Topic
Insulin
About: Insulin is a research topic. Over the lifetime, 124295 publications have been published within this topic receiving 5129734 citations. The topic is also known as: human insulin.
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TL;DR: In summary, insulin does not stimulate leptin production acutely; however, a long-term effect of insulin on leptin production could be demonstrated both in vivo and in vitro, suggesting that insulin regulates OB gene expression and leptin production indirectly, probably through its trophic effect on adipocytes.
Abstract: This study was undertaken to investigate the changes in obesity (OB) gene expression and production of leptin in response to insulin in vitro and in vivo under euglycemic and hyperglycemic conditions in humans. Three protocols were used: 1) euglycemic clamp with insulin infusion rates at 40, 120, 300, and 1,200 mU / m / min carried out for up to 5 h performed in 16 normal lean individuals, 30 obese individuals, and 31 patients with NIDDM; 2) 64-to 72-h hyperglycemic (glucose 12.6 mmol/l) clamp performed on 5 lean individuals; 3) long-term (96-h) primary culture of isolated abdominal adipocytes in the presence and absence of 100 nmol/l insulin. Short-term hyperinsulinemia in the range of 80 to > 10,000 microU/ml had no effect on circulating levels of leptin. During the prolonged hyperglycemic clamp, a rise in leptin was observed during the last 24 h of the study (P < 0.001). In the presence of insulin in vitro, OB gene expression increased at 72 h (P < 0.01), followed by an increase in leptin released to the medium (P < 0.001). In summary, insulin does not stimulate leptin production acutely; however, a long-term effect of insulin on leptin production could be demonstrated both in vivo and in vitro. These data suggest that insulin regulates OB gene expression and leptin production indirectly, probably through its trophic effect on adipocytes.
734 citations
TL;DR: Although enlarged mean subcutaneous abdominal adipocyte size is associated with insulin resistance cross-sectionally, prospectively, both abnormalities are independent and additive predictors of Type II diabetes.
Abstract: Aims/hypothesis. Cross-sectional studies indicate that enlarged subcutaneous abdominal adipocyte size is associated with hyperinsulinaemia, insulin resistance and glucose intolerance. To further explore the pathophysiological significance of these associations, we examined prospectively whether enlarged subcutaneous abdominal adipocyte size predicts Type II (non-insulin-dependent) diabetes mellitus. Methods. Body composition (hydrodensitometry), mean subcutaneous abdominal adipocyte size (fat biopsy), insulin sensitivity (hyperinsulinaemic clamp) and the acute insulin secretory response (25-g i. v. GTT) were assessed in 280 Pima Indians with either normal (NGT), impaired (IGT) or diabetic glucose tolerance (75-g OGTT). Subjects with NGT were then followed prospectively. Results. After adjusting for age, sex and per cent body fat, mean subcutaneous abdominal adipocyte size was 19 % and 11 % higher in subjects with diabetes and IGT, compared with those with NGT (p < 0.001). Insulin sensitivity was inversely correlated with mean subcutaneous abdominal adipocyte size (r = –0.53, p < 0.0001), even after adjusting for per cent body fat (r = –0.31, p < 0.001). In 108 NGT subjects followed over 9.3 ± 4.1 years (33 of whom developed diabetes), enlarged mean subcutaneous abdominal adipocyte size but not high per cent body fat, was an independent predictor of diabetes, in addition to a low insulin sensitivity and acute insulin secretory response [relative hazard 10th vs 90th centile (95 % CI): 5.8 (1.7–19.6), p < 0.005]. In 28 NGT subjects with a 9 % weight gain over 2.7 ± 1.3 years, changes in insulin sensitivity were inversely and independently related to changes in mean subcutaneous abdominal adipocyte size and per cent body fat. Conclusion/interpretation. Although enlarged mean subcutaneous abdominal adipocyte size is associated with insulin resistance cross-sectionally, prospectively, both abnormalities are independent and additive predictors of Type II diabetes. [Diabetologia (2000) 43: 1498–1506]
734 citations
TL;DR: It is demonstrated that a specific subset of ARBs induces PPARγ activity, thereby promoting PPARαγ-dependent differentiation in adipocytes, providing a potential mechanism for their insulin-sensitizing/antidiabetic effects.
Abstract: Background— Angiotensin type 1 receptor (AT1R) blockers (ARB) have been shown to reduce the incidence of type 2 diabetes mellitus by an unknown molecular mechanism. The peroxisome proliferator–activated receptor-γ (PPARγ) is the central regulator of insulin and glucose metabolism improving insulin sensitivity. We investigated the regulation of PPARγ function by ARBs. Methods and Results— The ARBs irbesartan and telmisartan (10 μmol/L) potently enhanced PPARγ-dependent 3T3-L1 adipocyte differentiation associated with a significant increase in mRNA expression of the adipogenic marker gene adipose protein 2 (aP2), as measured by quantitative real-time polymerase chain reaction (irbesartan: 3.3±0.1-fold induction; telmisartan: 3.1±0.3-fold induction; both P<0.01). Telmisartan showed a more pronounced induction of aP2 expression in lower, pharmacologically relevant concentrations compared with the other ARBs. The ARB losartan enhanced aP2 expression only at high concentrations (losartan 100 μmol/L: 3.6±0.3-fol...
734 citations
TL;DR: Interleukin-6 mediates crosstalk between insulin-sensitive tissues, intestinal L cells and pancreatic islets to adapt to changes in insulin demand and suggests that drugs modulating this loop may be useful in type 2 diabetes.
Abstract: Exercise, obesity and type 2 diabetes are associated with elevated plasma concentrations of interleukin-6 (IL-6). Glucagon-like peptide-1 (GLP-1) is a hormone that induces insulin secretion. Here we show that administration of IL-6 or elevated IL-6 concentrations in response to exercise stimulate GLP-1 secretion from intestinal L cells and pancreatic alpha cells, improving insulin secretion and glycemia. IL-6 increased GLP-1 production from alpha cells through increased proglucagon (which is encoded by GCG) and prohormone convertase 1/3 expression. In models of type 2 diabetes, the beneficial effects of IL-6 were maintained, and IL-6 neutralization resulted in further elevation of glycemia and reduced pancreatic GLP-1. Hence, IL-6 mediates crosstalk between insulin-sensitive tissues, intestinal L cells and pancreatic islets to adapt to changes in insulin demand. This previously unidentified endocrine loop implicates IL-6 in the regulation of insulin secretion and suggests that drugs modulating this loop may be useful in type 2 diabetes.
731 citations
TL;DR: In vitro studies raise the possibility that leptin modulates insulin activities in obese individuals by causing attenuation of several insulin-induced activities and increasing the activity of IRS-1-associated phosphatidylinositol 3-kinase.
Abstract: Leptin mediates its effects on food intake through the hypothalamic form of its receptor OB-R. Variants of OB-R are found in other tissues, but their function is unknown. Here, an OB-R variant was found in human hepatic cells. Exposure of these cells to leptin, at concentrations comparable with those present in obese individuals, caused attenuation of several insulin-induced activities, including tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1), association of the adapter molecule growth factor receptor-bound protein 2 with IRS-1, and down-regulation of gluconeogenesis. In contrast, leptin increased the activity of IRS-1-associated phosphatidylinositol 3-kinase. These in vitro studies raise the possibility that leptin modulates insulin activities in obese individuals.
730 citations