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: Using cell-attached membrane patches from isolated rat pancreatic β-cells, this is the first report of a potassium channel whose activity is modulated by glucose, and which may couple metabolic and ionic events involved in the secretion of insulin.
Abstract: The major physiological stimulus for the secretion of insulin from the pancreatic beta-cell is an increase in the plasma glucose concentration. It is well established that glucose-stimulated insulin secretion is associated with the appearance of electrical activity in the beta-cell; glucose concentrations above the threshold level for insulin release produce a slow membrane depolarization followed by either oscillatory bursts of action potentials (5-15 mM glucose) or continuous spiking (greater than 16 mM glucose). Tracer flux studies and microelectrode measurements using intact islets of Langerhans have indicated that the initial depolarization induced by glucose is caused by a decrease in the resting membrane permeability to potassium. Evidence also suggests that the electrical, ionic and secretory responses to glucose are mediated by the metabolism of the sugar within the beta-cell. By using cell-attached membrane patches from isolated rat pancreatic beta-cells, we have now identified a potassium channel (G-channel) that is active at the resting potential and is inhibited by glucose. Closure of this channel requires glucose metabolism. This is the first report of a potassium channel whose activity is modulated by glucose, and which may couple metabolic and ionic events involved in the secretion of insulin.
1,111 citations
TL;DR: The results argue that the low malignant potential of tumors arising from TSC1-2 dysfunction may be explained by the failure of TSC mutant cells to activate PI3K and its downstream effectors.
Abstract: Insulin-like growth factors elicit many responses through activation of phosphoinositide 3-OH kinase (PI3K). The tuberous sclerosis complex (TSC1-2) suppresses cell growth by negatively regulating a protein kinase, p70S6K (S6K1), which generally requires PI3K signals for its activation. Here, we show that TSC1-2 is required for insulin signaling to PI3K. TSC1-2 maintains insulin signaling to PI3K by restraining the activity of S6K, which when activated inactivates insulin receptor substrate (IRS) function, via repression of IRS-1 gene expression and via direct phosphorylation of IRS-1. Our results argue that the low malignant potential of tumors arising from TSC1-2 dysfunction may be explained by the failure of TSC mutant cells to activate PI3K and its downstream effectors.
1,109 citations
TL;DR: Exercise 24 hours before the euglycemic clamp increased phosphorylation of insulin receptor and IRS-1 in obese and diabetic subjects but did not increase glucose uptake or PI 3-kinase association with IRS- 1 upon insulin stimulation, which defines a key step in insulin resistance.
Abstract: The broad nature of insulin resistant glucose metabolism in skeletal muscle of patients with type 2 diabetes suggests a defect in the proximal part of the insulin signaling network. We sought to identify the pathways compromised in insulin resistance and to test the effect of moderate exercise on whole-body and cellular insulin action. We conducted euglycemic clamps and muscle biopsies on type 2 diabetic patients, obese nondiabetics and lean controls, with and without a single bout of exercise. Insulin stimulation of the phosphatidylinositol 3-kinase (PI 3-kinase) pathway, as measured by phosphorylation of the insulin receptor and IRS-1 and by IRS protein association with p85 and with PI 3-kinase, was dramatically reduced in obese nondiabetics and virtually absent in type 2 diabetic patients. Insulin stimulation of the MAP kinase pathway was normal in obese and diabetic subjects. Insulin stimulation of glucose-disposal correlated with association of p85 with IRS-1. Exercise 24 hours before the euglycemic clamp increased phosphorylation of insulin receptor and IRS-1 in obese and diabetic subjects but did not increase glucose uptake or PI 3-kinase association with IRS-1 upon insulin stimulation. Thus, insulin resistance differentially affects the PI 3-kinase and MAP kinase signaling pathways, and insulin-stimulated IRS-1-association with PI 3-kinase defines a key step in insulin resistance.
1,106 citations
TL;DR: A change of the proportions of dietary fatty acids, decreasing saturated fatty acid and increasing monounsaturated fatty acid, improves insulin sensitivity but has no effect on insulin secretion.
Abstract: Aims/hypothesis. The amount and quality of fat in the diet could be of importance for development of insulin resistance and related metabolic disorders. Our aim was to determine whether a change in dietary fat quality alone could alter insulin action in humans. Methods. The KANWU study included 162 healthy subjects chosen at random to receive a controlled, isoenergetic diet for 3 months containing either a high proportion of saturated (SAFA diet) or monounsaturated (MUFA diet) fatty acids. Within each group there was a second assignment at random to supplements with fish oil (3.6 g n-3 fatty acids/d) or placebo. Results. Insulin sensitivity was significantly impaired on the saturated fatty acid diet (-10 %, p = 0.03) but did not change on the monounsaturated fatty acid diet ( + 2 %, NS) (p = 0.05 for difference between diets). Insulin secretion was not affected. The addition of n-3 fatty acids influenced neither insulin sensitivity nor insulin secretion. The favourable effects of substituting a monounsaturated fatty acid diet for a saturated fatty acid diet on insulin sensitivity were only seen at a total fat intake below median (37E %). Here, insulin sensitivity was 12.5 % lower and 8.8 % higher on the saturated fatty acid diet and monounsaturated fatty acid diet respectively (p = 0.03). Low density lipoprotein cholesterol (LDL) increased on the saturated fatty acid diet ( + 4.1 %, p 37E %). [Diabetologia (2001) 44: 312–319]
1,101 citations
TL;DR: Results suggest that, as for leptin, circulating IL-6 concentrations reflect, at least in part, adipose tissue production reduced after weight loss, and could play a role in the improved sensitivity to insulin observed in these patients.
Abstract: The aim of this study was to investigate the potential role of adipose cytokines in the obesity-associated insulin resistance. To that end, we compared: 1) serum concentrations of interleukin 6 (IL-6), tumor necrosis factor a (TNFa), and leptin in eight healthy lean control females and in android obese female without (n 5 14) and with (n 5 7) type 2 diabetes; and 2) the levels of these cytokines both in serum and in sc adipose tissue in the 14 obese nondiabetic women before and after 3 weeks of a very low-calorie diet (VLCD). As compared with lean controls, obese nondiabetic and diabetic patients were more insulin resistant and presented increased values for leptin, IL-6, TNFa, and C-reactive protein. In the whole group, IL-6 values were more closely related to the parameters evaluating insulin resistance than leptin or TNFa values. VLCD resulted in weight loss and decreased body fat mass (;3 kg). Insulin sensitivity was improved with no significant change in both serum and adipose tissue TNFa levels. In contrast, VLCD induced significant decreases in IL-6 and leptin levels in both adipose tissue and serum. These results suggest that, as for leptin, circulating IL-6 concentrations reflect, at least in part, adipose tissue production. The reduced production and serum concentrations after weight loss could play a role in the improved sensitivity to insulin observed in these patients. (J Clin Endocrinol Metab 85: 3338 ‐3342, 2000)
1,099 citations