis model assessment of insulin resistance indexes (HOMA-IR) were recorded and compared among groups of patients. Besides, changes in the Global Registry of Acute Coronary Events (GRACE) risk score and the incidence rate of cardiovascular events were also detected and multivariate logistic regression analysis was conducted so as to identify relevant risk factors. Our results showed the fasting blood glucose and the 2 h postprandial blood glucose levels in the non-cardiovascular event group were lower than those in the cardiovascular event group (Pcardiovascular event group were significantly higher than those in the cardiovascular event group (Pcardiovascular event group were significantly lower than those in the cardiovascular event group (Prisk scores in patients with elevated inflammatory cytokines were higher than those in patients with insulin resistance and those in patients with blood glucose abnormalities (Pcardiovascular events in patients with blood glucose abnormalities was lower than that in patients with insulin resistance and that in patients with elevated inflammatory cytokines. There was a positive correlation between TNF-α and HOMA-IR (Prisk score (Prisk factors for cardiovascular events. Based on our findings, stronger

  20. Effect of cocoa and green tea on biomarkers of glucose regulation, oxidative stress, inflammation and hemostasis in obese adults at risk for insulin resistance

    Science.gov (United States)

    Flavanols may provide protection against insulin resistance, but little is known about the amounts and types of flavanols that may be efficacious. This study was designed to determine whether cocoa flavanols, over a range of intakes, improve biomarkers of glucose regulation, inflammation and hemost...

  1. Racl Signaling Is Required for Insulin-Stimulated Glucose Uptake and Is Dysregulated in Insulin-Resistant Murine and Human Skeletal Muscle

    DEFF Research Database (Denmark)

    Sylow, L.; Jensen, T. E.; Kleinert, M.

    2013-01-01

    The actin cytoskeleton-regulating GTPase Racl is required for insulin-stimulated GLUT4 translocation in cultured muscle cells. However, involvement of Racl and its downstream signaling in glucose transport in insulin-sensitive and insulin-resistant mature skeletal muscle has not previously been i...

  2. Peripheral insulin resistance rather than beta cell dysfunction accounts for geographical differences in impaired fasting blood glucose among sub-Saharan African individuals: findings from the RODAM study

    NARCIS (Netherlands)

    Meeks, Karlijn A. C.; Stronks, Karien; Adeyemo, Adebowale; Addo, Juliet; Bahendeka, Silver; Beune, Erik; Owusu-Dabo, Ellis; Danquah, Ina; Galbete, Cecilia; Henneman, Peter; Klipstein-Grobusch, Kerstin; Mockenhaupt, Frank P.; Osei, Kwame; Schulze, Matthias B.; Spranger, Joachim; Smeeth, Liam; Agyemang, Charles

    2017-01-01

    The aim of this study was to assess the extent to which insulin resistance and beta cell dysfunction account for differences in impaired fasting blood glucose (IFBG) levels in sub-Saharan African individuals living in different locations in Europe and Africa. We also aimed to identify determinants

  3. Peripheral insulin resistance rather than beta cell dysfunction accounts for geographical differences in impaired fasting blood glucose among sub-Saharan African individuals : findings from the RODAM study

    NARCIS (Netherlands)

    Meeks, Karlijn A C; Stronks, Karien; Adeyemo, Adebowale; Addo, Juliet; Bahendeka, Silver; Beune, Erik; Owusu-Dabo, Ellis; Danquah, Ina; Galbete, Cecilia; Henneman, Peter; Klipstein-Grobusch, Kerstin; Mockenhaupt, Frank P; Osei, Kwame; Schulze, Matthias B; Spranger, Joachim; Smeeth, Liam; Agyemang, Charles

    2017-01-01

    AIMS/HYPOTHESIS: The aim of this study was to assess the extent to which insulin resistance and beta cell dysfunction account for differences in impaired fasting blood glucose (IFBG) levels in sub-Saharan African individuals living in different locations in Europe and Africa. We also aimed to

  4. Effects of exercise training and diet on lipid kinetics during free fatty acid-induced insulin resistance in older obese humans with impaired glucose tolerance

    DEFF Research Database (Denmark)

    Solomon, Thomas; Haus, Jacob M; Marchetti, Christine M

    2009-01-01

    the effect of 12 wk of exercise training with and without caloric restriction on FFA turnover and oxidation (FFA(ox)) during acute FFA-induced insulin resistance. Sixteen obese subjects with impaired glucose tolerance were randomized to either a hypocaloric (n = 8; -598 +/- 125 kcal/day, 66 +/- 1 yr, 32...

  5. Lactose intolerance and other disaccharidase deficiency.

    Science.gov (United States)

    Tomar, Balvir S

    2014-09-01

    Intolerance to foods which contain lactose can cause a range of intestinal and systemic symptoms. These symptoms are caused by Lactase deficiency which is encoded by a single gene (LCT) of ≈ 50 kb located on chromosome 2q21. In some food items, lactose has been missed because of "hidden" lactose due to inadequately labeled, confusing diagnosis of lactose intolerance based on dietary restriction of dairy foods. Two polymorphisms, C/T13910 and G/A22018, linked to hypolactasia, correlate with breath hydrogen and symptoms after lactose. The key in the management of lactose intolerance is the dietary removal of lactose. Patients diagnosed as lactose intolerant must be advised of "risk" foods, inadequately labeled, including processed meats, bread, cake mixes, soft drinks, and lagers. This review highlights the types, symptoms and management of lactose intolerance and also highlights differences from milk allergy which closely mimics the symptoms of lactose intolerance.

  6. Exercise or physical activity and cognitive function in adults with type 2 diabetes, insulin resistance or impaired glucose tolerance: a systematic review.

    Science.gov (United States)

    Zhao, Ren Ru; O'Sullivan, Anthony J; Fiatarone Singh, Maria A

    2018-01-01

    Diabetes is an important risk factor for cognitive impairment. Although some studies suggest that physical exercise can minimize age-related cognitive declines or improve brain morphology or function, benefits in diabetes or impaired glucose tolerance are unclear. Therefore, our aim was to evaluate the efficacy of exercise or physical activity on cognition in adults with type 2 diabetes, insulin resistance or impaired glucose tolerance. An electronic search for studies published from the earliest record until February 2017 was conducted using Medline, EMBASE, SPORTDiscus, CINAHL, and PsycINFO. Any experimental or observational study designs were included, as long as they were conducted in individuals of any age with type 2 diabetes, insulin resistance or impaired glucose tolerance, and they directly examined exercise/physical activity effects on cognitive outcomes or the relationship between changes in cognition and changes in either insulin resistance and glucose homeostasis. Study quality was assessed using the PEDro scale; data on participant and intervention characteristics and outcomes were extracted. Six studies enrolling 2289 participants met the eligibility criteria. Quality was modest and effect sizes variable and mostly small or negligible. Overall, four of the six studies (67%) reported significant benefits of greater exercise/physical activity participation for some aspects of cognition, but only 26% of cognitive outcomes were significant across all trials. Clinical improvements in insulin resistance/glucose homeostasis were related to improvements in cognitive function in three studies. Overall results were inconsistent, with benefits varying across exercise types and cognitive domains. Literature does not provide evidence that physical activity or exercise interventions contribute to a better cognitive function in patients with type 2 diabetes or impaired glucose tolerance. Large-scale, long-term, robust randomized controlled trials are required to

  7. Hypocapnia and cerebral hypoperfusion in orthostatic intolerance

    Science.gov (United States)

    Novak, V.; Spies, J. M.; Novak, P.; McPhee, B. R.; Rummans, T. A.; Low, P. A.

    1998-01-01

    BACKGROUND AND PURPOSE: Orthostatic and other stresses trigger tachycardia associated with symptoms of tremulousness, shortness of breath, dizziness, blurred vision, and, often, syncope. It has been suggested that paradoxical cerebral vasoconstriction during head-up tilt might be present in patients with orthostatic intolerance. We chose to study middle cerebral artery (MCA) blood flow velocity (BFV) and cerebral vasoregulation during tilt in patients with orthostatic intolerance (OI). METHODS: Beat-to-beat BFV from the MCA, heart rate, CO2, blood pressure (BP), and respiration were measured in 30 patients with OI (25 women and 5 men; age range, 21 to 44 years; mean age, 31.3+/-1.2 years) and 17 control subjects (13 women and 4 men; age range, 20 to 41 years; mean age, 30+/-1.6 years); ages were not statistically different. These indices were monitored during supine rest and head-up tilt (HUT). We compared spontaneous breathing and hyperventilation and evaluated the effect of CO2 rebreathing in these 2 positions. RESULTS: The OI group had higher supine heart rates (Pfailed to show an increment. Among the cerebrovascular indices, all BFVs (systolic, diastolic, and mean) decreased significantly more, and cerebrovascular resistance (CVR) was increased in OI patients (Pindices were improved within 2 minutes of CO2 rebreathing. The relationships between CO2 and BFV and heart rate were well described by linear regressions, and the slope was not different between control subjects and patients with OI. CONCLUSIONS: Cerebral vasoconstriction occurs in OI during orthostasis, which is primarily due to hyperventilation, causing significant hypocapnia. Hypocapnia and symptoms of orthostatic hypertension are reversible by CO2 rebreathing.

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

    Science.gov (United States)

    Bronsart, Laura L; Contag, Christopher H

    2016-01-01

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

  9. Glucose allostasis

    DEFF Research Database (Denmark)

    Stumvoll, Michael; Tataranni, P Antonio; Stefan, Norbert

    2003-01-01

    (insulin resistance), we propose to use the term "glucose allostasis." Allostasis (stability through change) ensures the continued homeostatic response (stability through staying the same) to acute stress at some cumulative costs to the system. With increasing severity and over time, the allostatic load......In many organisms, normoglycemia is achieved by a tight coupling of nutrient-stimulated insulin secretion in the pancreatic beta-cell (acute insulin response [AIR]) and the metabolic action of insulin to stimulate glucose disposal (insulin action [M]). It is widely accepted that in healthy...

  10. Liberal intolerance in European education debates

    DEFF Research Database (Denmark)

    Olsen, Tore Vincents

    2017-01-01

    by subdividing it into four categories of liberal intolerance and demonstrates this by analysing six national debates on the accommodation of cultural and religious diversity in education. The analysis indicates that the nature of liberal intolerance understood as the combination of the four categories...... of liberal intolerance varies with the state tradition regarding religious neutrality of public institutions and the type of welfare state, but also that many liberal arguments for and against accommodation repeat themselves across national contexts....

  11. Statin intolerance: more questions than answers.

    Science.gov (United States)

    Guyton, John R; Campbell, Kristen B; Lakey, Wanda C

    2014-01-01

    The dramatic effectiveness of statins in improving the course of atherosclerotic cardiovascular disease tends to overshadow questions of statin intolerance. Thus after more than 25 years of clinical statin use, intolerance remains a poorly understood, frustrating issue for patients and providers. It has been extraordinarily difficult to define statin intolerance and its implications for clinical practice. Here, we briefly summarize current knowledge and raise questions that need to be addressed.

  12. Discrimination And Intolerance in the Art

    OpenAIRE

    Vitor Correia

    2014-01-01

    When the people speak about discrimination and intolerance, it is usually in reference to the racial, religious, political, sexual, age, problems, etc., and does not refer, or refers less, the discrimination and the intolerance determined by artistic reasons, or with these related : the age differences in art, the sexism in art, and the rejection of works of art. In this text we intend to show the existence of these forms of discrimination and intolerance, explain what they mean, its causes, ...

  13. Glucose metabolism determines resistance of cancer cells to bioenergetic crisis after cytochrome-c release.

    LENUS (Irish Health Repository)

    Huber, Heinrich J

    2011-03-01

    Many anticancer drugs activate caspases via the mitochondrial apoptosis pathway. Activation of this pathway triggers a concomitant bioenergetic crisis caused by the release of cytochrome-c (cyt-c). Cancer cells are able to evade these processes by altering metabolic and caspase activation pathways. In this study, we provide the first integrated system study of mitochondrial bioenergetics and apoptosis signalling and examine the role of mitochondrial cyt-c release in these events. In accordance with single-cell experiments, our model showed that loss of cyt-c decreased mitochondrial respiration by 95% and depolarised mitochondrial membrane potential ΔΨ(m) from -142 to -88 mV, with active caspase-3 potentiating this decrease. ATP synthase was reversed under such conditions, consuming ATP and stabilising ΔΨ(m). However, the direction and level of ATP synthase activity showed significant heterogeneity in individual cancer cells, which the model explained by variations in (i) accessible cyt-c after release and (ii) the cell\\'s glycolytic capacity. Our results provide a quantitative and mechanistic explanation for the protective role of enhanced glucose utilisation for cancer cells to avert the otherwise lethal bioenergetic crisis associated with apoptosis initiation.

  14. Discrimination And Intolerance in the Art

    Directory of Open Access Journals (Sweden)

    Vitor Correia

    2014-03-01

    Full Text Available When the people speak about discrimination and intolerance, it is usually in reference to the racial, religious, political, sexual, age, problems, etc., and does not refer, or refers less, the discrimination and the intolerance determined by artistic reasons, or with these related : the age differences in art, the sexism in art, and the rejection of works of art. In this text we intend to show the existence of these forms of discrimination and intolerance, explain what they mean, its causes, and its aftermath. We analyze the specificity of each of the discrimination and intolerance in the artistic field,  and the social weight they have in the world today.

  15. Discrimination And Intolerance in the Art

    Directory of Open Access Journals (Sweden)

    Vitor Correia

    2014-04-01

    Full Text Available When the people speak about discrimination and intolerance, it is usually in reference to the racial, religious, political, sexual, age, problems, etc., and does not refer, or refers less, the discrimination and the intolerance determined by artistic reasons, or with these related : the age differences in art, the sexism in art, and the rejection of works of art. In this text we intend to show the existence of these forms of discrimination and intolerance, explain what they mean, its causes, and its aftermath. We analyze the specificity of each of the discrimination and intolerance in the artistic field,  and the social weight they have in the world today.

  16. Selenoprotein P-neutralizing antibodies improve insulin secretion and glucose sensitivity in type 2 diabetes mouse models.

    Science.gov (United States)

    Mita, Yuichiro; Nakayama, Kaho; Inari, Shogo; Nishito, Yukina; Yoshioka, Yuya; Sakai, Naoko; Sotani, Kanade; Nagamura, Takahiro; Kuzuhara, Yuki; Inagaki, Kumi; Iwasaki, Miki; Misu, Hirofumi; Ikegawa, Masaya; Takamura, Toshinari; Noguchi, Noriko; Saito, Yoshiro

    2017-11-21

    Selenoprotein P (SeP) functions as a selenium (Se)-supply protein. SeP is identified as a hepatokine, promoting insulin resistance in type 2 diabetes. Thus, the suppression of Se-supply activity of SeP might improve glucose metabolism. Here, we develop an anti-human SeP monoclonal antibody AE2 as with neutralizing activity against SeP. Administration of AE2 to mice significantly improves glucose intolerance and insulin resistance that are induced by human SeP administration. Furthermore, excess SeP administration significantly decreases pancreas insulin levels and high glucose-induced insulin secretion, which are improved by AE2 administration. Epitope mapping reveals that AE2 recognizes a region of human SeP adjacent to the first histidine-rich region (FHR). A polyclonal antibody against the mouse SeP FHR improves glucose intolerance and insulin secretion in a mouse model of diabetes. This report describes a novel molecular strategy for the development of type 2 diabetes therapeutics targeting SeP.

  17. Intolerance and Violence Against Doctors.

    Science.gov (United States)

    Singh, Meharban

    2017-10-01

    Intolerance and grouse against doctors is a global phenomenon but India seems to lead the world in violence against doctors. According to World Health Organization, about 8-38% healthcare workers suffer physical violence at some point in their careers. Many more are verbally abused or threatened. Public is almost behaving like health sector terrorists. The spate of increasing attacks on doctors by damaging their property and causing physical injury is not acceptable by any civilized society. The public is becoming increasingly intolerant to a large number of social issues because of poor governance and vote bank politics. There is a need to arrest the development of further distrust between doctors and their patients/relatives, otherwise it will compromise all achievements of medical science and adversely affect healing capabilities of doctors. Rude and aggressive behavior of the patients or their family members, and arrogant and lackadaisical approach of the doctor, adversely affects the doctor-patient relationship and the outcome of the patient. The doctors, hospital administration and government must exercise "zero tolerance" with respect to acts of violence against healthcare professionals. It is possible to reduce the incidence of intolerance against doctors but difficult to eliminate it completely. The healthcare providers should demonstrate greater compassion and empathy with improved communication skills. The hospitals must have adequate infrastructure, facilities and staff to handle emergencies without delay and with due confidence and skills. The security of healthcare providers, especially in sensitive areas, should be improved by having adequate number of security guards, frisking facilities, extensive CCTV network and availability of "Quick response team" to handle unruly mob. In case of any grievances for alleged mismanagement, the public should handle the situation in a civilized manner and seek redressal through Medical Protection Act and legal

  18. [Food allergy or food intolerance?].

    Science.gov (United States)

    Maître, S; Maniu, C-M; Buss, G; Maillard, M H; Spertini, F; Ribi, C

    2014-04-16

    Adverse food reactions can be classified into two main categories depending on wether an immune mechanism is involved or not. The first category includes immune mediated reactions like IgE mediated food allergy, eosinophilic oesophagitis, food protein-induced enterocolitis syndrome and celiac disease. The second category implies non-immune mediated adverse food reactions, also called food intolerances. Intoxications, pharmacologic reactions, metabolic reactions, physiologic, psychologic or reactions with an unknown mechanism belong to this category. We present a classification of adverse food reactions based on the pathophysiologic mechanism that can be useful for both diagnostic approach and management.

  19. estigma tolerable al estigma intolerable

    Directory of Open Access Journals (Sweden)

    Nelson Arteaga Botello

    2006-01-01

    cristalización pasa por dos referentes de interacción y relación social al interior del espacio escolar. El primero está constituido por parámetros de normalidad y anormalidad a partir de la localización de estigmas. El segundo se encuentra, a contrapelo de la tendencia anterior, tratando de diluir los efectos de los estigmas al señalarlos como una práctica de tipificación social intolerable o inaceptable.

  20. Limited OXPHOS capacity in white adipocytes is a hallmark of obesity in laboratory mice irrespective of the glucose tolerance status

    Directory of Open Access Journals (Sweden)

    Theresa Schöttl

    2015-09-01

    Conclusion: Reduced mitochondrial respiratory capacity in white adipocytes is a hallmark of murine obesity irrespective of the glucose tolerance status. Impaired respiratory capacity in white adipocytes solely is not sufficient for the development of systemic glucose intolerance.

  1. Bariatric surgery in morbidly obese insulin resistant humans normalises insulin signalling but not insulin-stimulated glucose disposal.

    Directory of Open Access Journals (Sweden)

    Mimi Z Chen

    Full Text Available Weight-loss after bariatric surgery improves insulin sensitivity, but the underlying molecular mechanism is not clear. To ascertain the effect of bariatric surgery on insulin signalling, we examined glucose disposal and Akt activation in morbidly obese volunteers before and after Roux-en-Y gastric bypass surgery (RYGB, and compared this to lean volunteers.The hyperinsulinaemic euglycaemic clamp, at five infusion rates, was used to determine glucose disposal rates (GDR in eight morbidly obese (body mass index, BMI=47.3 ± 2.2 kg/m(2 patients, before and after RYGB, and in eight lean volunteers (BMI=20.7 ± 0.7 kg/m2. Biopsies of brachioradialis muscle, taken at fasting and insulin concentrations that induced half-maximal (GDR50 and maximal (GDR100 GDR in each subject, were used to examine the phosphorylation of Akt-Thr308, Akt-473, and pras40, in vivo biomarkers for Akt activity.Pre-operatively, insulin-stimulated GDR was lower in the obese compared to the lean individuals (P<0.001. Weight-loss of 29.9 ± 4 kg after surgery significantly improved GDR50 (P=0.004 but not GDR100 (P=0.3. These subjects still remained significantly more insulin resistant than the lean individuals (p<0.001. Weight loss increased insulin-stimulated skeletal muscle Akt-Thr308 and Akt-Ser473 phosphorylation, P=0.02 and P=0.03 respectively (MANCOVA, and Akt activity towards the substrate PRAS40 (P=0.003, MANCOVA, and in contrast to GDR, were fully normalised after the surgery (obese vs lean, P=0.6, P=0.35, P=0.46, respectively.Our data show that although Akt activity substantially improved after surgery, it did not lead to a full restoration of insulin-stimulated glucose disposal. This suggests that a major defect downstream of, or parallel to, Akt signalling remains after significant weight-loss.

  2. Overexpression of the dual-specificity phosphatase MKP-4/DUSP-9 protects against stress-induced insulin resistance

    DEFF Research Database (Denmark)

    Emanuelli, Brice; Eberlé, Delphine; Suzuki, Ryo

    2008-01-01

    Insulin resistance, a hallmark of type 2 diabetes and obesity, is associated with increased activity of MAP and stress-activated protein (SAP) kinases, which results in decreased insulin signaling. Our goal was to investigate the role of MAP kinase phosphatase-4 (MKP-4) in modulating this process......, improved glucose intolerance, decreased expression of gluconeogenic and lipogenic genes, and reduced hepatic steatosis. Thus, MKP-4 has a protective effect against the development of insulin resistance through its ability to dephosphorylate and inactivate crucial mediators of stress-induced insulin...... resistance, such as ERK and JNK, and increasing MKP-4 activity might provide a therapy for insulin-resistant disorders....

  3. Food Intolerance vs. Food Allergy: What's the Difference?

    Science.gov (United States)

    ... the difference? What's the difference between a food intolerance and a food allergy? Answers from James T C Li, ... common, but most are caused by a food intolerance rather than a food allergy. A food intolerance ...

  4. What People with Lactose Intolerance Need to Know about Osteoporosis

    Science.gov (United States)

    ... People With Lactose Intolerance Need to Know About Osteoporosis What Is Lactose Intolerance? Lactose intolerance is a ... Health Strategies Resources For Your Information What Is Osteoporosis? Osteoporosis is a condition in which bones become ...

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

    Directory of Open Access Journals (Sweden)

    Sandra Lucinei Balbo

    2012-12-01

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

  6. Intestinal Ralstonia pickettii augments glucose intolerance in obesity

    DEFF Research Database (Denmark)

    Udayappan, Shanthadevi D; Kovatcheva-Datchary, Petia; Bakker, Guido J

    2017-01-01

    An altered intestinal microbiota composition has been implicated in the pathogenesis of metabolic disease including obesity and type 2 diabetes mellitus (T2DM). Low grade inflammation, potentially initiated by the intestinal microbiota, has been suggested to be a driving force in the development ...

  7. Prevalence and determinants of glucose intolerance among HIV ...

    African Journals Online (AJOL)

    ±SD age of 38±15 years were HAARTtreated; while 200 (61 males and 139 females) with mean±SD age of 33±17 years were HAART-naive. Overall, the prevalence of GI was 40.4% (IFG) 19.5%, IGT 11.5% and DM 9.4%. The prevalence of ...

  8. Natural history and physiological determinants of changes in glucose tolerance in a non-diabetic population: the RISC Study

    DEFF Research Database (Denmark)

    Ferrannini, E; Natali, A; Muscelli, E

    2011-01-01

    The natural history and physiological determinants of glucose intolerance in subjects living in Europe have not been investigated. The aim of this study was to increase our understanding of this area.......The natural history and physiological determinants of glucose intolerance in subjects living in Europe have not been investigated. The aim of this study was to increase our understanding of this area....

  9. Inflammatory Properties of Diet and Glucose-Insulin Homeostasis in a Cohort of Iranian Adults

    Directory of Open Access Journals (Sweden)

    Nazanin Moslehi

    2016-11-01

    Full Text Available We aimed to investigate associations of the dietary inflammatory index (DII with glucose-insulin homeostasis markers, and the risk of glucose intolerance. This cross-sectional study included 2975 adults from the Tehran Lipid and Glucose Study. Fasting plasma glucose (FPG, 2-h post-load glucose (2h-PG, and fasting serum insulin were measured. Homeostatic model assessment of insulin resistance index (HOMA-IR and β-cell function (HOMA-B, and the quantitative insulin sensitivity check index (QUICKI were calculated. Glucose tolerance abnormalities included impaired fasting glucose (IFG, impaired glucose tolerance (IGT, and type 2 diabetes (T2DM. DII scores were positively associated with 2h-PG (β = 0.04; p = 0.05. There was no significant linear trend across quartiles of DII for adjusted means of glucose-insulin homeostasis markers. Participants in the highest quartile of DII score tended to have higher FPG compared to those in the second quartile of DII score (5.46 vs. 5.38 mmol/L, p = 0.07 and higher fasting insulin and HOMA-IR compared to those in the lowest quartile (8.52 vs. 8.12 µU/mL for fasting insulin, p = 0.07; 2.06 vs. 1.96 for HOMA-IR, p = 0.08. No significant associations were observed between DII and risk of IFG, IGT, T2DM, and insulin resistance. Among glucose-insulin homeostasis markers, DII had a positive weak association only with 2h-PG.

  10. Effect of interferon treatment on glucose metabolism in children with chronic hepatitis B infection.

    Science.gov (United States)

    Kuloğlu, Zarife; Kansu, Aydan; Berberoğlu, Merih; Demirçeken, Fulya; Ocal, Gönül; Girgin, Nurten

    2004-03-01

    Interferon is known to have some effects on glucose metabolism, but this issue has not been investigated in children with chronic hepatitis B infection. The aim of this study was to investigate the impact of interferon on glucose metabolism and to investigate whether autoimmunity has a role in the pathogenesis. Fourteen patients (9 male, 6.3+/-2.7 years) with children with chronic hepatitis B infection were prospectively evaluated. They received interferon 10 MU/m2 for six months. Vral glucose tolerance test, fasting insulin and C-peptide, postprandial insulin and C-peptide, anti-GAD antibody, HOMA-IR and glucose/insulin ratio were measured before and after treatment. Before interferon, oral glucose tolerance test showed glucose intolerance in two patients (14.5%) and hypoglycemia in one patient (7.1%). One patient had hyperinsulinemia and insulin resistance (7.1%), and four patients had hypoinsulinemia and insulin hypersensitivity (28.5%). After interferon, oral glucose tolerance test was normal in 13 patients (92.8%). Abnormal oral glucose tolerance test persisted in the same patient, but no difference was found in insulin resistance. Hypoinsulinemia and insulin hypersensitivity were present in five patients (35.7%). DM related autoantibodies were negative in all patients before interferon; however, one patient, whose glucose metabolism was within normal limits, developed anti-GAD antibody after interferon. Children with children with chronic hepatitis B infection were shown to have hypoinsulinemia and insulin hypersensitivity. These children may have risk of progresssing to insuline dependent drabetes mellitus. We demonstrated that interferon did not seem to worsen glucose metabolism, but it had minimal positive impact on it. These results should be supported with other studies and interferon should be used carefully, especially in children with decreased beta cell reserve.

  11. Worry, Intolerance of Uncertainty, and Statistics Anxiety

    Science.gov (United States)

    Williams, Amanda S.

    2013-01-01

    Statistics anxiety is a problem for most graduate students. This study investigates the relationship between intolerance of uncertainty, worry, and statistics anxiety. Intolerance of uncertainty was significantly related to worry, and worry was significantly related to three types of statistics anxiety. Six types of statistics anxiety were…

  12. The differential diagnosis of food intolerance.

    Science.gov (United States)

    Zopf, Yurdagül; Baenkler, Hanns-Wolf; Silbermann, Andrea; Hahn, Eckhart G; Raithel, Martin

    2009-05-01

    More than 20% of the population in industrialized countries suffer from food intolerance or food allergy. Selective literature search for relevant publications in PubMed and the Cochrane Library combined with further data from the interdisciplinary database on chronic inflammatory and allergic diseases of the Erlangen University Hospital. The majority of cases of food intolerance (15% to 20%) are due to non-immunological causes. These causes range from pseudoallergic reactions to enzymopathies, chronic infections, and psychosomatic reactions that are associated with food intolerance. The prevalence of true food allergy, i.e., immunologically mediated intolerance reactions, is only 2% to 5%. The differential diagnosis of food intolerance is broad. Therefore, a structured diagnostic algorithm with input from multiple clinical disciplines should be applied. The treatment consists of eliminating the offending substance from the diet as well as medications and psychosomatic support, when indicated.

  13. Lactose malabsorption and intolerance: a systematic review on the diagnostic value of gastrointestinal symptoms and self-reported milk intolerance

    NARCIS (Netherlands)

    Jellema, P.; Schellevis, F. G.; van der Windt, D. A. W. M.; Kneepkens, C. M. F.; van der Horst, H. E.

    2010-01-01

    When lactose malabsorption gives rise to symptoms, the result is called 'lactose intolerance'. Although lactose intolerance is often bothersome for patients, once recognized it may be managed by simple dietary adjustments. However, diagnosing lactose intolerance is not straightforward, especially in

  14. High prevalence of methotrexate intolerance in juvenile idiopathic arthritis : development and validation of a methotrexate intolerance severity score

    NARCIS (Netherlands)

    Bulatović, Maja; Heijstek, Marloes W; Verkaaik, Marleen; van Dijkhuizen, E H Pieter; Armbrust, Wineke; Hoppenreijs, Esther P A; Kamphuis, Sylvia; Kuis, Wietse; Egberts, Toine C G; Sinnema, Gerben; Rademaker, Carin M A; Wulffraat, Nico M

    OBJECTIVE: To design and validate a new questionnaire for identifying patients with methotrexate (MTX) intolerance, and to determine the prevalence of MTX intolerance in patients with juvenile idiopathic arthritis (JIA) using this questionnaire. METHODS: The MTX Intolerance Severity Score (MISS)

  15. High prevalence of methotrexate intolerance in juvenile idiopathic arthritis: development and validation of a methotrexate intolerance severity score

    NARCIS (Netherlands)

    Bulatovic, M.; Heijstek, M.W.; Verkaaik, M.; Dijkhuizen, E.H. van; Armbrust, W.; Hoppenreijs, E.P.A.H.; Kamphuis, S.; Kuis, W.; Egberts, T.C.; Sinnema, G.; Rademaker, C.M.A.; Wulffraat, N.M.

    2011-01-01

    OBJECTIVE: To design and validate a new questionnaire for identifying patients with methotrexate (MTX) intolerance, and to determine the prevalence of MTX intolerance in patients with juvenile idiopathic arthritis (JIA) using this questionnaire. METHODS: The MTX Intolerance Severity Score (MISS)

  16. Lactose malabsorption and intolerance: a systematic review on the diagnostic value of gastrointestinal symptoms and self-reported milk intolerance

    NARCIS (Netherlands)

    Jellema, A.P.; Schellevis, F.G.; van der Windt, D.A.W.M.; Kneepkens, C.M.F.; van der Horst, H.E.

    2010-01-01

    Background: When lactose malabsorption gives rise to symptoms, the result is called 'lactose intolerance'. Although lactose intolerance is often bothersome for patients, once recognized it may be managed by simple dietary adjustments. However, diagnosing lactose intolerance is not straightforward,

  17. Lactose malabsorption and intolerance: a systematic review on the diagnostic value of gastrointestinal symptoms and self-reported milk intolerance.

    NARCIS (Netherlands)

    Jellema, P.; Schellevis, F.G.; Windt, D.A.W.M. van der; Kneepkens, C.M.F.; Horst, H.E. van der

    2010-01-01

    Background: When lactose malabsorption gives rise to symptoms, the result is called 'lactose intolerance'. Although lactose intolerance is often bothersome for patients, once recognized it may be managed by simple dietary adjustments. However, diagnosing lactose intolerance is not straightforward,

  18. Comparative effects of N-acetyl-L-cysteine and ramipril on arterial hypertension, insulin resistance, and oxidative stress in chronically glucose-fed rats.

    Science.gov (United States)

    El Midaoui, Adil; Ismael, Mahmoud Ali; Lu, Huogen; Fantus, I George; de Champlain, Jacques; Couture, Réjean

    2008-11-01

    Beneficial effects of an antioxidant (N-acetyl-L-cysteine, NAC) and an angiotensin I-converting enzyme (ACE) inhibitor (ramipril) were assessed in a rat model of insulin resistance induced by 10% glucose feeding for 20 weeks. Treatments with NAC (2 g/kg per day) and ramipril (1 mg/kg per day) were initiated at 16 weeks in the drinking fluid. Systolic blood pressure, plasma levels of insulin and glucose, and insulin resistance were significantly higher in rats treated with glucose for 20 weeks. This was associated with a higher production of superoxide anion and NADPH oxidase activity in aorta and liver and with a marked reduction in protein expression of skeletal muscle insulin receptor substrate-1 (IRS-1) in the gastrocnemius muscle. NAC prevented all these alterations. Although ramipril also reversed high blood pressure, it had a lesser effect on insulin resistance (including IRS-1) and blocked superoxide anion production only in aorta. Ramipril, in contrast to NAC, did not reduce NADPH oxidase activity in aorta and liver or plasma levels of 4-hydroxynonenal and malondialdehyde. Results suggest that the inhibition of the oxidative stress in hypertensive and insulin-resistant states contributes to the therapeutic effects of NAC and ramipril. Whereas NAC exerts effective antioxidant activity in multiple tissues, ramipril appears to preferentially target the vasculature.

  19. A mixture of apple pomace and rosemary extract improves fructose consumption-induced insulin resistance in rats: modulation of sarcolemmal CD36 and glucose transporter-4.

    Science.gov (United States)

    Ma, Peng; Yao, Ling; Lin, Xuemei; Gu, Tieguang; Rong, Xianglu; Batey, Robert; Yamahara, Johji; Wang, Jianwei; Li, Yuhao

    2016-01-01

    Apple pomace is a by-product of the processing of apple for juice, cider or wine preparation. Rosemary is a herb commonly used as spice and flavoring agent in food processing. Evidence suggests that both apple pomace and rosemary have rich bioactive molecules with numerous metabolic effects. To provide more information for using apple pomace and rosemary as functional foods for management of metabolism-associated disorders, the present study investigated the insulin-sensitizing effect of a mixture of apple pomace and rosemary extract (AR). The results showed that treatment with AR (500 mg/kg, daily, by gavage) for 5 weeks attenuated chronic liquid fructose consumption-induced increases in fasting plasma insulin concentration, the homeostasis model assessment of insulin resistance index and the adipose tissue insulin resistance index in rats. Mechanistically, AR suppressed fructose-induced acceleration of the clearance of plasma non-esterified fatty acids during oral glucose tolerance test, and decreased excessive triglyceride accumulation and the increased Oil Red O staining area in the gastrocnemius. Furthermore, AR restored fructose-induced overexpression of sarcolemmal CD36 that is known to contribute to etiology of insulin resistance by facilitating fatty acid uptake, and downregulation of sarcolemmal glucose transporter (GLUT)-4 that is the insulin-responsive glucose transporter. Thus, these results demonstrate that AR improves fructose-induced insulin resistance in rats via modulation of sarcolemmal CD36 and GLUT-4.

  20. Selection of improved Beauveria bassiana (Bals.) Vuill. strains based on 2-deoxy-D-glucose resistance and physiological analysis.

    Science.gov (United States)

    Robledo-Monterrubio, M; Alatorre-Rosas, R; Viniegra-González, G; Loera, O

    2009-07-01

    A series of 2-deoxy-D-glucose resistant mutants was obtained from wild type Beauveria bassiana 88 (Bb 88) by UV irradiation. Five mutants were characterized on Sabouraud Dextrose Agar and Chitin Agar for both radial extension rate (V(r)) and specific growth rate (micro). These values were obtained after adjusting morphometric data to a mathematical model used for filamentous fungi. Additionally, the protease and lipase potency index, conidial size, viability, and production levels were analyzed. The highest values for those physiological measurements were obtained by mutant 882.5 which, relative to Bb 88, showed a 30% reduction in half-life (LT(50)) on Sphenarium purpurascens, 70% on Acheta domesticus, and 71% on Tenebrio molitor larvae and adults. The half lethal concentration (LC(50)) on T. molitor larvae was 2.8 x 10(5)conidia/mL (con/mL) and 1.5 x 10(6)con/mL, respectively, for mutant 882.5 and Bb 88. This demonstrates that mutant 882.5 is more virulent, with up to an 80% reduction in LC(50). This work provides a convenient method for improving strains to be used in biocontrol as a suitable alternative to transgenic constructs.

  1. Noninvasive Ventilation Intolerance: Characteristics, Predictors, and Outcomes.

    Science.gov (United States)

    Liu, Jinhua; Duan, Jun; Bai, Linfu; Zhou, Lintong

    2016-03-01

    Noninvasive ventilation (NIV) intolerance is one reason for NIV failure. However, the characteristics, predictors, and outcomes of NIV intolerance are unclear. A prospective observational study was performed in the respiratory intensive care unit of a teaching hospital. Subjects with acute respiratory failure who used NIV were enrolled. Initially, continuous use of NIV was encouraged. However, if the subject could not tolerate NIV, it was used intermittently. NIV intolerance was defined as termination of NIV due to subject refusal to receive it because of discomfort, even after intermittent use was attempted. A total of 961 subjects were enrolled in the study. Of these, 50 subjects (5.2%) experienced NIV intolerance after a median 2.4 h of NIV support. Age (OR = 0.98, 95% CI 0.963-0.996) and heart rate (OR = 1.02, 95% CI 1.006-1.030) measured before NIV were 2 independent risk factors of NIV intolerance. After 1-2 h of NIV, independent risk factors of NIV intolerance were heart rate (OR = 1.03, 95% CI 1.016-1.044) and breathing frequency (OR = 1.06, 95% CI 1.027-1.099). Intolerant subjects had no improvement in mean arterial pressure, heart rate, or breathing frequency after the NIV intervention. Moreover, intolerant subjects had a higher intubation rate (44.0% vs 25.8%, P = .008) and higher mortality (34.0% vs 22.4%, P = .08). The three most common complaints were that NIV worsened subjects' distress (46%), that NIV resulted in dyspnea (26%), and that the flow or pressure of NIV was too strong to bear (16%). NIV intolerance worsened subjects' outcomes. Younger subjects with a high heart rate and breathing frequency may be more likely to experience NIV intolerance. Copyright © 2016 by Daedalus Enterprises.

  2. Nervous glucose sensing regulates postnatal β cell proliferation and glucose homeostasis

    OpenAIRE

    Tarussio, David; Metref, Salima; Seyer, Pascal; Mounien, Lourdes; Vallois, David; Magnan, Christophe; Foretz, Marc; Thorens, Bernard

    2013-01-01

    How glucose sensing by the nervous system impacts the regulation of β cell mass and function during postnatal development and throughout adulthood is incompletely understood. Here, we studied mice with inactivation of glucose transporter 2 (Glut2) in the nervous system (NG2KO mice). These mice displayed normal energy homeostasis but developed late-onset glucose intolerance due to reduced insulin secretion, which was precipitated by high-fat diet feeding. The β cell mass of adult NG2KO mice wa...

  3. Nervous glucose sensing regulates postnatal beta cell proliferation and glucose homeostasis

    OpenAIRE

    Tarussio, David; Metref, Salima; Seyer, Pascal; Mounien, Lourdes; Vallois, David; Magnan, Christophe; Foretz, Marc; Thorens, Bernard

    2014-01-01

    How glucose sensing by the nervous system impacts the regulation of â cell mass and function during postnatal development and throughout adulthood is incompletely understood. Here we studied mice with inactivation of glucose transporter 2 (Glut2) in the nervous system (NG2KO mice). These mice displayed normal energy homeostasis but developed late onset glucose intolerance due to reduced insulin secretion which was precipitated by high fat diet feeding. The â cell mass of adult NG2KO mice was ...

  4. Plasma Asprosin Concentrations Are Increased in Individuals with Glucose Dysregulation and Correlated with Insulin Resistance and First-Phase Insulin Secretion

    Directory of Open Access Journals (Sweden)

    Yuren Wang

    2018-01-01

    Full Text Available Background. Adipokines are reported to participate in many common pathologic processes of glucose dysregulation, such as insulin resistance, β-cell dysfunction, and chronic inflammation. Objective. To detect the concentrations of plasma asprosin in subjects with impaired glucose regulation (IGR and newly diagnosed type 2 diabetes (nT2DM and its relationship to parameters of glucose and lipid metabolism, insulin resistance, and pancreatic β-cell function. Methods. 143 eligible participants were included and were divided into three groups including normal glucose regulation (NGR, n=52, IGR (n=40, and nT2DM group (n=51. The intravenous glucose tolerance test (IVGTT and clinical and biochemical parameters were measured in all participants. Results. Plasma asprosin levels were higher in IGR (82.40 ± 91.06 ng/mL, P<0.001 and nT2DM (73.25 ± 91.69 ng/mL, P<0.001 groups compared with those in the NGR (16.22 ± 9.27 ng/mL group, especially in IGR subjects. Correlation analysis showed that plasma asprosin levels were positively correlated with waist circumference (Wc, fasting plasma glucose (FPG, postchallenge plasma glucose (2hPG, HbA1c, triglyceride (TG, and homeostasis model assessment for insulin resistance (HOMA-IR and negatively correlated with homeostasis model assessment for β-cell function (HOMA-β, area under the curve of the first-phase (0–10 min insulin secretion (AUC, acute insulin response (AIR, and glucose disposition index (GDI (all P<0.05. Multiple logistical regression analyses revealed that plasma asprosin concentrations were significantly correlated with IGR and nT2DM after controlling for age, sex, BMI, and WHR. Conclusions. Circulating asprosin might be a predictor of early diagnosis in DM and might be a potential therapeutic target for prediabetes and T2DM.

  5. Medicines, excipients and dietary intolerances.

    Science.gov (United States)

    2016-08-01

    Medicinal products contain not only active drugs but also other ingredients included for a variety of purposes and collectively known as excipients.(1) People who wish to avoid a specific substance because of an allergy or intolerance may ask a healthcare professional about the constituents of a medicine and whether an alternative is available. In a previous article we discussed the issues facing people who wish to avoid certain substances for religious or cultural reasons.(2) Here, we provide an overview of several dietary conditions and the pharmaceutical issues that need to be considered by healthcare professionals advising on the suitability of a medicine. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  6. Lipodystrophy defined by Fat Mass Ratio in HIV-infected patients is associated with a high prevalence of glucose disturbances and insulin resistance

    Directory of Open Access Journals (Sweden)

    Freitas Paula

    2012-08-01

    Full Text Available Abstract Introduction Combined antiretroviral therapy (cART in the treatment of HIV-1 infection has been associated with complications, including lipodystrophy, hyperlipidaemia, insulin resistance (IR and diabetes. Aims To compare the prevalence of glucose homeostasis disturbances and IR in HIV patients on cART according to the presence of lipodystrophy (defined clinically and by Fat Mass Ratio and different patterns of fat distribution and to establish their associations. Design Cross-sectional cohort study. Methods We evaluated body composition and IR and insulin sensitivity indexes in 345 HIV-infected adults. Results Patients with clinical lipodystrophy (CL had higher plasma glucose levels than patients without CL, without significant differences in plasma insulin levels, A1c, HOMA-IR, HOMA-B, QUICKI, or MATSUDA index. Patients with lipodystrophy defined by FMR had higher plasma glucose and insulin levels, A1c, HOMA-IR, QUICKI and MATSUDA than patients without lipodystrophy, without differences in HOMA-B. Higher insulin resistance (HOMA-IR ≥ 4 was present in patients with FMR-defined lipodystrophy. Patients with FMR-defined lipodystrophy had a higher prevalence of IFG, IGT and DM than patients without lipodystrophy. Significant associations between HOMA-IR and total, central and central/peripheral fat evaluated by CT at abdominal level were found and no association between HOMA-IR and peripheral fat. Association between HOMA-IR and total and trunk fat but no association with leg and arm fat (evaluated by DXA was found. Conclusions IR and glucose disturbances were significantly increased in patients with FMR-defined lipodystrophy. FMR lipodystrophy definition seems to be a more sensitive determinant of insulin resistance and glucose disturbances than clinical definition.

  7. Space Flight Orthostatic Intolerance Protection

    Science.gov (United States)

    Luty, Wei

    2009-01-01

    This paper summarizes investigations conducted on different orthostatic intolerance protection garments. This paper emphasizes on the engineering and operational aspects of the project. The current Shuttle pneumatic Anti-G Suit or AGS at 25 mmHg (0.5 psi) and customized medical mechanical compressive garments (20-30 mmHg) were tested on human subjects. The test process is presented. The preliminary results conclude that mechanical compressive garments can ameliorate orthostatic hypotension in hypovolemic subjects. A mechanical compressive garment is light, small and works without external pressure gas source; however the current garment design does not provide an adjustment to compensate for the loss of mass and size in the lower torso during long term space missions. It is also difficult to don. Compression garments that do not include an abdominal component are less effective countermeasures than garments which do. An early investigation conducted by the Human Adaptation and Countermeasures Division at Johnson Space Center (JSC) has shown there is no significant difference between the protection function of the AGS (at 77 mmHg or 1.5 psi) and the Russian anti-g suit, Kentavr (at 25 mmHg or 0.5 psi). Although both garments successfully countered hypovolemia-induced orthostatic intolerance, the Kentavr provided protection by using lower levels of compression pressure. This more recent study with a lower AGS pressure shows that pressures at 20-30 mmHg is acceptable but protection function is not as effective as higher pressure. In addition, a questionnaire survey with flight crewmembers who used both AGS and Kentavr during different missions was also performed.

  8. Statin intolerance - a question of definition.

    Science.gov (United States)

    Algharably, Engi Abdel-Hady; Filler, Iris; Rosenfeld, Stephanie; Grabowski, Katja; Kreutz, Reinhold

    2017-01-01

    Statin therapy is the backbone of pharmacologic therapy for low-density lipoproteins cholesterol lowering and plays a pivotal role in cardiovascular disease prevention. Statin intolerance is understood as the inability to continue using a statin to reduce individual cardiovascular risk sufficiently, due to the development of symptoms or laboratory abnormalities attributable to the initiation or dose escalation of a statin. Muscle symptoms are the most common side effects observed. Areas covered: The main aim of this article is to present a review on published definitions of statin intolerance. In addition, a brief review on clinical aspects and risk factors of statin intolerance is provided and features for a common definition for statin intolerance are suggested. Expert opinion: A definition of statin intolerance by major drug regulatory agencies is not available. In clinical studies, different definitions are chosen and results are not comparable; different medical associations do not agree on one common definition. There is an unmet need to establish a common definition of statin intolerance to ensure an appropriate clinical use of this important drug class. Further work is required to develop a consensus definition on statin intolerance that could have significant positive impact on both research and clinical management.

  9. γ-Oryzanol Enhances Adipocyte Differentiation and Glucose Uptake

    Directory of Open Access Journals (Sweden)

    Chang Hwa Jung

    2015-06-01

    Full Text Available Recent studies show that brown rice improves glucose intolerance and potentially the risk of diabetes, although the underlying molecular mechanisms remain unclear. One of the phytochemicals found in high concentration in brown rice is γ-oryzanol (Orz, a group of ferulic acid esters of phytosterols and triterpene alcohols. Here, we found that Orz stimulated differentiation of 3T3-L1 preadipocytes and increased the protein expression of adipogenic marker genes such as peroxisome proliferator-activated receptor gamma (PPAR-γ and CCAAT/enhanced binding protein alpha (C/EBPα. Moreover, Orz significantly increased the glucose uptake in insulin-resistant cells and translocation of glucose transporter type 4 (GLUT4 from the cytosol to the cell surface. To investigate the mechanism by which Orz stimulated cell differentiation, we examined its effects on cellular signaling of the mammalian target of rapamycin complex 1 (mTORC1, a central mediator of cellular growth and proliferation. The Orz treatment increased mTORC1 kinase activity based on phosphorylation of 70-kDa ribosomal S6 kinase 1 (S6K1. The effect of Orz on adipocyte differentiation was dependent on mTORC1 activity because rapamycin blocks cell differentiation in Orz-treated cells. Collectively, our results indicate that Orz stimulates adipocyte differentiation, enhances glucose uptake, and may be associated with cellular signaling mediated by PPAR-γ and mTORC1.

  10. [Progress on the research of lactose intolerance].

    Science.gov (United States)

    Chen, J; Sai, X Y

    2016-02-01

    Our group generalized the research development of lactose intolerance, both internationally and nationally. We systematically reviewed the pathogenesis, genetic polymorphisms of lactase deficiency, relevant progress of diagnostic methods and treatment. Through this systematic review, we undedrstood that there were insufficient research efforts made on understanding the epidemiological feature of lactose intolerance in this country. Relevant genetic mutations of people were also not clear, neither the development of simple and effective diagnosis method made. We should continue to extensively and deeply carry out the study regarding methods for early prevention and intervention on lactose intolerance.

  11. Serum lipoprotein ratios as markers of insulin resistance: A study among non-diabetic acute coronary syndrome patients with impaired fasting glucose

    Directory of Open Access Journals (Sweden)

    S Ray

    2015-01-01

    Full Text Available Background & objectives: Recent data suggest that insulin resistance can predict cardiovascular disease independently of the other risk factors, such as hypertension, visceral obesity or dyslipidaemia. However, the majority of available methods to evaluate insulin resistance are complicated to operate, expensive, and time consuming. This study was undertaken to assess whether serum lipoprotein ratios could predict insulin resistance in non-diabetic acute coronary syndrome (ACS patients. Methods: Ninety non-diabetic patients with impaired fasting glucose admitted with a diagnosis of ACS were included in the study. At the time of admission fasting glucose and insulin concentrations were measured. The homeostatic model assessment-insulin resistance (HOMA-IR was used for insulin resistance. The fasting serum total cholesterol (TC, triglycerides (TG and high density lipoprotein cholesterol (HDL-C levels were checked, and then TC/HDL-C and TG/HDL-C ratios were calculated. The areas under the curves (AUC of the receiver operating characteristic (ROC curves were used to compare the power of these serum lipoprotein ratios as markers. Results: Lipoprotein ratios were significantly higher in patients with HOMA-IR index > 2.5 as compared to patients with index <2.5 (P < 0.05. Both TG/HDL-C and TC/HDL-C ratios were significantly correlated with HOMA-IR (P<0.05. The area under the ROC curve of the TG/HDL-C and TC/HDL-C ratio for predicting insulin resistance was 0.80 (95% CI, 0.67 to 0.93, 0.78 (95% CI, 0.65 to 0.91, respectively. Interpretation & conclusions: The findings of this study demonstrate that serum lipoprotein ratios can provide a simple means of identifying insulin resistance and can be used as markers of insulin resistance and cardiovascular diseases risk in adult non-diabetic patients.

  12. High normal fasting glucose level in obese youth: a marker for insulin resistance and beta cell dysregulation.

    LENUS (Irish Health Repository)

    O'Malley, G

    2010-06-01

    A high but normal fasting plasma glucose level in adults is a risk factor for future development of type 2 diabetes mellitus and cardiovascular disease. We investigated whether normal fasting plasma glucose levels (<5.60 mmol\\/l) are associated with decreases in insulin sensitivity and beta cell function, as well as an adverse cardiovascular profile in obese youth.

  13. Fructose and/or Sorbitol Intolerance in a Subgroup of Lactose Intolerant Patients

    Directory of Open Access Journals (Sweden)

    SR Mishkin

    1994-01-01

    Full Text Available The diagnosis and treatment of lactose intolerance often does not resolve all the symptoms of postcibal bloating and flatulence. Included in this study were 104 lactose intolerant patients (71 female, 33 male who complained of residual postcibal discomfort in spite of adherence to and benefit from appropriate measures for their documented lactose intolerance (at least 20 ppm H2 after 25 g lactose as well as appropriate symptomatic discomfort. Clinical characteristics common to this group included: symptomatic diarrhea (12.5%, history of foreign travel (5.8%, endoscopic and pathological evidence of gastritis and helicobacter infection (19.2 and 8.7%, respectively, nonspecific abnormalities of small bowel follow-through (15.4%, Crohn’s disease (8.7% and colonic cliverticulosis (14.4%. Intolerance co fructose (at least 10 ppm H2 after 25 g fructose plus appropriate symptoms or sorbitol (at least 10 ppm H2 after 5 g sorbitol plus appropriate symptoms was documented in 17.3 and 18.3%, respectively. Intolerance to both fructose and sorbicol (administered as separate challenges, more than twice as common as intolerance to either one alone, occurred in 41.4% and was independent of sex. In conclusion, additional carbohydrate intolerances contribute to postcibal discomfort in more than 75% of lactose intolerant patients who remain symptomatic in spite of adherence to appropriate measures for this condition. While 62% of all patients had benefited significantly (greater than 50% from appropriate dietary measures and enzyme replacement for lactose intolerance, only 40% of those who were also fructose intolerant and 47% who were sorbitol intolerant benefited (greater than 50% from appropriate dietary measures (no enzyme replacement yet available for intolerance to these sugars.

  14. Growth differentiation factor 15 predicts future insulin resistance and impaired glucose control in obese nondiabetic individuals: results from the XENDOS trial.

    Science.gov (United States)

    Kempf, Tibor; Guba-Quint, Anja; Torgerson, Jarl; Magnone, Maria Chiara; Haefliger, Carolina; Bobadilla, Maria; Wollert, Kai C

    2012-11-01

    Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine that is increased in obesity and established type 2 diabetes. We assessed whether GDF-15 can predict future insulin resistance and impaired glucose control in obese nondiabetic individuals. Plasma GDF-15 concentrations were measured with an automated electrochemiluminescent immunoassay at baseline and after 4 years in 496 obese nondiabetic individuals (52% men, median age 48 years, median body mass index (BMI) 37.6 kg/m(2)) enrolled in the XENical in the prevention of Diabetes in Obese subjects (XENDOS) trial. The median GDF-15 concentration at baseline was 869 ng/l (interquartile range 723-1064 ng/l). GDF-15 was related to body weight, BMI, waist-to-hip ratio, and insulin resistance (homeostasis model assessment of insulin resistance (HOMA-IR)) (all P < 0.01). Changes in GDF-15 from baseline to 4 years were related to changes in body weight, BMI, waist-to-hip ratio, and HOMA-IR (all P < 0.05). Baseline GDF-15 was associated with the risk to have prediabetes or diabetes at 4 years by univariate analysis (odds ratio (OR) FOR 1 unit increase in ln GDF-15, 3.2; 95% confidence interval (CI): 1.7-6.1; P<0.001), and after multivariate adjustment for age, gender, treatment allocation (orlistat vs placebo), BMI, waist-to-hip ratio, and glucose control at baseline (OR 2.2; 95% CI: 1.1-4.7; P=0.026). Similarly, baseline GDF-15 was independently associated with HOMA-IR at 4 years (P=0.024). This first longitudinal study of GDF-15 in a large cohort of obese individuals indicates that GDF-15 is related to abdominal obesity and insulin resistance and independently associated with future insulin resistance and abnormal glucose control.

  15. Arrhythmia and exercise intolerance in Fontan patients

    DEFF Research Database (Denmark)

    Idorn, L; Juul, K; Jensen, A S

    2013-01-01

    BACKGROUND: Long-term survival after the Fontan procedure shows excellent results but is associated with a persistent risk of arrhythmias and exercise intolerance. We aimed to analyze the current burden of clinically relevant arrhythmia and severe exercise intolerance in Danish Fontan patients...... and estimated to 99.1% per year. Prevalence of clinically relevant arrhythmia and severe exercise intolerance increased significantly with age and was found in 32% and 85% of patients ≥20years, respectively. Thus, from survival data and logistic regression models the future prevalence of patients, clinically...... relevant arrhythmia and severe exercise intolerance were estimated, revealing a considerable augmentation. Furthermore, resting and maximum cardiac index, resting stroke volume index and pulmonary diffusing capacity decreased significantly with age while diastolic and systolic ventricular function...

  16. Lactose intolerance: from diagnosis to correct management.

    Science.gov (United States)

    Di Rienzo, T; D'Angelo, G; D'Aversa, F; Campanale, M C; Cesario, V; Montalto, M; Gasbarrini, A; Ojetti, V

    2013-01-01

    This review discusses one of the most relevant problems in gastrointestinal clinical practice: lactose intolerance. The role of lactase-persistence alleles the diagnosis of lactose malabsorption the development of lactose intolerance symptoms and its management. Most people are born with the ability to digest lactose, the major carbohydrate in milk and the main source of nutrition until weaning. Approximately, 75% of the world's population loses this ability at some point, while others can digest lactose into adulthood. Symptoms of lactose intolerance include abdominal pain, bloating, flatulence and diarrhea with a considerable intraindividual and interindividual variability in the severity. Diagnosis is most commonly performed by the non invasive lactose hydrogen breath test. Management of lactose intolerance consists of two possible clinical choice not mutually exclusive: alimentary restriction and drug therapy.

  17. Alteration of JNK-1 signaling in skeletal muscle fails to affect glucose homeostasis and obesity-associated insulin resistance in mice.

    Science.gov (United States)

    Pal, Martin; Wunderlich, Claudia M; Spohn, Gabriele; Brönneke, Hella S; Schmidt-Supprian, Marc; Wunderlich, F Thomas

    2013-01-01

    Obesity and associated metabolic disturbances, such as increased circulating fatty acids cause prolonged low grade activation of inflammatory signaling pathways in liver, skeletal muscle, adipose tissue and even in the CNS. Activation of inflammatory pathways in turn impairs insulin signaling, ultimately leading to obesity-associated type 2 diabetes mellitus. Conventional JNK-1 knock out mice are protected from high fat diet-induced insulin resistance, characterizing JNK-1-inhibition as a potential approach to improve glucose metabolism in obese patients. However, the cell type-specific role of elevated JNK-1 signaling as present during the course of obesity has not been fully elucidated yet. To investigate the functional contribution of altered JNK-1 activation in skeletal muscle, we have generated a ROSA26 insertion mouse strain allowing for Cre-activatable expression of a JNK-1 constitutive active construct (JNK(C)). To examine the consequence of skeletal muscle-restricted JNK-1 overactivation in the development of insulin resistance and glucose metabolism, JNK(C) mice were crossed to Mck-Cre mice yielding JNK(SM-C) mice. However, despite increased muscle-specific JNK activation, energy homeostasis and glucose metabolism in JNK(SM-C) mice remained largely unaltered compared to controls. In line with these findings, obese mice with skeletal muscle specific disruption of JNK-1, did not affect energy and glucose homeostasis. These experiments indicate that JNK-1 activation in skeletal muscle does not account for the major effects on diet-induced, JNK-1-mediated deterioration of insulin action and points towards a so far underappreciated role of JNK-1 in other tissues than skeletal muscle during the development of obesity-associated insulin resistance.

  18. Laktosemalabsorption og intolerance - Hvem, hvad og hvorfor

    DEFF Research Database (Denmark)

    Knudsen, Mikkel Malham; Olin, Anne Bille; Pærregaard, Anders

    2017-01-01

    During the last decade, lactose-free diets have become increasingly popular in the general population, either isolated or as a part of a cow's milk-free diet. However, health-related benefits from a lactose-free diet are only documented for individuals with clinical lactose intolerance due...... to decreased intestinal lactase activity and subsequent lactose malabsorption. In this paper we summarize the current knowledge of lactose intolerance regarding diagnostic procedures and treatment....

  19. Galactose intolerance and the risk of cataract.

    OpenAIRE

    Winder, A. F.; Fells, P.; Jones, R. B.; Kissun, R. D.; Menzies, I. S.; Mount, J. N.

    1982-01-01

    Cataracts may arise in association with various major and minor disorders restricting galactose metabolism, and the risk is broadly associated with the degree of galactose intolerance. A family is described in which a girl presented at the age of 7 3/4 years with cataracts, galactosuria, and partial deficiencies of the enzymes galactokinase and galactose-1-phosphate uridyl transferase. Galactose intolerance as determined by an oral test was impaired and fluctuated with variation in activity o...

  20. MODERN METHODS OF FOOD INTOLERANCE TESTING

    OpenAIRE

    M. Yu. Rosensteyn; A. Z. Rosensteyn; S. E. Kondakov; N. A. Cherevko

    2016-01-01

    Аn analytical review of modern methods of food intolerance diagnostics based on interpretation of markers used in the various tests is рresented. It is shown that tests based on observation of the reaction of specific antibodies of the immune system to food antigens tested, are the most accurate, reliable and representative for the diagnosis of food intolerance.

  1. Does Googling lead to statin intolerance?

    Science.gov (United States)

    Khan, Sarah; Holbrook, Anne; Shah, Baiju R

    2018-07-01

    The nocebo effect, where patients with expectations of adverse effects are more likely to experience them, may contribute to the high rate of statin intolerance found in observational studies. Information that patients read on the internet may be a precipitant of this effect. The objective of the study was to establish whether the number of websites about statin side effects found using Google is associated with the prevalence of statin intolerance. The prevalence of statin intolerance in 13 countries across 5 continents was established in a recent study via a web-based survey of primary care physicians and specialists. Using the Google search engine for each country, the number of websites about statin side effects was determined, and standardized to the number of websites about statins overall. Searches were restricted to pages in the native language, and were conducted after connecting to each country using a virtual private network (VPN). English-speaking countries (Australia, Canada, UK, USA) had the highest prevalence of statin intolerance and also had the largest standardized number of websites about statin side effects. The sample Pearson correlation coefficient between these two variables was 0.868. Countries where patients using Google are more likely to find websites about statin side effects have greater levels of statin intolerance. The nocebo effect driven by online information may be contributing to statin intolerance. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Putative identification of components in Zengye Decoction and their effects on glucose consumption and lipogenesis in insulin-induced insulin-resistant HepG2 cells.

    Science.gov (United States)

    Liu, Zhenzhen; Kuang, Wenhua; Xu, Xi; Li, Dandan; Zhu, Wufu; Lan, Zhou; Zhang, Xu

    2018-01-15

    Zengye Decoction (ZYD) is a well-known traditional medicine in China used for treating diseases associated with "Yin deficiency" such as diabetes. However, little information is available on its components, pharmacological effects and underlying mechanisms. This study was designed to identify its active components and evaluate the effects and mechanisms of ZYD on glucose consumption and lipogenesis in insulin-induced insulin-resistant (IR)-HepG2 cells. In this study, 45 compounds of ZYD were putatively identified, in which the iridoid glycosides such as catalpol, aucubin and harpagide were identified as the main components. The insulin-resistant (IR)-HepG2 cell model was established and the effect of ZYD at three doses (0.17, 0.5 and 1.5 μg/mL) on cell growth was evaluated with an IncuCyte™ live-cell imaging system. The effects of ZYD on glucose consumption and uptake were evaluated by glucose consumption and uptake assay. Meanwhile, the effect of ZYD on lipogenesis was investigated in IR-HepG2 cells by oil red O (ORO) staining. Western blot was applied to observe the changes in some of the key factors involved in glucose metabolism and lipogenesis. It was found that the ZYD at a dose of 1.5 μg/mL exhibited an inhibitory activity on IR-HepG2 cell growth. Besides, ZYD at doses of 0.5 and 1.5 μg/mL accelerated the glucose consumption, glucose uptake and reduced the lipogenesis in the IR-HepG2 cells. Western blot studies revealed that ZYD phosphorylated AMP-activated protein kinase α subunits (AMPKα), upregulated hexokinase (HK), phosphorylated acetyl-CoA carboxylase alpha (pACC1) and carnitine palmitoyltransferase 1A (CPT1A) in the IR-HepG2 cells. These results indicate ZYD promotes glucose consumption and uptake, and attenuates lipogenesis in IR-HepG2 cells, which may be involved in activating AMPK and regulating its downstream factors including HK, pACC1 and CPT1A. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Insulin resistance in tetraplegia but not in mid-thoracic paraplegia: is the mid-thoracic spinal cord involved in glucose regulation?

    Science.gov (United States)

    Bluvshtein, V; Korczyn, A D; Pinhas, I; Vered, Y; Gelernter, I; Catz, A

    2011-05-01

    Controlled experimental human study. To assess insulin resistance (IR) in tetraplegia and paraplegia, and the role of the spinal cord (SC) in glucose regulation. Laboratory of Spinal Research, Loewenstein Rehabilitation Hospital. Glucose and insulin levels and the heart rate variation spectral components LF (low frequency), HF (high frequency) and LF/HF were studied at supine rest, head-up tilt and after a standard meal in three groups: 13 healthy subjects, 7 patients with T(4)-T(6) paraplegia and 11 patients with C(4)-C(7) tetraplegia. Glucose and insulin increased significantly after the meal in all groups (Pinsulin level tended to accompany increases in LF/HF after the meal in the tetraplegia and control groups but not in the paraplegia group. Post-prandial IR appears in C(4)-C(7) but not in T(4)-T(6) SC injury. The results of the study, combined with previously published findings, are consistent with the hypotheses that IR is related to activation of the sympathetic nervous system, and that below T(4) the mid-thoracic SC is involved in the regulation of glucose and insulin levels.

  4. Dietary Salba (Salvia hispanica L) improves the altered metabolic fate of glucose and reduces increased collagen deposition in the heart of insulin-resistant rats.

    Science.gov (United States)

    Creus, Agustina; Benmelej, Adriana; Villafañe, Noelia; Lombardo, Yolanda B

    2017-06-01

    This study reports the effects of dietary Salba (chia) seeds on the mechanisms underlying impaired glucose metabolism in the heart of dyslipemic insulin-resistant rats fed a sucrose-rich diet (SRD). Wistar rats were fed a SRD for 3 months. Afterwards, half the animals continued with the SRD; in the other half's diet chia seeds replaced corn oil (CO) for three months (SRD+chia). In the control group, corn starch replaced sucrose. The replacement of CO by chia seeds in the SRD restored the activities of key enzymes involved in heart glucose metabolism decreasing fatty acid oxidation. Chia seeds normalized insulin stimulated GLUT-4 transporter, the abundance of IRS-1 and pAMPK, changed the profile of fatty acid phospholipids, reduced left-ventricle collagen deposition and normalized hypertension and dyslipidemia. New evidence is provided concerning the effects of dietary chia seeds in improving the altered metabolic fate of glucose in the heart of dyslipemic insulin-resistant rats. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Comparison of the effects on insulin resistance and glucose tolerance of 6-mo high-monounsaturated-fat, low-fat, and control diets

    DEFF Research Database (Denmark)

    Due, Anette; Larsen, Thomas M; Hermansen, Kjeld

    2008-01-01

    and after the 6-mo dietary intervention. All foods were provided by a purpose-built supermarket. RESULTS: After 6 mo, the MUFA diet reduced fasting glucose (-3.0%), insulin (-9.4%), and the homeostasis model assessment of insulin resistance score (-12.1%). Compared with the MUFA diet, the control diet......BACKGROUND: The effect of dietary fat and carbohydrate on glucose metabolism has been debated for decades. OBJECTIVE: The objective was to compare the effect of 3 ad libitum diets, different in type and amount of fat and carbohydrate, on insulin resistance and glucose tolerance subsequent to weight...... loss. DESIGN: Forty-six nondiabetic, obese [mean (+/-SEM) body mass index (in kg/m(2)): 31.2 +/- 0.3] men (n = 20) and premenopausal women (n = 26) aged 28.0 +/- 0.7 y were randomly assigned to 1 of 3 diets after > or = 8% weight loss: 1) MUFA diet (n = 16): moderate in fat (35-45% of energy) and high...

  6. Frequency of methotrexate intolerance in rheumatoid arthritis patients using methotrexate intolerance severity score (MISS questionnaire).

    Science.gov (United States)

    Fatimah, Nibah; Salim, Babur; Nasim, Amjad; Hussain, Kamran; Gul, Harris; Niazi, Sarah

    2016-05-01

    The objective of the study was to determine the frequency of methotrexate intolerance in rheumatoid arthritis (RA) patients by applying the methotrexate intolerance severity score (MISS) questionnaire and to see the effect of dose and concomitant use of other disease-modifying antirheumatic drugs (DMARDS) on methotrexate (MTX) intolerance. For the descriptive study, non-probability sampling was carried out in the Female Rheumatology Department of Fauji Foundation Hospital (FFH), Rawalpindi, Pakistan. One hundred and fifty diagnosed cases of RA using oral MTX were selected. The MISS questionnaire embodies five elements: abdominal pain, nausea, vomiting, fatigue and behavioural symptoms. The amplitude of each element was ranked from 0 to 3 being no complaint (0 points), mild (1 point), moderate (2 points) and severe (3 points). A cut-off score of 6 and above ascertained intolerance by the physicians. A total of 33.3 % of the subjects exhibited MTX intolerance according to the MISS questionnaire. Out of which, the most recurring symptom of all was behavioural with a value of 44 % whereas vomiting was least noticeable with a figure of 11 %. About 6.6 % of the women with intolerance were consuming DMARDs in conjunction with MTX. Those using the highest weekly dose of MTX (20 mg) had supreme intolerance with prevalence in 46.2 % of the patients. The frequency of intolerance decreased with a decrease in weekly dose to a minimum of 20 % with 7.5 mg of MTX. MTX intolerance has moderate prevalence in RA patients and if left undetected, the compliance to use of MTX as a first-line therapy will decrease. Methotrexate intolerance is directly proportional to the dose of MTX taken. Also, there is no upstroke seen in intolerance with the use of other disease-modifying agents.

  7. Regulation of glucose homeostasis by KSR1 and MARK2.

    Directory of Open Access Journals (Sweden)

    Paula J Klutho

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

  8. Insulin Resistance and Prognosis of Nondiabetic Patients With Ischemic Stroke: The ACROSS-China Study (Abnormal Glucose Regulation in Patients With Acute Stroke Across China).

    Science.gov (United States)

    Jing, Jing; Pan, Yuesong; Zhao, Xingquan; Zheng, Huaguang; Jia, Qian; Mi, Donghua; Chen, Weiqi; Li, Hao; Liu, Liping; Wang, Chunxue; He, Yan; Wang, David; Wang, Yilong; Wang, Yongjun

    2017-04-01

    Insulin resistance was common in patients with stroke. This study investigated the association between insulin resistance and outcomes in nondiabetic patients with first-ever acute ischemic stroke. Patients with ischemic stroke without history of diabetes mellitus in the ACROSS-China registry (Abnormal Glucose Regulation in Patients With Acute Stroke Across China) were included. Insulin resistance was defined as a homeostatis model assessment-insulin resistance (HOMA-IR) index in the top quartile (Q4). HOMA-IR was calculated as fasting insulin (μU/mL)×fasting glucose (mmol/L)/22.5. Multivariable logistic regression or Cox regression was performed to estimate the association between HOMA-IR and 1-year prognosis (mortality, stroke recurrence, poor functional outcome [modified Rankin scale score 3-6], and dependence [modified Rankin scale score 3-5]). Among the 1245 patients with acute ischemic stroke enrolled in this study, the median HOMA-IR was 1.9 (interquartile range, 1.1-3.1). Patients with insulin resistance were associated with a higher mortality risk than those without (adjusted hazard ratio, 1.68; 95% confidence interval, 1.12-2.53; P =0.01), stroke recurrence (adjusted hazard ratio, 1.57, 95% confidence interval, 1.12-2.19; P =0.008), and poor outcome (adjusted odds ratio, 1.42; 95% confidence interval, 1.03-1.95; P =0.03) but not dependence after adjustment for potential confounders. Higher HOMA-IR quartile categories were associated with a higher risk of 1-year death, stroke recurrence, and poor outcome ( P for trend =0.005, 0.005, and 0.001, respectively). Insulin resistance was associated with an increased risk of death, stroke recurrence, and poor outcome but not dependence in nondiabetic patients with acute ischemic stroke. © 2017 American Heart Association, Inc.

  9. Lactose intolerance in Indonesian children.

    Science.gov (United States)

    Hegar, Badriul; Widodo, Ariani

    2015-01-01

    "Lactose intolerance (LI)" is considered a common problem in Asians, and in many parts of the world. Its prevalence and age of manifestation varies between by Asian country, for possible genetic or cultural reasons. Studies in Indonesian children 3-15 years old (y) are available within the past two decades, using a pure lactose tolerance test. The prevalences of lactose malabsorption (LM) in pre-elementary (3-5 y), elementary (6-11 y), and junior high (12-14 y) school-children were 21.3%, 57.8%, and 73%, respectively. An increasing trend for LM prevalence was seen within the pre-elementary group, from 9.1% at 3 y to 28.6% at 5 y. The most frequent symptoms of LI in junior high school (JHS) group were abdominal pain (64.1%), abdominal distention (22.6%), nausea (15.1%), flatulence (5.7%), and diarrhea (1.9%), mostly within one hour of lactose ingestion. In children with regular and irregular milk drinking, LM occurred in 81.2% and 69.6%; LI was found in 56.2% and 52.1%, respectively. Most JHS children with dairy-associated recurrent abdominal pain (RAP) symptoms proved to be malabsorbers. Dairy products most related to RAP were milk and yogurt. LI was found in 81% of RAP children with abdominal pain most frequently, followed by nausea, bloating, diarrhea, borborygmi, and flatulence. Symp-tom onset occurred 30 minutes after lactose ingestion, especially nausea, bloating, and abdominal pain. In RAP children LI symptoms mostly found in breath hydrogen concentration>20 ppm. More LI symptoms were found in lactose malabsorbers, but symptoms were mild and generally disappeared in 7 hours, and in most by 15 hours.

  10. Sustained Decrease of Early-Phase Insulin Secretion in Japanese Women with Gestational Diabetes Mellitus who Developed Impaired Glucose Tolerance and Impaired Fasting Glucose Postpartum

    Directory of Open Access Journals (Sweden)

    Hiroko Katayama

    2015-01-01

    Full Text Available Objective The aim of this study was to compare glucose intolerance in the antenatal and the postpartum periods using a 75-g oral glucose tolerance test (OGTT in the Japanese women with gestational diabetes mellitus (GDM using a retrospective design. Patients and Methods Data were obtained from 85 Japanese women with GDM who delivered from April 2011 through April 2015 and who underwent an OGTT 6–14 weeks postpartum. The women were divided into two groups based on the results of the postpartum OGTT: one group with normal glucose tolerance (NGT and the other with impaired glucose tolerance (IGT as well as impaired fasting glucose (IFG. We analyzed the associations between postpartum IGT–IFG and various factors. Results Antenatally, a significant difference was observed between the groups only in the 1-hour plasma glucose level of the 75-g OGTT. Postpartum results of plasma glucose level were significantly higher at 0.5, 1, and 2 hours in the IGT–IFG group than those in the NGT group. Moreover, a significant decrease in the levels of 0.5-hour immunoreactive insulin and insulinogenic index was observed in the IGT–IFG group compared to those in the NGT group. Homeostasis model assessment-insulin resistance and homeostasis model assessment β-cell function of both groups were found to significantly decrease in the postpartum period; however, there was no significant change in the insulinogenic index of either group. Conclusions Our study clearly showed that the postpartum IGT and IFG levels of Japanese women with GDM are affected by impaired early-phase insulin secretion; however, insulin resistance promptly improves.

  11. Evaluation of organ-specific glucose metabolism by 18F-FDG in insulin receptor substrate-1 (IRS-1) knockout mice as a model of insulin resistance

    International Nuclear Information System (INIS)

    Cheng, Chao; Nakamura, Akinobu; Minamimoto, Ryogo; Shinoda, Kazuaki; Tateishi, Ukihide; Terauchi, Yasuo; Inoue, Tomio; Goto, Atsuhi; Kadowaki, Takashi

    2011-01-01

    Insulin resistance (IR) is a physiological condition in which the body produces insulin but does not result in a sufficient biological effect. Insulin resistance is usually asymptomatic but is associated with health problems and is a factor in the metabolic syndrome. The aim of the present study is to clarify organ-specific insulin resistance in normal daily conditions using [ 18 F]-2-fluoro-2-deoxy-D-glucose ([ 18 F]-FDG). The biodistribution of [ 18 F]-FDG was examined in insulin receptor substrate-1 (IRS-1) knockout mice, an animal model of skeletal muscle insulin resistance, and C57BL/6J (wild-type) mice with and without insulin loading. Mice received 0.5 MBq of [ 18 F]-FDG injected into the tail vein, immediately followed by nothing (control cohorts) or an intraperitoneal injection of 1.5 mU/g body weight of human insulin as an insulin loading test. Blood glucose concentrations for all of the experimental animals were assessed at 0, 20, 40, and 60 min post-injection. The mice were subsequently killed, and tissue was collected for evaluation of [ 18 F]-FDG biodistribution. The radioactivity of each organ was measured using a gamma counter. In the absence of insulin, the blood glucose concentrations of wild-type mice (132±26 mg/dl) and IRS-1 knockout mice (134±18 mg/dl) were not significantly different. Blood glucose concentrations decreased following insulin administration, with lower concentrations in wild-type mice than in knockout mice at 20, 40, and 60 min. A statistically significant difference in [ 18 F]-FDG uptake between wild-type mice and IRS-1 knockout mice was confirmed in the heart, abdominal muscle, and femoral muscle. With insulin loading, [ 18 F]-FDG uptake in the heart, back muscle, and abdominal muscle was significantly increased compared to without insulin loading in both wild-type mice and knockout mice. Our results showed that IR significantly affected [ 18 F]-FDG uptake in the heart in normal daily conditions. IR was associated with

  12. MicroRNA-21 regulates hepatic glucose metabolism by targeting FOXO1.

    Science.gov (United States)

    Luo, Ailing; Yan, Haibo; Liang, Jichao; Du, Chunyuan; Zhao, Xuemei; Sun, Lijuan; Chen, Yong

    2017-09-05

    Abnormal activation of hepatic gluconeogenesis is a major contributor to fasting hyperglycemia in type 2 diabetes; however, the potential role of microRNAs in gluconeogenesis remains unclear. Here, we showed that hepatic expression levels of microRNA-21 (miR-21) were decreased in db/db and high-fat diet (HFD)-induced diabetic mice. Adenovirus-mediated overexpression of miR-21 decreased the expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) and inhibited glucose production in primary mouse hepatocytes. Silencing of miR-21 reversed this effect. Overexpression of miR-21 in the livers of db/db and HFD-induced mice was able to suppress hepatic gluconeogenesis, subsequently decreasing blood glucose levels and improving glucose and insulin intolerance. Furthermore, overexpression of miR-21 in primary mouse hepatocytes and mouse livers decreased the protein levels of FOXO1 and increased hepatic insulin sensitivity. By contrast, silencing of miR-21 increased the protein levels of FOXO1, subsequently leading to a decrease in insulin sensitivity and impaired glucose intolerance in C57BL/6 mice fed with high-fat diet for 4weeks. Finally, we confirmed that FOXO1 was a potential target of miR-21. These results suggest that miR-21 is a critical regulator in hepatic gluconeogenesis and may provide a novel therapeutic target for treating insulin resistance and type 2 diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. 5-aminolevulinic acid (ALA) deficiency causes impaired glucose tolerance and insulin resistance coincident with an attenuation of mitochondrial function in aged mice.

    Science.gov (United States)

    Saitoh, Shinichi; Okano, Satoshi; Nohara, Hidekazu; Nakano, Hiroshi; Shirasawa, Nobuyuki; Naito, Akira; Yamamoto, Masayuki; Kelly, Vincent P; Takahashi, Kiwamu; Tanaka, Tohru; Nakajima, Motowo; Nakajima, Osamu

    2018-01-01

    In vertebrates, the initial step in heme biosynthesis is the production of 5-aminolevulinic acid (ALA) by ALA synthase (ALAS). ALA formation is believed to be the rate-limiting step for cellular heme production. Recently, several cohort studies have demonstrated the potential of ALA as a treatment for individuals with prediabetes and type-2 diabetes mellitus. These studies imply that a mechanism exists by which ALA or heme can control glucose metabolism. The ALAS1 gene encodes a ubiquitously expressed isozyme. Mice heterozygous null for ALAS1 (A1+/-s) experience impaired glucose tolerance (IGT) and insulin resistance (IR) beyond 20-weeks of age (aged A1+/-s). IGT and IR were remedied in aged A1+/-s by the oral administration of ALA for 1 week. However, the positive effect of ALA proved to be reversible and was lost upon termination of ALA administration. In the skeletal muscle of aged A1+/-s an attenuation of mitochondrial function is observed, coinciding with IGT and IR. Oral administration of ALA for 1-week brought about only a partial improvement in mitochondrial activity however, a 6-week period of ALA treatment was sufficient to remedy mitochondrial function. Studies on differentiated C2C12 myocytes indicate that the impairment of glucose metabolism is a cell autonomous effect and that ALA deficiency ultimately leads to heme depletion. This sequela is evidenced by a reduction of glucose uptake in C2C12 cells following the knockdown of ALAS1 or the inhibition of heme biosynthesis by succinylacetone. Our data provide in vivo proof that ALA deficiency attenuates mitochondrial function, and causes IGT and IR in an age-dependent manner. The data reveals an unexpected metabolic link between heme and glucose that is relevant to the pathogenesis of IGT/IR.

  14. Impact of vitamin D supplementation during a resistance training intervention on body composition, muscle function, and glucose tolerance in overweight and obese adults.

    Science.gov (United States)

    Carrillo, Andres E; Flynn, Michael G; Pinkston, Catherine; Markofski, Melissa M; Jiang, Yan; Donkin, Shawn S; Teegarden, Dorothy

    2013-06-01

    The impact of vitamin D supplementation in overweight and obese adults during resistance training on body composition, muscle function, and glucose tolerance was investigated. Twenty-three overweight and obese (age: 26.1±4.7 y; BMI: 31.3±3.2 kg/m(2); 25-hydroxyvitamin D: 19.3±7.2 ng/mL) adults were recruited for participation in a double-blind, placebo-controlled trial. Participants were randomly divided into vitamin D (VitD, 4000 IU/d; 5 females, 5 males) and placebo (PL; 7 females, 6 males) groups. Both groups completed 12 weeks of resistance training. 25-hydroxyvitamin D, parathyroid hormone, body composition, and glucose tolerance were assessed at baseline and 12 weeks. Muscle function (strength and power) was assessed at baseline, 4, 8, and 12 weeks. During the intervention, 25-hydroxyvitamin D increased and parathyroid hormone decreased in the VitD group (Pchange in 25-hydroxyvitamin D with the change in waist-to-hip ratio (R(2)=0.205, P=0.02). No other improvements were observed with supplementation. Vitamin D supplementation in overweight and obese adults during resistance training induced an early improvement in peak power, and elevated vitamin D status was associated with reduced waist-to-hip ratio. NCT01199926. Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  15. Dietary phytochemical index and the risk of insulin resistance and β-cell dysfunction: a prospective approach in Tehran lipid and glucose study.

    Science.gov (United States)

    Bahadoran, Zahra; Mirmiran, Parvin; Tohidi, Maryam; Azizi, Fereidoun

    2015-01-01

    In this study, we aimed to investigate the association of dietary phytochemical index (DPI) with insulin resistance, β-cell dysfunction, and insulin sensitivity. This longitudinal study was conducted on 1141 participants of the Tehran Lipid and Glucose Study. Dietary data were collected using a validated semi-quantitative FFQ with 168 food items at baseline and DPI was calculated. Fasting serum insulin and glucose were measured at baseline and again after a 3-year of follow-up. After 3-years of follow-up, the risk of hyperinsulinemia significantly decreased by 65 (OR = 0.35, 95% CI = 0.21-0.60) and 86% (OR = 0.14, 0.07-0.29), in the third and fourth quartile categories of DPI, respectively. The occurrence of insulin resistance and insulin insensitivity in participants with higher DPI was significantly lower than the others (OR = 0.48, 95% CI = 0.25-0.93 and OR = 0.11, 95% CI = 0.05-0.24, respectively). Higher consumption of phytochemical-rich foods may have protective effects against development of insulin resistance.

  16. [Lactose intolerance: past and present. Part 1].

    Science.gov (United States)

    Buzás, György Miklós

    2015-09-20

    Lactose intolerance is the most prevalent intestinal malabsorption disorder. After presentation of its history, the author describes the emergence of lactose intolerance during the evolution of species, and the biochemistry of lactose as well as features of human and bacterial lactase enzymes are then described. The unequal distribution of lactose intolerance in different continents and population is discussed, followed by presentation of past and present prevalence data in Hungary. Adult-type hypolactasia is caused by a polymorphism of the MCM6 gene located upstream from the lactase gene on the long arm of the chromosome 2. It can be determined with the polymerase chain reaction. The intestinal symptoms of lactose intolerance are well known, but its extra-intestinal manifestations are less recognised. Invasive diagnostic methods (determination of lactase activity from small intestinal biopsies, lactose tolerance test), are accurate, but have been replaced by the non-invasive methods; their gold standard is the H2 breath test. Genetic testing is being used more and more frequently in Hungary too, and, presumably, the methane breath test will be also available in the near future. Lactose intolerance can be accompanied by inflammatory bowel diseases, coeliac disease and irritable bowel syndrome; it could be established whether this association is causal or not in order to start a correct diet and therapy.

  17. Dissociation between fat-induced in vivo insulin resistance and proximal insulin signaling in skeletal muscle in men at risk for type 2 diabetes

    DEFF Research Database (Denmark)

    Storgaard, Heidi; Jensen, Christine B; Björnholm, Marie

    2004-01-01

    The effect of short- (2 h) and long-term (24 h) low-grade Intralipid infusion on whole-body insulin action, cellular glucose metabolism, and proximal components of the insulin signal transduction cascade was studied in seven obese male glucose intolerant first degree relatives of type 2 diabetic...... both short- and long-term fat infusion. Short- and long-term low-grade Intralipid infusion-induced (or enhanced) whole-body insulin resistance and impaired glucose metabolism in IGT relatives and matched control subjects. The fat-induced metabolic changes were not explained by impairment...... h Intralipid infusion (0.4 ml.kg(-1).min(-1)). Insulin-stimulated glucose disposal decreased approximately 25% after short- and long-term fat infusion in both IGT relatives and controls. Glucose oxidation decreased and lipid oxidation increased after both short- and long-term fat infusion in both...

  18. Gut microbiota modulation with norfloxacin and ampicillin enhances glucose tolerance in mice.

    Science.gov (United States)

    Membrez, Mathieu; Blancher, Florence; Jaquet, Muriel; Bibiloni, Rodrigo; Cani, Patrice D; Burcelin, Rémy G; Corthesy, Irène; Macé, Katherine; Chou, Chieh Jason

    2008-07-01

    Recent data suggest that the gut microbiota plays a significant role in fat accumulation. However, it is not clear whether gut microbiota is involved in the pathophysiology of type 2 diabetes. To assess this issue, we modulated gut microbiota via antibiotics administration in two different mouse models with insulin resistance. Results from dose-determination studies showed that a combination of norfloxacin and ampicillin, at a dose of 1 g/L, maximally suppressed the numbers of cecal aerobic and anaerobic bacteria in ob/ob mice. After a 2-wk intervention with the antibiotic combination, both ob/ob and diet-induced obese and insulin-resistant mice showed a significant improvement in fasting glycemia and oral glucose tolerance. The improved glycemic control was independent of food intake or adiposity because pair-fed ob/ob mice were as glucose intolerant as the control ob/ob mice. Reduced liver triglycerides and increased liver glycogen correlated with improved glucose tolerance in the treated mice. Concomitant reduction of plasma lipopolysaccharides and increase of adiponectin further supported the antidiabetic effects of the antibiotic treatment in ob/ob mice. In summary, modulation of gut microbiota ameliorated glucose tolerance of mice by altering the expression of hepatic and intestinal genes involved in inflammation and metabolism, and by changing the hormonal, inflammatory, and metabolic status of the host.

  19. Prevalence of Non-responders for Glucose Control Markers after 10 Weeks of High-Intensity Interval Training in Adult Women with Higher and Lower Insulin Resistance.

    Science.gov (United States)

    Álvarez, Cristian; Ramírez-Campillo, Rodrigo; Ramírez-Vélez, Robinson; Izquierdo, Mikel

    2017-01-01

    Background: Exercise training improves performance and biochemical parameters on average, but wide interindividual variability exists, with individuals classified as responders (R) or non-responders (NRs), especially between populations with higher or lower levels of insulin resistance. This study assessed the effects of high-intensity interval training (HIIT) and the prevalence of NRs in adult women with higher and lower levels of insulin resistance. Methods: Forty adult women were assigned to a HIIT program, and after training were analyzed in two groups; a group with higher insulin resistance (H-IR, 40 ± 6 years; BMI: 29.5 ± 3.7 kg/m 2 ; n = 20) and a group with lower insulin resistance (L-IR, 35 ± 9 years; 27.8 ± 2.8 kg/m 2 ; n = 20). Anthropometric, cardiovascular, metabolic, and performance variables were measured at baseline and after 10 weeks of training. Results: There were significant training-induced changes [delta percent (Δ%)] in fasting glucose, fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) scores in the H-IR group (-8.8, -26.5, -32.1%, p performance co-variables after 10 weeks of HIIT in sedentary adult women. This research demonstrates the protective effect of HIIT against cardiometabolic disease progression in a sedentary population.

  20. Adipocyte LDL receptor–related protein–1 expression modulates postprandial lipid transport and glucose homeostasis in mice

    Science.gov (United States)

    Hofmann, Susanna M.; Zhou, Li; Perez-Tilve, Diego; Greer, Todd; Grant, Erin; Wancata, Lauren; Thomas, Andrew; Pfluger, Paul T.; Basford, Joshua E.; Gilham, Dean; Herz, Joachim; Tschöp, Matthias H.; Hui, David Y.

    2007-01-01

    Diet-induced obesity and its serious consequences such as diabetes, cardiovascular disease, and cancer are rapidly becoming a major global health threat. Therefore, understanding the cellular and molecular mechanisms by which dietary fat causes obesity and diabetes is of paramount importance in order to identify preventive and therapeutic strategies. Increased dietary fat intake results in high plasma levels of triglyceride-rich lipoproteins (TGRL). Tissue uptake of TGRL has been shown to promote glucose intolerance. We generated mice with an adipocyte-specific inactivation of the multifunctional receptor LDL receptor–related protein–1 (LRP1) to determine its role in mediating the effects of TGRL on diet-induced obesity and diabetes. Knockout mice displayed delayed postprandial lipid clearance, reduced body weight, smaller fat stores, lipid-depleted brown adipocytes, improved glucose tolerance, and elevated energy expenditure due to enhanced muscle thermogenesis. We further demonstrated that inactivation of adipocyte LRP1 resulted in resistance to dietary fat–induced obesity and glucose intolerance. These findings identify LRP1 as a critical regulator of adipocyte energy homeostasis, where functional disruption leads to reduced lipid transport, increased insulin sensitivity, and muscular energy expenditure. PMID:17948131

  1. High liver glycogen in hereditary fructose intolerance

    Science.gov (United States)

    Cain, A. R. R.; Ryman, Brenda E.

    1971-01-01

    A case of hereditary fructose intolerance is reported in a girl aged 2 years at the time of her death. She had apparently progressed normally until the age of 14 months. At 19 months she was admitted to hospital with failure to thrive, hepatomegaly, and superficial infections. Investigations revealed hypoglycaemia, persistent acidosis, aminoaciduria, and a high liver glycogen level which suggested that she had glycogen storage disease. There was also some evidence of malabsorption. At necropsy the liver enzyme estimations showed that fructose 1-phosphate aldolase activity was absent and that fructose 1,6-diphosphate aldolase activity was reduced. Hereditary fructose intolerance and glycogen storage disease have been confused in the past on clinical grounds, but a high liver glycogen level has not previously been reported in hereditary fructose intolerance. PMID:5289293

  2. Associations between Ultrasound Measures of Abdominal Fat Distribution and Indices of Glucose Metabolism in a Population at High Risk of Type 2 Diabetes: The ADDITION-PRO Study

    DEFF Research Database (Denmark)

    Philipsen, Annelotte; Jørgensen, Marit E; Vistisen, Dorte

    2015-01-01

    metabolism in a population at high risk of type 2 diabetes. METHODS: A cross-sectional analysis of 1342 participants of the ADDITION-PRO study. We measured visceral adipose tissue and subcutaneous adipose tissue with ultrasonography, anthropometrics and body fat percentage by bioelectrical impedance. Indices...... standard deviation difference in BMI, visceral adipose tissue, waist circumference, waist/height ratio and body fat percentage corresponded approximately to 0.2mmol/l higher fasting glucose, 0.7mmol/l higher 2-hr glucose, 0.06-0.1% higher HbA1c, 30 % lower HOMA index of insulin sensitivity, 20% lower Gutt......'s index of insulin sensitivity, and 100 unit higher Stumvoll's index of beta-cell function. After adjustment for waist circumference visceral adipose tissue was still significantly associated with glucose intolerance and insulin resistance, whereas there was a trend towards inverse or no associations...

  3. Red peppers with moderate and severe pungency prevent the memory deficit and hepatic insulin resistance in diabetic rats with Alzheimer's disease.

    Science.gov (United States)

    Yang, Hye Jeong; Kwon, Dae Young; Kim, Min Jung; Kang, Suna; Moon, Na Rang; Daily, James W; Park, Sunmin

    2015-01-01

    Dementia induced by β-amyloid accumulation impairs peripheral glucose homeostasis, but red pepper extract improves glucose homeostasis. We therefore evaluated whether long-term oral consumption of different red pepper extracts improves cognitive dysfunction and glucose homeostasis in type 2 diabetic rats with β-amyloid-induced dementia. Male diabetic rats received hippocampal CA1 infusions of β-amyloid (25-35) (AD) or β-amyloid (35-25, non-plaque forming), at a rate of 3.6 nmol/day for 14 days (Non-AD). AD rats were divided into four dietary groups receiving either 1% lyophilized 70% ethanol extracts of either low, moderate and severe pungency red peppers (AD-LP, AD-MP, and AD-SP) or 1% dextrin (AD-CON) in Western diets (43% energy as fat). The ascending order of control memory deficit measured by passive avoidance test and water maze test. Furthermore, the accumulation of β-amyloid induced glucose intolerance, although serum insulin levels were elevated during the late phase of oral glucose tolerance test (OGTT). All of the red pepper extracts prevented the glucose intolerance in AD rats. Consistent with OGTT results, during euglycemic hyperinulinemic clamp glucose infusion rates were lower in AD-CON than Non-AD-CON with no difference in whole body glucose uptake. Hepatic glucose output at the hyperinsulinemic state was increased in AD-CON. β-amyloid accumulation exacerbated hepatic insulin resistance, but all red pepper extract treatments reversed the insulin resistance in AD rats. The extracts of moderate and severe red peppers were found to prevent the memory deficit and exacerbation of insulin resistance by blocking tau phosphorylation and β-amyloid accumulation in diabetic rats with experimentally induced Alzheimer's-like dementia. These results suggest that red pepper consumption might be an effective intervention for preventing age-related memory deficit.

  4. The effects of whole grain high-amylose maize flour as a source of resistant starch on blood glucose, satiety, and food intake in young men.

    Science.gov (United States)

    Luhovyy, Bohdan L; Mollard, Rebecca C; Yurchenko, Svitlana; Nunez, Maria Fernanda; Berengut, Shari; Liu, Ting Ting; Smith, Christopher E; Pelkman, Christine L; Anderson, G Harvey

    2014-12-01

    The objective of this study was to determine the dose response effect of whole grain high-amylose maize (HAM) flour as a source of resistant starch (RS) on blood glucose, appetite and short-term food intake. In a repeated-measures crossover trial, healthy men (n = 30, 22.9 ± 0.6 y, BMI of 22.6 ± 0.3 kg/m(2)) were randomly assigned to consume 1 of 3 cookies once a week for 3 wk. Cookies were control (100% wheat flour), low-dose (63% wheat flour,37% HAM flour), and high-dose (33% wheat flour, 67% HAM flour) providing 53.5, 43.5, and 36.3 g of available carbohydrate, respectively. Ad libitum food intake was measured 120 min at a pizza meal, blood glucose and subjective appetite were measured after consumption of the cookie (0 to 120 min) and after the pizza meal (140 to 200 min). Blood glucose concentrations were lower at 30 and 45 min after high-dose treatment, and at 120 min after both high- and low-dose treatments compared to control (P flour as a source of RS and incorporated into a cookie was associated with better glycemic control in young men. © 2014 Institute of Food Technologists®

  5. Trehalose degradation and glucose efflux precede cell ejection during germination of heat-resistant ascospores of Talaromyces macrosporus

    NARCIS (Netherlands)

    Dijksterhuis, Jan; van Driel, Kenneth G A; Sanders, Mark G; Molenaar, Douwe; Houbraken, Jos A M P; Samson, Rob A; Kets, Edwin P W

    Talaromyces macrosporus forms ascospores that survive pasteurization treatments. Ascospores were dense (1.3 g ml(-1)), relatively dry [0.6 g H(2)O (g dry weight)(-1)] and packed with trehalose (9-17% fresh weight). Trehalose was degraded to glucose monomers between 30 and 100 min after heat

  6. Trehalose degradation and glucose efflux precede cell ejection during germination of heat-resistant acospores of Talaromyces macrosporus

    NARCIS (Netherlands)

    Dijksterhuis, J.; Driel, van K.G.A.; Sanders, M.G.; Molenaar, D.; Houbraken, J.A.M.P.; Samson, R.A.; Kets, E.P.W.

    2002-01-01

    Talaromyces macrosporus forms ascospores that survive pasteurization treatments. Ascospores were dense (1.3 g ml-1), relatively dry [0.6 g H2O (g dry weight)-1] and packed with trehalose (9-17␏resh weight). Trehalose was degraded to glucose monomers between 30 and 100 min after heat activation of

  7. The glycogen of Galdieria sulphuraria as alternative to starch for the production of slowly digestible and resistant glucose polymers

    NARCIS (Netherlands)

    Martinez-Garcia, Marta; Kormpa, Akrivi; van der Maarel, Marc J. E. C.

    2017-01-01

    Highly branched glucose polymers produced from starch are applied in various products, such as peritoneal dialysis solutions and sports drinks. Due to its insoluble, granular nature, the use of native starch as substrate requires an energy consuming pre-treatment to achieve solubilization at the

  8. Fasting glucose, fasting insulin, and insulin resistance in the prediction of myocardial infarction and mortality at long-term follow-up

    DEFF Research Database (Denmark)

    Nielsen, M. L.; Pareek, M.; Leosdottir, M.

    2015-01-01

    Objective: To assess the additional prognostic value of fasting blood glucose (FBG), fasting plasma insulin (FPI), and homeostasis model assessment derived insulin resistance (HOMA-IR) for predicting incident myocardial infarction (MI) and all-cause mortality, independently of traditional...... measured at baseline. Subsequently, HOMA-IR was derived using the computerized HOMA calculator and ranked into quartiles due to the non-normal distribution and presumably non-linear biological effect of insulin resistance. Prognostic values of FBG, FPI, HOMA-IR, and traditional risk factors were tested.......1-48.3] years, whereas median [IQR] HOMA-IR was 0.9 [0.4-1.4]. Over a median follow-up time of 20 years, 1448 events occurred (11.3 per 1000 person-years). The simple prediction model, i.e. the model with traditional CV risk factors only, included age, gender, body mass index, systolic blood pressure, total...

  9. Tyrosine Phosphorylation of the UDP-Glucose Dehydrogenase of Escherichia coli Is at the Crossroads of Colanic Acid Synthesis and Polymyxin Resistance

    DEFF Research Database (Denmark)

    Lacour, S.; Bechet, E.; Cozzone, A.J.

    2008-01-01

    to participate in the regulation of the amount of the exopolysaccharide colanic acid, whereas Etk-mediated Ugd phosphorylation appeared to participate in the resistance of E. coli to the antibiotic polymyxin. Conclusions/Significance: Ugd phosphorylation seems to be at the junction between two distinct...... shown to phosphorylate the UDP-glucose dehydrogenase Ugd in vitro. Not only is Ugd involved in the biosynthesis of extracellular polysaccharides, but also in the production of UDP-4-amino-4-deoxy-L-arabinose, a compound that renders E. coli resistant to cationic antimicrobial peptides. Methodology....../Principal Findings: Here, we studied the role of Ugd phosphorylation. We first confirmed in vivo the phosphorylation of Ugd by Wzc and we demonstrated that Ugd is also phosphorylated by Etk, the other BY-kinase identified in E. coli. Tyrosine 71 (Tyr71) was characterized as the Ugd site phosphorylated by both Wzc...

  10. The effect of long-term taurine supplementation and fructose feeding on glucose and lipid homeostasis in Wistar rats.

    Science.gov (United States)

    Larsen, Lea Hüche; Orstrup, Laura Kofoed Hvidsten; Hansen, Svend Høime; Grunnet, Niels; Quistorff, Bjørn; Mortensen, Ole Hartvig

    2013-01-01

    The nonprotein amino acid taurine has been shown to counteract the negative effects of a high-fructose diet in rats with regard to insulin resistance and dyslipidemia. Here we examined the long-term (26 weeks) effects of oral taurine supplementation (2% in the drinking water) in fructose-fed Wistar rats.The combination of fructose and taurine caused a significant increase in fasting glucose compared to the control diet without changing hepatic phosphoenol pyruvate carboxykinase mRNA levels. The combination of fructose and taurine also improved glucose tolerance compared to control. Neither a high-fructose diet nor taurine supplementation induced significant changes in body weight, body fat or total calorie intake, fasting insulin levels, HOMA-IR, or insulin-induced Akt phosphorylation in skeletal muscle.Fructose alone caused a decrease in liver triglyceride content, with taurine supplementation preventing this. There was no effect of long-term fructose diet and/or taurine supplementation on plasma triglycerides, plasma nonesterified fatty acids, as well as plasma HDL, LDL, and total cholesterol.In conclusion, the study suggests that long-term taurine supplementation improves glucose tolerance and normalize hepatic triglyceride content following long-term fructose feeding. However, as the combination of taurine and fructose also increased fasting glucose levels, the beneficial effect of taurine supplementation towards amelioration of glucose intolerance and insulin resistance may be questionable.

  11. Influence of castration-induced testosterone and estradiol deficiency on obesity and glucose metabolism in male Göttingen minipigs.

    Science.gov (United States)

    Christoffersen, Berit Oestergaard; Gade, Laust Peter; Golozoubova, Valeria; Svendsen, Ove; Raun, Kirsten

    2010-10-01

    Low testosterone and estradiol concentrations are predictive for the development of the metabolic syndrome in men and women, respectively. The aim of this study was to investigate the influence of sex hormone deficiency on food intake, body weight, body composition and glucose metabolism in male Göttingen minipigs. Five adult male Göttingen minipigs were studied before castration (pre-cast), 10-18 days (post-cast 1) and 10-11 weeks (post-cast 2) after castration. Parameters of interest were food intake, body weight, body fat percentage and sex hormone concentrations. Furthermore glucose tolerance, glucagon suppression, insulin resistance, beta cell function and disposition index were evaluated by oral and intravenous glucose tolerance tests. Castration led to almost complete disappearance of circulating testosterone and estradiol and secondarily to increased food intake, body weight and body fat percentage. Ten-eighteen days sex hormone deficiency (post-cast 1) did not significantly change any of the investigated metabolic parameters compared to pre-cast levels. Ten weeks after castration (post-cast 2) significant insulin resistance, glucose intolerance and hyperglucagonemia was found, and the beta cell function and the disposition index both were decreased. In conclusion, castration-induced sex hormone deficiency in male Göttingen minipigs results in hyperphagia, obesity and disturbed glucose metabolism, which are some of the features typical for the human metabolic syndrome.

  12. Adherence to the dietary approaches to stop hypertension trial (DASH) diet is inversely associated with incidence of insulin resistance in adults: the Tehran lipid and glucose study.

    Science.gov (United States)

    Esfandiari, Saeed; Bahadoran, Zahra; Mirmiran, Parvin; Tohidi, Maryam; Azizi, Fereidoun

    2017-09-01

    Beneficial effects of Dietary Approaches to Stop Hypertension trial (DASH) diet on features of metabolic syndrome have been indicated in clinical studies. In this study, we aimed to assess possible association of DASH diet score and the risk of insulin resistance in an Iranian population. In this prospective cohort study, 927 adult men and women, were recruited. Fasting serum insulin and glucose were measured at baseline and again after 3 years. Usual dietary intakes were measured using a validated 168 item semi-quantitative food frequency questionnaire and DASH score was calculated. Multivariate logistic regression models were used to estimate the occurrence of the insulin resistance across tertiles of DASH diet. To investigate possible superiority of DASH score over other scoring system, we also assessed the association of healthy eating index and Mediterranean diet score with the risk of insulin resistance. Mean age of the participants was 40.34 ± 12.14 years old. The incidence rate of insulin resistance was 12.8%. Participants with higher DASH score had also higher intakes of potassium, calcium, magnesium, fiber, and lower intakes of cholesterol ( p DASH score and the risk insulin resistance in the highest compared to the lowest tertile (OR = 0.39, 95% CI = 0.20-0.76, p for trend = 0.007). There was no significant association between healthy eating index and Mediterranean diet score with the incidence of insulin resistance. In conclusion, adherence to the DASH dietary pattern may be associated with a lower risk of insulin resistance and its related metabolic outcomes.

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

    Science.gov (United States)

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

    2014-01-01

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

  14. [An epidemiological study of food intolerance in 2434 children].

    Science.gov (United States)

    Liu, Xiao-Juan; Zhu, Ting-Ting; Zeng, Rong; Chang, Li; Li, Feng-Yi; Li, Wen-Sheng; Jiang, Yong-Mei

    2013-07-01

    To investigate the epidemiological characteristics of intolerance to 14 foods in children and the relationship between food intolerance and disease of various systems. Serum samples of 2434 children with diseases were collected for food intolerance testing between January 2009 and October 2012. Allergen-specific IgG antibodies to 14 foods were detected using enzyme-linked immunosorbent assay. The children's intolerance to different foods and its relationship with age, sex and disease of various systems were analyzed. Among these children, positive rates of intolerance to milk and eggs were as high as 74.16% and 66.47% respectively, while positive rates of intolerance to chicken and pork were relatively low (0.29% and 0.21% respectively). The overall positive rates of food intolerance were 12.579% and 12.470% in males and females respectively. For infants, the highest intolerance rate was to milk; for preschool and school-age children, the highest intolerance rates were to milk and eggs respectively; for children in adolescence, the highest intolerance rate was to eggs. Among children with food intolerance involving single system, those with developmental abnormality or immune system disease had the highest overall positive rate of food intolerance. Children with double-system diseases had an overall positive rate of food intolerance as high as 13.393%. Among the children involving various systems, the positive rate of intolerance to milk and eggs were higher than other food. Factors influencing food intolerance in children include food categories and age. There may be a relationship between food intolerance and disease of various systems, and this is significant to the growth and development of children.

  15. Debates in allergy medicine: food intolerance does not exist

    OpenAIRE

    Dreborg, Sten

    2015-01-01

    BACKGROUND: The term "intolerance" is not mentioned in the World Allergy Organization (WAO) document on allergy nomenclature. "Intolerance" has been used to describe some non-immunological diseases. However, pediatric gastroenterologists mix allergy and intolerance, e.g. by using the term "cow's milk protein allergy/intolerance (CMPA/I)", lumping together all types of mechanisms for not tolerating cow's milk. The basis for this mix is the fact that double-blind oral food challenges are time-c...

  16. Lactase persistence versus lactose intolerance: Is there an intermediate phenotype?

    Science.gov (United States)

    Dzialanski, Zbigniew; Barany, Michael; Engfeldt, Peter; Magnuson, Anders; Olsson, Lovisa A; Nilsson, Torbjörn K

    2016-02-01

    According to the prevailing theory about the genetic background to lactose intolerance, there are three genotypes but only two adult physiological phenotypes: lactase persistence in individuals with the CT and TT genotypes and lactase non-persistence in individuals with the CC genotype. However, analysis of lactase activity from intestinal biopsies has revealed three distinct levels of activity, suggesting that an intermediate physiological phenotype may exist. To assess possible disparities between different genotypes with regard to biomarkers of lactase activity and physical symptoms during an oral lactose load test. A retrospective study using an oral lactose load test (n=487). Concentrations of hydrogen in exhaled air and blood glucose were measured. Afterwards, subjects were asked to provide oral mucosa samples for genotyping and answer a questionnaire (participation rate 56%, n=274). Mean hydrogen levels in exhaled air at 120min were significantly higher in the CT genotype than in the TT genotype. There was no significant difference in blood glucose levels between the two groups. Reported symptoms, with the possible exception of abdominal pain, were equally prevalent in both groups. Subjects with the CT and TT genotypes, hitherto classified as lactase-persistent, differ in their physiological response to lactose intake, indicating differences in phenotype which could have clinical significance. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  17. Free fatty acid-induced hepatic insulin resistance is attenuated following lifestyle intervention in obese individuals with impaired glucose tolerance

    DEFF Research Database (Denmark)

    Haus, Jacob M; Solomon, Thomas; Marchetti, Christine M

    2010-01-01

    The objective of the study was to examine the effects of an exercise/diet lifestyle intervention on free fatty acid (FFA)-induced hepatic insulin resistance in obese humans.......The objective of the study was to examine the effects of an exercise/diet lifestyle intervention on free fatty acid (FFA)-induced hepatic insulin resistance in obese humans....

  18. Comparison of different definitions of feeding intolerance

    DEFF Research Database (Denmark)

    Reintam Blaser, Annika; Starkopf, Liis; Deane, Adam M

    2015-01-01

    BACKGROUND & AIMS: While feeding intolerance (FI) is clinically important in the critically ill it is inconsistently defined. By evaluating definitions of FI based on relationships between symptoms and signs of gastrointestinal (GI) dysfunction and mortality the objective was to define FI using...

  19. Milk Intolerance, Beta-Casein and Lactose.

    Science.gov (United States)

    Pal, Sebely; Woodford, Keith; Kukuljan, Sonja; Ho, Suleen

    2015-08-31

    True lactose intolerance (symptoms stemming from lactose malabsorption) is less common than is widely perceived, and should be viewed as just one potential cause of cows' milk intolerance. There is increasing evidence that A1 beta-casein, a protein produced by a major proportion of European-origin cattle but not purebred Asian or African cattle, is also associated with cows' milk intolerance. In humans, digestion of bovine A1 beta-casein, but not the alternative A2 beta-casein, releases beta-casomorphin-7, which activates μ-opioid receptors expressed throughout the gastrointestinal tract and body. Studies in rodents show that milk containing A1 beta-casein significantly increases gastrointestinal transit time, production of dipeptidyl peptidase-4 and the inflammatory marker myeloperoxidase compared with milk containing A2 beta-casein. Co-administration of the opioid receptor antagonist naloxone blocks the myeloperoxidase and gastrointestinal motility effects, indicating opioid signaling pathway involvement. In humans, a double-blind, randomized cross-over study showed that participants consuming A1 beta-casein type cows' milk experienced statistically significantly higher Bristol stool values compared with those receiving A2 beta-casein milk. Additionally, a statistically significant positive association between abdominal pain and stool consistency was observed when participants consumed the A1 but not the A2 diet. Further studies of the role of A1 beta-casein in milk intolerance are needed.

  20. Chemical Intolerance among Hairdressers in Denmark

    DEFF Research Database (Denmark)

    Tran, Marie Thi Dao; Elberling, Jesper; Skovbjerg, Sine

    2013-01-01

    To investigate the prevalence and the severity of fragrance-related symptoms among hairdressers in Denmark compared with the Danish general population. Further, to characterize former hairdressers who are severely chemically intolerant to fragranced products in relation to sex, age and health...

  1. Intolerance of Uncertainty and Adult Separation Anxiety

    NARCIS (Netherlands)

    Boelen, Paul A.; Reijntjes, Albert; Carleton, R. Nicholas

    2014-01-01

    Intolerance of uncertainty (IU)—the tendency to react negatively to situations that are uncertain—is involved in different anxiety disorders and depression. No studies have yet examined the association between IU and symptoms of adult separation anxiety disorder. However, it is possible that greater

  2. Intolerance to dietary biogenic amines : a review

    NARCIS (Netherlands)

    Jansen, SC; van Dusseldorp, M; Bottema, KC; Dubois, AEJ

    Objective: To evaluate the scientific evidence for purported intolerance to dietary biogenic amines. Data Sources: MEDLINE was searched for articles in the English language published between January 1966 and August 2001. The keyword biogenic amin* was combined with hypersens*, allergen intoler*, and

  3. [Food allergy, food intolerance or functional disorder?].

    Science.gov (United States)

    Wüthrich, B

    2009-04-01

    The term "food allergy" is widely misused for all sorts of symptoms and diseases caused by food. Food allergy (FA) is an adverse reaction to food (food hypersensitivity) occurring in susceptible individuals, which is mediated by a classical immune mechanism specific for the food itself. The best established mechanism in FA is due to the presence of IgE antibodies against the offending food. Food intolerance (FI) are all non-immune-mediated adverse reactions to food. The subgroups of FI are enzymatic (e.g. lactose intolerance due to lactase deficiency), pharmacological (reactions against biogenic amines, histamine intolerance), and undefined food intolerance (e.g. against some food additives). The diagnosis of an IgE-mediated FA is made by a carefully taken case history, supported by the demonstration of an IgE sensitization either by skin prick tests or by in vitro tests, and confirmed by positive oral provocation. For scientific purposes the only accepted test for the confirmation of FA/FI is a properly performed double-blind, placebo-controlled food challenge (DBPCFC). A panel of recombinant allergens, produced as single allergenic molecules, may in future improve the diagnosis of IgE-mediated FA. Due to a lack of causal treatment possibilities, the elimination of the culprit "food allergen" from the diet is the only therapeutic option for patients with real food allergy.

  4. Lactose intolerance and cow's milk protein allergy

    Directory of Open Access Journals (Sweden)

    Adriano Henrique do Nascimento RANGEL

    2016-01-01

    Full Text Available Abstract Adverse reactions to food intake have very diverse etiology and symptomatology. Regarding milk, its food allergy is presented as lactose intolerance, the sugar in milk, or allergy to milk protein. Despite having different symptomatology, confusions among allergic conditions to dairy and its mediators are common. Milk protein allergy originates from protein components present in milk, causing reactions to either the protein fractions in emulsion (caseins or in whey (milk albumin. The allergic reaction is type IV mediated by T lymphocytes. The allergic reaction produces severe cellular damage and it triggers physical, mental and emotional symptomatology that may vary in time, intensity and severity. Lactose intolerance is originated by total or partial absence of the enzyme that digests this disaccharide. Lactose intolerance can be primary or congenital and secondary; the former being more rare and severe, the latter being more common. Lactase deficiency can be diagnosed by symptoms associated with cramping and diarrhea. Thus, the objective of this study was to conduct a review of available literature on cow’s milk protein allergy and lactose intolerance.

  5. [Lactose intolerance: past and present. Part II].

    Science.gov (United States)

    Buzás, György Miklós

    2015-10-25

    The author summarises the interrelations between lactose intolerance, calcium and vitamin D metabolism and osteoporosis. Lactose intolerance enhances the risk of forearm and hip fractures in some patients. Lactase gene genotype and fracture risk are related in some populations. Calcium and vitamin D supplementation increase bone mineral content and they are justified in children, during pregnancy and lactation, and in postmenopausal women. The intake of milk and milk products could increase the risk of ovarian carcinoma. CC genotype of the lactase gene increased the risk of colorectal carcinoma in Finns; no such effect was observed in British, Spanish and Italian patients. Even small quantities of lactose in drugs (10-750 mg) could elicit intolerance symptoms due to individual susceptibility. In spite of public knowledge and advertising, controlled studies did not prove the beneficial effect of either a lactose-free diet, enzyme supplementation or probiotics in an evidence-based manner. While accepted guidelines are lacking, a personalised therapy is mandatory. In spite of increasing public interest in lactose intolerance, many unknown factors must still be studied.

  6. Lactose intolerance : the role of colonic metabolism

    NARCIS (Netherlands)

    He, Tao

    2006-01-01

    Dairy products provide us with calcium and other valuable nutrients. However, they also contain lactose which is maldigested by a large part of the world adult population. The mechanisms by which lactose maldigestion causes symptoms of lactose intolerance are not fully understood. Studies on the

  7. Intolerance to dietary biogenic amines: A review

    NARCIS (Netherlands)

    Jansen, S.C.; Dusseldorp, M. van; Bottema, K.C.; Dubois, A.E.J.

    2003-01-01

    Objective: To evaluate the scientific evidence for purported intolerance to dietary biogenic amines. Data Sources: MEDLINE was searched for articles in the English language published between January 1966 and August 2001. The keyword biogenic amin* was combined with hypersens*, allerg*, intoler*, and

  8. Fear of heights and visual height intolerance.

    Science.gov (United States)

    Brandt, Thomas; Huppert, Doreen

    2014-02-01

    The aim of this review is, first, to cover the different aspects of visual height intolerance such as historical descriptions, definition of terms, phenomenology of the condition, neurophysiological control of gaze, stance and locomotion, and therapy, and, second, to identify warranted epidemiological and experimental studies. Vivid descriptions of fear of heights can be found in ancient texts from the Greek, Roman, and Chinese classics. The life-time prevalence of visual height intolerance is as high as 28% in the general population, and about 50% of those who are susceptible report an impact on quality of life. When exposed to heights, visual exploration by eye and head movements is restricted, and the velocity of locomotion is reduced. Therapy for fear of heights is dominated by the behavioral techniques applied during real or virtual reality exposure. Their efficacy might be facilitated by the administration of D-cycloserine or glucocorticoids. Visual height intolerance has a considerable impact on daily life and interpersonal interactions. It is much more frequent than fear of heights, which is defined as an environmental subtype of a specific phobia. There is certainly a continuum stretching from acrophobia to a less-pronounced visual height intolerance, to which the categorical distinction of a specific phobia does not apply.

  9. Lactose intolerance : analysis of underlying factors

    NARCIS (Netherlands)

    Vonk, RJ; Priebe, MG; Koetse, HA; Stellaard, F; Lenoir-Wijnkoop, [No Value; Antoine, JM; Zhong, Y; Huang, CY

    Background We studied the degree of lactose digestion and orocecal transit time (OCTT) as possible causes for the variability of symptoms of lactose intolerance (LI) in a sample of a population with genetically determined low lactase activity. Methods Lactose digestion index (LDI) was measured by

  10. Severe lactose intolerance with lactosuria and vomiting.

    Science.gov (United States)

    Hosková, A; Sabacký, J; Mrskos, A; Pospísil, R

    1980-01-01

    An infant with lactose intolerance is described. A breast-fed infant developed vomiting at 3 weeks, and became dehydrated. Lactosuria, aminoaciduria, and liver damage were preesent. A milk-free diet led to rapid recovery. At 6 months a normal diet was well tolerated. PMID:7416780

  11. Milk Intolerance, Beta-Casein and Lactose

    Directory of Open Access Journals (Sweden)

    Sebely Pal

    2015-08-01

    Full Text Available True lactose intolerance (symptoms stemming from lactose malabsorption is less common than is widely perceived, and should be viewed as just one potential cause of cows’ milk intolerance. There is increasing evidence that A1 beta-casein, a protein produced by a major proportion of European-origin cattle but not purebred Asian or African cattle, is also associated with cows’ milk intolerance. In humans, digestion of bovine A1 beta-casein, but not the alternative A2 beta-casein, releases beta-casomorphin-7, which activates μ-opioid receptors expressed throughout the gastrointestinal tract and body. Studies in rodents show that milk containing A1 beta-casein significantly increases gastrointestinal transit time, production of dipeptidyl peptidase-4 and the inflammatory marker myeloperoxidase compared with milk containing A2 beta-casein. Co-administration of the opioid receptor antagonist naloxone blocks the myeloperoxidase and gastrointestinal motility effects, indicating opioid signaling pathway involvement. In humans, a double-blind, randomized cross-over study showed that participants consuming A1 beta-casein type cows’ milk experienced statistically significantly higher Bristol stool values compared with those receiving A2 beta-casein milk. Additionally, a statistically significant positive association between abdominal pain and stool consistency was observed when participants consumed the A1 but not the A2 diet. Further studies of the role of A1 beta-casein in milk intolerance are needed.

  12. Identifying Foods causing Allergies/ Intolerances among Diabetic ...

    African Journals Online (AJOL)

    Objective: This study was designed to identify the foods that caused allergies / intolerances and symptoms of reaction experienced by diabetic patients attending State Specialist Hospital, Akure. Materials and Methods: Ninety-eight diabetics aged 30-80 years (30 males and 68 females) were included in the study.

  13. Dermatitis herpetiformis intolerant to dapsone in Aids

    Directory of Open Access Journals (Sweden)

    Krishna K

    1999-01-01

    Full Text Available A 35-year-old man with AIDS and pulmonary tuberculosis presented with lesions suggestive of dermatitis herpetiformis and intolerance to dapsone. He was managed successfully with a combination of nicotinamide 200 mg/day and indomethacin 75 mg/day, topical steroids and gluten free diet.

  14. The Common C49620T Polymorphism in the Sulfonylurea Receptor Gene SUR1 (ABCC8) in Patients with Gestational Diabetes and Subsequent Glucose Metabolism Abnormalities

    Science.gov (United States)

    Molęda, Piotr; Bińczak-Kuleta, Agnieszka; Homa, Katarzyna; Safranow, Krzysztof; Celewicz, Zbigniew; Syrenicz, Anhelli; Stefański, Adam; Fronczyk, Aneta; Majkowska, Lilianna

    2012-01-01

    Aim. The aim of this study is to investigate the relationship between the common C49620T polymorphism in the sulfonylurea receptor (SUR1) gene and glucose metabolism, β-cell secretory function and insulin resistance in women with a history of gestational diabetes (GDM). Material and Methods. Study group included 199 women, diagnosed GDM within the last 5–12 years and control group of comparable 50 women in whom GDM was excluded during pregnancy. Blood glucose and insulin levels were measured during oral glucose tolerance test. Indices of insulin resistance (HOMA-IR) and β-cell function (HOMA %B) were calculated. In all patients, the C49620T polymorphism in intron 15 of the SUR1 gene was determined. Results. The distribution of the studied polymorphism in the two groups did not differ from each other (χ 2 = 0.34, P = 0.8425). No association between the distribution of polymorphisms and coexisting glucose metabolism disorders (χ 2 = 7,13, P = 0, 3043) was found. No association was also observed between the polymorphism and HOMA %B or HOMA-IR. Conclusions. The polymorphism C49620T in the SUR1 gene is not associated with insulin resistance and/or insulin secretion in women with a history of GDM and does not affect the development of GDM, or the development of glucose intolerance in the studied population. PMID:22927833

  15. Acylated apelin-13 amide analogues exhibit enzyme resistance and prolonged insulin releasing, glucose lowering and anorexic properties.

    Science.gov (United States)

    O'Harte, Finbarr P M; Parthsarathy, Vadivel; Hogg, Christopher; Flatt, Peter R

    2017-12-15

    The adipokine, apelin has many biological functions but its activity is curtailed by rapid plasma degradation. Fatty acid derived apelin analogues represent a new and exciting avenue for the treatment of obesity-diabetes. This study explores four novel fatty acid modified apelin-13 analogues, namely, (Lys 8 GluPAL)apelin-13 amide, pGlu(Lys 8 GluPAL)apelin-13 amide, Lys 8 GluPAL(Tyr 13 )apelin-13 and Lys 8 GluPAL(Val 13 )apelin-13. Fatty acid modification extended the half-life of native apelin-13 to >24 h in vitro. pGlu(Lys 8 GluPAL)apelin-13 amide was the most potent insulinotropic analogue in BRIN-BD11 cells and isolated islets with maximal stimulatory effects of up to 2.7-fold (p glucose uptake in 3T3-L1 adipocytes (2.3-fold, p glucose (39-43%, p glucose tolerance tests in diet-induced obese mice. pGlu(Lys 8 GluPAL)apelin-13 amide and (Lys 8 GluPAL)apelin-13 amide also inhibited feeding (28-40%, p < .001), whereas Lys 8 GluPAL(Val 13 )apelin-13 increased food intake (8%, p < .05) in mice. These data indicate that novel enzymatically stable analogues of apelin-13 may be suitable for future development as therapeutic agents for obesity-diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Prevalence of Non-responders for Glucose Control Markers after 10 Weeks of High-Intensity Interval Training in Adult Women with Higher and Lower Insulin Resistance

    Science.gov (United States)

    Álvarez, Cristian; Ramírez-Campillo, Rodrigo; Ramírez-Vélez, Robinson; Izquierdo, Mikel

    2017-01-01

    Background: Exercise training improves performance and biochemical parameters on average, but wide interindividual variability exists, with individuals classified as responders (R) or non-responders (NRs), especially between populations with higher or lower levels of insulin resistance. This study assessed the effects of high-intensity interval training (HIIT) and the prevalence of NRs in adult women with higher and lower levels of insulin resistance. Methods: Forty adult women were assigned to a HIIT program, and after training were analyzed in two groups; a group with higher insulin resistance (H-IR, 40 ± 6 years; BMI: 29.5 ± 3.7 kg/m2; n = 20) and a group with lower insulin resistance (L-IR, 35 ± 9 years; 27.8 ± 2.8 kg/m2; n = 20). Anthropometric, cardiovascular, metabolic, and performance variables were measured at baseline and after 10 weeks of training. Results: There were significant training-induced changes [delta percent (Δ%)] in fasting glucose, fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) scores in the H-IR group (−8.8, −26.5, −32.1%, p HOMA-IR (25 vs. 45%, p = 0.185). Conclusion: Independent of the “magnitude” of the cardiometabolic disease (i.e., higher vs. lower insulin resistance), no differences were observed in the NRs prevalence with regard to improved HOMA-IR or to anthropometric, cardiovascular, and muscle performance co-variables after 10 weeks of HIIT in sedentary adult women. This research demonstrates the protective effect of HIIT against cardiometabolic disease progression in a sedentary population. PMID:28729841

  17. Relative contributions of energy expenditure on physical activity, body composition and weight gain to the evolution of impaired glucose tolerance to Frank diabetes. Highlights and achievements

    International Nuclear Information System (INIS)

    Adeyemo, A.A.

    2002-01-01

    The effect of obesity on glucose intolerance is a mixture of the impact of body composition on glucose-insulin relationships as well as the modulation of this metabolism by physical activity. Populations of the African diaspora in the Caribbean and the United States have higher levels of obesity, glucose intolerance and diabetes than the ancestral population in West Africa. This is most likely a consequence of lifestyle changes, including an apparent decline in physical activity and dietary changes

  18. Prevalence and Symptom Correlation of Lactose Intolerance in the North East Part of Bangladesh.

    Science.gov (United States)

    Saha, M; Shil, B C; Saha, S K; Chowdhury, M; Perveen, I; Banik, R; Rahman, M H

    2016-01-01

    This study was designed to see the prevalence of lactose intolerance and symptom correlation following oral lactose challenge in healthy volunteers in the north east part of Bangladesh. Symptoms of abdominal pain, nausea, borborygmi, flatulence, diarrhea and others were noted for 24 hours and blood glucose was estimated at 0 hour and 30 minutes after 50 gm oral lactose load to healthy volunteers. Failure to rise blood glucose level ≥1.1 mmol/l at 30 minutes after lactose intake from fasting level was taken as lactose malabsorption (LM) i.e., lactose intolerance. Sensitivity and specificity of different symptoms were then found out. A total of 171 volunteers (male 123, female 48) with a mean age 34.08 years participated in this study. Lactose intolerance was found among 82.5% (n=141, M=100, F=41) subjects. Symptoms mostly experience by the lactose malabsorbers were diarrhea 93(66.0%), borborygmi 80(56.7%), abdominal pain 31(22.0%) and flatulence 32(22.7%). LM prevalence was found to increase with increasing number of symptoms up to 3 symptoms. A week positive correlation (r=0.205, P=0.007) was found between the number of symptoms and proportion of subjects having positive lactose tolerance test. Lactose intolerance among healthy adults of North East part of our country is as common as in other Asian countries including China and Malaysia. But LM is higher than that of Europeans and south Indians. Diarrhea and borborygmi were mostly associated with LM.

  19. Clinical evaluation, biochemistry and genetic polymorphism analysis for the diagnosis of lactose intolerance in a population from northeastern Brazil

    Science.gov (United States)

    Ponte, Paulo Roberto Lins; de Medeiros, Pedro Henrique Quintela Soares; Havt, Alexandre; Caetano, Joselany Afio; Cid, David A C; de Moura Gondim Prata, Mara; Soares, Alberto Melo; Guerrant, Richard L; Mychaleckyj, Josyf; Lima, Aldo Ângelo Moreira

    2016-01-01

    OBJECTIVE: This work aimed to evaluate and correlate symptoms, biochemical blood test results and single nucleotide polymorphisms for lactose intolerance diagnosis. METHOD: A cross-sectional study was conducted in Fortaleza, Ceará, Brazil, with a total of 119 patients, 54 of whom were lactose intolerant. Clinical evaluation and biochemical blood tests were conducted after lactose ingestion and blood samples were collected for genotyping evaluation. In particular, the single nucleotide polymorphisms C>T-13910 and G>A-22018 were analyzed by restriction fragment length polymorphism/polymerase chain reaction and validated by DNA sequencing. RESULTS: Lactose-intolerant patients presented with more symptoms of flatulence (81.4%), bloating (68.5%), borborygmus (59.3%) and diarrhea (46.3%) compared with non-lactose-intolerant patients (plactose-tolerant phenotype (plactose, we found that the most effective cutoff for glucose levels obtained for lactose malabsorbers was T-13910 and G>A-22018) with lactose tolerance in this population and suggest clinical management for patients with lactose intolerance that considers single nucleotide polymorphism detection and a change in the biochemical blood test cutoff from <25 mg/dL to <15 mg/dL. PMID:26934237

  20. Clinical evaluation, biochemistry and genetic polymorphism analysis for the diagnosis of lactose intolerance in a population from northeastern Brazil.

    Science.gov (United States)

    Ponte, Paulo Roberto Lins; de Medeiros, Pedro Henrique Quintela Soares; Havt, Alexandre; Caetano, Joselany Afio; Cid, David A C; Prata, Mara de Moura Gondim; Soares, Alberto Melo; Guerrant, Richard L; Mychaleckyj, Josyf; Lima, Aldo Ângelo Moreira

    2016-02-01

    This work aimed to evaluate and correlate symptoms, biochemical blood test results and single nucleotide polymorphisms for lactose intolerance diagnosis. A cross-sectional study was conducted in Fortaleza, Ceará, Brazil, with a total of 119 patients, 54 of whom were lactose intolerant. Clinical evaluation and biochemical blood tests were conducted after lactose ingestion and blood samples were collected for genotyping evaluation. In particular, the single nucleotide polymorphisms C>T-13910 and G>A-22018 were analyzed by restriction fragment length polymorphism/polymerase chain reaction and validated by DNA sequencing. Lactose-intolerant patients presented with more symptoms of flatulence (81.4%), bloating (68.5%), borborygmus (59.3%) and diarrhea (46.3%) compared with non-lactose-intolerant patients (plactose-tolerant phenotype (plactose, we found that the most effective cutoff for glucose levels obtained for lactose malabsorbers was T-13910 and G>A-22018) with lactose tolerance in this population and suggest clinical management for patients with lactose intolerance that considers single nucleotide polymorphism detection and a change in the biochemical blood test cutoff from <25 mg/dL to <15 mg/dL.

  1. Distress intolerance and clinical functioning in persons with schizophrenia

    Science.gov (United States)

    Nugent, Katie L.; Chiappelli, Joshua; Rowland, Laura M.; Daughters, Stacey B.; Hong, L. Elliot

    2014-01-01

    Impaired tolerance to distress may help explain part of the cognitive and functional impairments in schizophrenia. This project investigated distress intolerance in schizophrenia patients (SZ) as compared to controls, and whether distress intolerance represented an independent domain in relationship to symptoms, cognition, and functional capacity. Healthy controls (n=43) and SZ (n=65) completed a psychological distress challenge experiment and their levels of intolerance to distress were estimated. SZ showed increased distress intolerance such that they were significantly more likely to terminate the distress challenge session early compared to controls. Greater distress intolerance was associated with reduced functional capacity and worse cognitive performance in SZ. Mediation analyses suggested that distress intolerance had an independent effect on functional capacity, while some of this effect was mediated by cognitive performance. Our results suggest that distress intolerance is a promising domain for treatment research, and functional capacity may be improved by targeting treatments towards SZ patient’s ability to tolerate distress. PMID:25107316

  2. The consequences of social intolerance on non-violent protest

    DEFF Research Database (Denmark)

    Rapp, Carolin; Ackermann, Kathrin

    2016-01-01

    This paper scrutinizes the impact of intolerance toward diverse ethnic, religious, and cultural groups on an individual's willingness to actively engage in non-violent protest. Following new insights, we examine the individual as well as the ecological effect of social intolerance on protest...... behavior. Drawing from insights of social psychology and communication science, we expect that the prevalence of intolerance reinforces the positive effect of individual-level intolerance on protest participation. From a rational choice perspective, however, a negative moderating effect is expected......, as the expression of opinions becomes redundant for intolerant individuals in an intolerant society. We base our multilevel analyses on data from the World Values Surveys covering 32 established democracies. Our results reveal that intolerance leads to more non-violent protest participation. This relationship...

  3. The Negative Influence of High-Glucose Ambience on Neurogenesis in Developing Quail Embryos

    OpenAIRE

    Chen, Yao; Fan, Jian-xia; Zhang, Zhao-long; Wang, Guang; Cheng, Xin; Chuai, Manli; Lee, Kenneth Ka Ho; Yang, Xuesong

    2013-01-01

    Gestational diabetes is defined as glucose intolerance during pregnancy and it is presented as high blood glucose levels during the onset pregnancy. This condition has an adverse impact on fetal development but the mechanism involved is still not fully understood. In this study, we investigated the effects of high glucose on the developing quail embryo, especially its impact on the development of the nervous system. We established that high glucose altered the central nervous system mophologi...

  4. Glucose Sensing

    CERN Document Server

    Geddes, Chris D

    2006-01-01

    Topics in Fluorescence Spectroscopy, Glucose Sensing is the eleventh volume in the popular series Topics in Fluorescence Spectroscopy, edited by Drs. Chris D. Geddes and Joseph R. Lakowicz. This volume incorporates authoritative analytical fluorescence-based glucose sensing reviews specialized enough to be attractive to professional researchers, yet also appealing to the wider audience of scientists in related disciplines of fluorescence. Glucose Sensing is an essential reference for any lab working in the analytical fluorescence glucose sensing field. All academics, bench scientists, and industry professionals wishing to take advantage of the latest and greatest in the continuously emerging field of glucose sensing, and diabetes care & management, will find this volume an invaluable resource. Topics in Fluorescence Spectroscopy Volume 11, Glucose Sensing Chapters include: Implantable Sensors for Interstitial Fluid Smart Tattoo Glucose Sensors Optical Enzyme-based Glucose Biosensors Plasmonic Glucose Sens...

  5. Resistant starch intake at breakfast affects postprandial responses in type 2 diabetics and enhances the glucose-dependent insulinotropic polypeptide--insulin relationship following a second meal.

    Science.gov (United States)

    MacNeil, Stacey; Rebry, Rachel M; Tetlow, Ian J; Emes, Michael J; McKeown, Bruce; Graham, Terry E

    2013-12-01

    Resistant starch (RS) consumption can modulate postprandial metabolic responses, but its effects on carbohydrate (CHO) handling in type 2 diabetics (T2D) are unclear. It was hypothesized that a bagel high in RS would improve glucose and insulin homeostasis following the 1st meal, regardless of the amount of available CHO, and that in association with incretins, the effects would carry over to a 2nd meal. Using a randomized crossover design, 12 T2D ingested four different bagel treatments (their 1st meal) determined by available CHO and the weight or amount of bagel consumed: treatment A, without RS (50 g of available CHO); treatment B, with RS (same total CHO as in A); treatment C, with RS (same available CHO as in A); and treatment D, with the same RS as in B and available CHO as in A and C. A standard 2nd meal was ingested 3 h later. Following the first meal, B elicited a lower glucose incremental area under the curve (iAUC) than C (P portion of the available CHO, while ingesting more RS influenced the GIP-insulin axis following the 2nd meal.

  6. Comparison of the effects on insulin resistance and glucose tolerance of 6-mo high-monounsaturated-fat, low-fat, and control diets

    DEFF Research Database (Denmark)

    Due, Anette; Larsen, Thomas M; Hermansen, Kjeld

    2008-01-01

    and after the 6-mo dietary intervention. All foods were provided by a purpose-built supermarket. RESULTS: After 6 mo, the MUFA diet reduced fasting glucose (-3.0%), insulin (-9.4%), and the homeostasis model assessment of insulin resistance score (-12.1%). Compared with the MUFA diet, the control diet...... loss. DESIGN: Forty-six nondiabetic, obese [mean (+/-SEM) body mass index (in kg/m(2)): 31.2 +/- 0.3] men (n = 20) and premenopausal women (n = 26) aged 28.0 +/- 0.7 y were randomly assigned to 1 of 3 diets after > or = 8% weight loss: 1) MUFA diet (n = 16): moderate in fat (35-45% of energy) and high...

  7. Differential effects of glucagon-like peptide-1 on microvascular recruitment and glucose metabolism in short- and long-term Insulin resistance

    DEFF Research Database (Denmark)

    Sjøberg, Kim Anker; Rattigan, Stephen; Jeppesen, Jacob Fuglsbjerg

    2015-01-01

    Acute infusion of glucagon-like-peptide-1 (GLP-1) has potent effects on blood flow distribution through the microcirculation in healthy humans and rats. High fat diet induces impairments in insulin-mediated microvascular recruitment (MVR) and muscle glucose uptake, and here we examined whether...... this could be reversed by GLP-1. Using contrast-enhanced ultrasound, microvascular recruitment was assessed by continuous real-time imaging of gas-filled microbubbles in the microcirculation after acute (5 days) and prolonged (8 weeks) high fat diet (HF) induced insulin resistance in rats. An euglycemic...... hyperinsulinemic clamp (3 mU·min(-1) ·kg(-1) ) with or without a co-infusion of GLP-1 (100 pmol·l(-1) ) was performed in anaesthetized rats. Consumption of the HF diet attenuated the insulin-mediated MVR in both 5 days and 8 weeks HF interventions which was associated with a 50% reduction in insulin...

  8. Intolerance to food additives - does it exist?

    Science.gov (United States)

    Turner, Paul J; Kemp, Andrew S

    2012-02-01

    'Food intolerance' is often confused with a range of adverse symptoms which may be coincidental to ingestion of food. 'Food intolerance' is defined as a reaction in which symptoms must be objectively reproducible and not known to involve an immunological mechanism. A more precise term is non-allergic food hypersensitivity, which contrasts with food allergies which are due to an immunological mechanism. Some children will experience food reactions to food additives. Reported symptoms range from urticaria/angioedema to hyperactive behaviours. While parents/carers report that over one fifth of children experience of food reaction, only 1 in 20 of these are confirmed to have a non-allergic food hypersensitivity on testing. © 2010 The Authors. Journal of Paediatrics and Child Health © 2010 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

  9. Orthostatic intolerance: a disorder of young women

    Science.gov (United States)

    Ali, Y. S.; Daamen, N.; Jacob, G.; Jordan, J.; Shannon, J. R.; Biaggioni, I.; Robertson, D.

    2000-01-01

    Orthostatic intolerance (OI) is a cause of significant disability in otherwise healthy women seen by gynecologists. Orthostatic tachycardia is often the most obvious hemodynamic abnormality found in OI patients, but symptoms may include dizziness, visual changes, discomfort in the head or neck, poor concentration, fatigue, palpitations, tremulousness, anxiety, and, in some cases, fainting (syncope). It is the most common disorder of blood pressure regulation after essential hypertension, and patients with OI are traditionally women of childbearing age. Estimates suggest that at least 500,000 Americans suffer from some form of OI, and such patients comprise the largest group referred to centers specialized in autonomic disorders. This article reviews recent advances made in the understanding of this condition, potential pathophysiological mechanisms contributing to orthostatic intolerance, and therapeutic alternatives currently available for the management of these patients.

  10. Heat intolerance: predisposing factor or residual injury?

    Science.gov (United States)

    Epstein, Y

    1990-02-01

    Great individual variability exists in the ability to sustain heat stress. Some individuals are more susceptible to heat than others. Those individuals, among the young active population (athletes, military recruits, laborers), are at risk to contract exertional heat stroke. Low tolerance to heat results from either functional factors, or from congenital or acquired disturbances. In most cases heat intolerance can be foreseen. Cases of dehydration, overweight, low physical fitness, lack of acclimatization, febrile or infectious diseases, and skin disorders should be regarded a priori as predisposing factors for heat intolerance. Special attention should be paid to subjects with previous heat stroke episodes since it might reflect an underlying cause for heat susceptibility. The heat tolerance of these subjects should be tested 8-12 wk postepisode to detect a possible residual injury in the ability to thermoregulate adequately in the heat.

  11. Glucose and Fat Metabolism in Acromegaly: From Mice Models to Patient Care.

    Science.gov (United States)

    Dal, Jakob; List, Edward O; Jørgensen, Jens Otto L; Berryman, Darlene E

    2016-01-01

    Patients with active acromegaly are frequently insulin resistant, glucose intolerant, and at risk for developing overt type 2 diabetes. At the same time, these patients have a relatively lean phenotype associated with mobilization and oxidation of free fatty acids. These features are reversed by curative surgical removal of the growth hormone (GH)-producing adenoma. Mouse models of acromegaly share many of these characteristics, including a lean phenotype and proneness to type 2 diabetes. There are, however, also species differences with respect to oxidation rates of glucose and fat as well as the specific mechanisms underlying GH-induced insulin resistance. The impact of acromegaly treatment on insulin sensitivity and glucose tolerance depends on the treatment modality (e.g. somatostatin analogs also suppress insulin secretion, whereas the GH antagonist restores insulin sensitivity). The interplay between animal research and clinical studies has proven useful in the field of acromegaly and should be continued in order to understand the metabolic actions of GH. © 2015 S. Karger AG, Basel.

  12. Lactose intolerance: diagnosis, genetic, and clinical factors

    Science.gov (United States)

    Mattar, Rejane; de Campos Mazo, Daniel Ferraz; Carrilho, Flair José

    2012-01-01

    Most people are born with the ability to digest lactose, the major carbohydrate in milk and the main source of nutrition until weaning. Approximately 75% of the world’s population loses this ability at some point, while others can digest lactose into adulthood. This review discusses the lactase-persistence alleles that have arisen in different populations around the world, diagnosis of lactose intolerance, and its symptomatology and management. PMID:22826639

  13. Religious diversity, intolerance and civil conflict

    OpenAIRE

    Gomes, Joseph Flavian

    2013-01-01

    We compute new measures of religious diversity and intolerance and study their effects on civil conflict. Using a religion tree that describes the relationship between different religions, we compute measures of religious diversity at three different levels of aggregation. We find that religious diversity is a significant and robust correlate of civil conflict. While religious fractionalization significantly reduces conflict, religious polarization increases it. This is most robust at the sec...

  14. Antioxidant supplementation and obesity have independent effects on hepatic oxylipin profiles in insulin resistant, obese-prone rats

    Science.gov (United States)

    Objective - Elevated oxidative stress is associated with development of glucose intolerance. In this work, we tested the hypothesis that supplementation with the antioxidants vitamin E (d-alpha-tocopheryl acetate; 0.4 g/kg diet) and vitamin C (0.5 g/kg diet) prevents glucose intolerance in obese-pro...

  15. Intensive lifestyle intervention including high-intensity interval training program improves insulin resistance and fasting plasma glucose in obese patients

    Directory of Open Access Journals (Sweden)

    Guillaume Marquis-Gravel

    2015-01-01

    Conclusion: Following a 9-month intensive lifestyle intervention combining HIIT and MedD counseling, obese subjects experienced significant improvements of FPG and insulin resistance. This is the first study to expose the effects of a long-term program combining HIIT and MedD on glycemic control parameters among obese subjects.

  16. Obesity and the development of insulin resistance and impaired fasting glucose in black and white adolescent girls - A longitudinal study

    NARCIS (Netherlands)

    Klein, DJ; Friedman, LA; Harlan, WR; Barton, BA; Schreiber, GB; Cohen, RM; Harlan, LC; Morrison, JA

    Objective-Age at onset of type 2 diabetes has decreased during the past 20 years, especially in black women. Studies of factors associated with insulin resistance and hyperglycemia in preadolescent and adolescent populations are essential to understanding diabetes development. Research Design and

  17. Seafood Allergy, Toxicity, and Intolerance: A Review.

    Science.gov (United States)

    Prester, Ljerka

    2016-01-01

    Seafood allergies have been increasing their presence in the last 2 decades. Allergic reactions to seafood can range from mild urticarial and oral allergy syndrome to life-threatening anaphylactic reactions. Ingestion of seafood infested with Anisakis larvae can cause a disease known as anisakiasis with symptoms similar to true seafood allergy. Furthermore, some adverse reactions to seafood including histamine fish poisoning (HFP), and intolerance to histamine can trigger clinical symptoms, which, although nonallergic in origin, are similar to true immunoglobulin E (IgE)-mediated allergic reactions. Because seafood allergy usually remains a lifelong food allergy, this review focuses on the current knowledge on fish and shellfish allergens and emphasizes the importance of differentiating seafood allergy from other allergy-like reactions (anisakiasis, HFP, and intolerance to histamine). Key teaching points: • Fish and shellfish are potent allergens that can provoke serious IgE antibody-mediated adverse reactions in sensitive individuals. • Sensitization to seafood allergens can be achieved by ingestion, inhalation, or skin contact. • Shellfish major allergen, tropomyosin, shares significant homology to arthropods (dust mites and cockroaches). • Accidental exposures to seafood products cross-contaminated with fish or shellfish allergens (hidden allergens) during processing may present a health risk for sensitive individuals. • Allergens of fish parasite A. simplex present common hidden allergens in seafood, particularly in raw and undercooked home-made fish dishes. • Symptoms caused by HFP, histamine intolerance, and anisakiasis are similar to true seafood allergy.

  18. Lactase Non-persistence and Lactose Intolerance.

    Science.gov (United States)

    Bayless, Theodore M; Brown, Elizabeth; Paige, David M

    2017-05-01

    To evaluate the clinical and nutritional significance of genetically determined lactase non-persistence and potential lactose and milk intolerance in 65-70% of the world's adult population. Milk consumption is decreasing in the USA and is the lowest in countries with a high prevalence of lactase non-persistence. The dairy industry and Minnesota investigators have made efforts to minimize the influence of lactose intolerance on milk consumption. Some lactose intolerant individuals, without co-existent irritable bowel syndrome, are able to consume a glass of milk with a meal with no or minor symptoms. The high frequency of lactase persistence in offspring of Northern European countries and in some nomadic African tribes is due to mutations in the promoter of the lactase gene in association with survival advantage of milk drinking. Educational and commercial efforts to improve calcium and Vitamin D intake have focused on urging consumption of tolerable amounts of milk with a meal, use of lowered lactose-content foods including hard cheeses, yogurt, and lactose-hydrolyzed milk products.

  19. Religious Intolerance in the Cortes of Cadiz

    Directory of Open Access Journals (Sweden)

    Juan Pablo Domínguez

    2017-05-01

    Full Text Available In recent years there has been no shortage of studies on religious intolerance in the Cadiz Cortes, but many of them are burdened by two critical errors. The first one is to focus the arguments on article 12 of the Constitution, without paying attention to other parliamentary debates in which the intolerant policy of the Cortes was more clearly expounded. The second common mistake is to ignore the circumstances which prevented some deputies from freely speaking their minds on religious matters. Through a detailed analysis of the proceedings of the Cortes, as well as other sources of the period, this article is intended to remedy both shortcomings, and thus to question certain common assumptions in current historiography. This approach leads to the conclusion that, while some deputies may had hidden his penchant for freedom of conscience, the decrees and speeches of the Cortes were more intolerant than many suppose. Not only they ordered to punish all dissenters from the Church's doctrines, but they decreed death penalty for anyone who dared to suggest the introduction of religious freedom in Spain.

  20. Forkhead Box O6 (FoxO6) Depletion Attenuates Hepatic Gluconeogenesis and Protects against Fat-induced Glucose Disorder in Mice.

    Science.gov (United States)

    Calabuig-Navarro, Virtu; Yamauchi, Jun; Lee, Sojin; Zhang, Ting; Liu, Yun-Zi; Sadlek, Kelsey; Coudriet, Gina M; Piganelli, Jon D; Jiang, Chun-Lei; Miller, Rita; Lowe, Mark; Harashima, Hideyoshi; Dong, H Henry

    2015-06-19

    Excessive endogenous glucose production contributes to fasting hyperglycemia in diabetes. FoxO6 is a distinct member of the FoxO subfamily. To elucidate the role of FoxO6 in hepatic gluconeogenesis and assess its contribution to the pathogenesis of fasting hyperglycemia in diabetes, we generated FoxO6 knock-out (FoxO6-KO) mice followed by determining the effect of FoxO6 loss-of-function on hepatic gluconeogenesis under physiological and pathological conditions. FoxO6 depletion attenuated hepatic gluconeogenesis and lowered fasting glycemia in FoxO6-KO mice. FoxO6-deficient primary hepatocytes were associated with reduced capacities to produce glucose in response to glucagon. When fed a high fat diet, FoxO6-KO mice exhibited significantly enhanced glucose tolerance and reduced blood glucose levels accompanied by improved insulin sensitivity. These effects correlated with attenuated hepatic gluconeogenesis in FoxO6-KO mice. In contrast, wild-type littermates developed fat-induced glucose intolerance with a concomitant induction of fasting hyperinsulinemia and hyperglycemia. Furthermore, FoxO6-KO mice displayed significantly diminished macrophage infiltration into liver and adipose tissues, correlating with the reduction of macrophage expression of C-C chemokine receptor 2 (CCR2), a factor that is critical for regulating macrophage recruitment in peripheral tissues. Our data indicate that FoxO6 depletion protected against diet-induced glucose intolerance and insulin resistance by attenuating hepatic gluconeogenesis and curbing macrophage infiltration in liver and adipose tissues in mice. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Forkhead Box O6 (FoxO6) Depletion Attenuates Hepatic Gluconeogenesis and Protects against Fat-induced Glucose Disorder in Mice*

    Science.gov (United States)

    Calabuig-Navarro, Virtu; Yamauchi, Jun; Lee, Sojin; Zhang, Ting; Liu, Yun-Zi; Sadlek, Kelsey; Coudriet, Gina M.; Piganelli, Jon D.; Jiang, Chun-Lei; Miller, Rita; Lowe, Mark; Harashima, Hideyoshi; Dong, H. Henry

    2015-01-01

    Excessive endogenous glucose production contributes to fasting hyperglycemia in diabetes. FoxO6 is a distinct member of the FoxO subfamily. To elucidate the role of FoxO6 in hepatic gluconeogenesis and assess its contribution to the pathogenesis of fasting hyperglycemia in diabetes, we generated FoxO6 knock-out (FoxO6-KO) mice followed by determining the effect of FoxO6 loss-of-function on hepatic gluconeogenesis under physiological and pathological conditions. FoxO6 depletion attenuated hepatic gluconeogenesis and lowered fasting glycemia in FoxO6-KO mice. FoxO6-deficient primary hepatocytes were associated with reduced capacities to produce glucose in response to glucagon. When fed a high fat diet, FoxO6-KO mice exhibited significantly enhanced glucose tolerance and reduced blood glucose levels accompanied by improved insulin sensitivity. These effects correlated with attenuated hepatic gluconeogenesis in FoxO6-KO mice. In contrast, wild-type littermates developed fat-induced glucose intolerance with a concomitant induction of fasting hyperinsulinemia and hyperglycemia. Furthermore, FoxO6-KO mice displayed significantly diminished macrophage infiltration into liver and adipose tissues, correlating with the reduction of macrophage expression of C-C chemokine receptor 2 (CCR2), a factor that is critical for regulating macrophage recruitment in peripheral tissues. Our data indicate that FoxO6 depletion protected against diet-induced glucose intolerance and insulin resistance by attenuating hepatic gluconeogenesis and curbing macrophage infiltration in liver and adipose tissues in mice. PMID:25944898

  2. Involvement of KLF11 in hepatic glucose metabolism in mice via suppressing of PEPCK-C expression.

    Directory of Open Access Journals (Sweden)

    Huabing Zhang

    Full Text Available Abnormal hepatic gluconeogenesis is related to hyperglycemia in mammals with insulin resistance. Despite the strong evidences linking Krüppel-like factor 11 (KLF11 gene mutations to development of Type 2 diabetes, the precise physiological functions of KLF11 in vivo remain largely unknown.In current investigation, we showed that KLF11 is involved in modulating hepatic glucose metabolism in mice. Overexpression of KLF11 in primary mouse hepatocytes could inhibit the expression of gluconeogenic genes, including phosphoenolpyruvate carboxykinase (cytosolic isoform, PEPCK-C and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α, subsequently decreasing the cellular glucose output. Diabetic mice with overexpression of KLF11 gene in livers significantly ameliorated hyperglycemia and glucose intolerance; in contrast, the knockdown of KLF11 expression in db/m and C57BL/6J mice livers impaired glucose tolerance.Our data strongly indicated the involvement of KLF11 in hepatic glucose homeostasis via modulating the expression of PEPCK-C.

  3. Peripheral insulin resistance rather than beta cell dysfunction accounts for geographical differences in impaired fasting blood glucose among sub-Saharan African individuals: findings from the RODAM study.

    Science.gov (United States)

    Meeks, Karlijn A C; Stronks, Karien; Adeyemo, Adebowale; Addo, Juliet; Bahendeka, Silver; Beune, Erik; Owusu-Dabo, Ellis; Danquah, Ina; Galbete, Cecilia; Henneman, Peter; Klipstein-Grobusch, Kerstin; Mockenhaupt, Frank P; Osei, Kwame; Schulze, Matthias B; Spranger, Joachim; Smeeth, Liam; Agyem