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.

Relationship of plasma insulin levels to the incidence of myocardial infarction and coronary heart disease mortality in a middle-aged population.

Abstract: The possible role of plasma insulin levels as a risk factor of coronary heart disease has been studied in a population of 7246 non diabetic, working men, aged 43–54 years, initially free from heart disease, and followed for 63 months on average. 128 new coronary heart disease events (non fatal myocardial infarction and coronary related deaths) were detected during this period. The annual risk is analysed by a multivariate model including age, serum cholesterol and triglycerides, blood pressure, smoking, obesity, plasma glucose and insulin fasting and 2 hours after a 75 g oral glucose load. It is shown that the fasting plasma insulin level and the fasting insulin-glucose ratio are positively associated with risk independent of the other factors. The same variables, 2 hours after the glucose load are also positively associated with risk but their contributions are not significant in the multivariate analysis. It is concluded that high insulin levels may constitute an independent risk factor for coronary heart disease complications in middle aged non diabetic men.

A new rat model of type 2 diabetes: the fat-fed, streptozotocin-treated rat.

Abstract: This study was initiated to develop an animal model of type 2 diabetes in a non-obese, outbred rat strain that replicates the natural history and metabolic characteristics of the human syndrome and is suitable for pharmaceutical research. Male Sprague-Dawley rats (n = 31), 7 weeks old, were fed normal chow (12% of calories as fat), or high-fat diet (40% of calories as fat) for 2 weeks and then injected with streptozotocin (STZ, 50 mg/kg intravenously). Before STZ injection, fat-fed rats had similar glucose concentrations to chow-fed rats, but significantly higher insulin, free fatty acid (FFA), and triglyceride (TG) concentrations (P < .01 to .0001). Plasma insulin concentrations in response to oral glucose (2 g/kg) were increased 2-fold by fat feeding (P < .01), and adipocyte glucose clearance under maximal insulin stimulation was significantly reduced (P < .001), suggesting that fat feeding induced insulin resistance. STZ injection increased glucose (P < .05), insulin (P < .05), FFA (P < .05), and TG (P < .0001) concentrations in fat-fed rats (Fat-fed/STZ rats) compared with chow-fed, STZ-injected rats (Chow-fed/STZ rats). Fat-fed/STZ rats were not insulin deficient compared with normal chow-fed rats, but had hyperglycemia and a somewhat higher insulin response to an oral glucose challenge (both P < .05). In addition, insulin-stimulated adipocyte glucose clearance was reduced in Fat-fed/STZ rats compared with both chow-fed and Chow-fed/STZ rats (P < .001). Finally, Fat-fed/STZ rats were sensitive to the glucose lowering effects of metformin and troglitazone. In conclusion, Fat-fed/STZ rats provide a novel animal model for type 2 diabetes, simulates the human syndrome, and is suitable for the testing of antidiabetic compounds.

Acute stimulation of glucose metabolism in mice by leptin treatment.

Abstract: Leptin is an adipocyte hormone that functions as an afferent signal in a negative feedback loop regulating body weight, and acts by interacting with a receptor in the hypothalamus and other tissues. Leptin treatment has potent effects on lipid metabolism, and leads to a large, specific reduction of adipose tissue mass after several days. Here we show that leptin also acts acutely to increase glucose metabolism, although studies of leptin's effect on glucose metabolism have typically been confounded by the weight-reducing actions of leptin treatment, which by itself could affect glucose homoeostasis. We have demonstrated acute in vivo effects of intravenous and intracerebroventricular administrations of leptin on glucose metabolism. A five-hour intravenous infusion of leptin into wild-type mice increased glucose turnover and glucose uptake, but decreased hepatic glycogen content. The plasma levels of insulin and glucose did not change. Similar effects were observed after both intravenous and intracerebroventricular infusion of leptin, suggesting that effects of leptin on glucose metabolism are mediated by the central nervous system (CNS). These data indicate that leptin induces a complex metabolic response with effects on glucose as well as lipid metabolism. This response is unique to leptin, which suggests that new efferent signals emanate from the CNS after leptin treatment.

The Role of Incretins in Glucose Homeostasis and Diabetes Treatment

Abstract: Incretins are gut hormones that are secreted from enteroendocrine cells into the blood within minutes after eating. One of their many physiological roles is to regulate the amount of insulin that is secreted after eating. In this manner, as well as others to be described in this review, their final common raison d'etre is to aid in disposal of the products of digestion. There are two incretins, known as glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1), that share many common actions in the pancreas but have distinct actions outside of the pancreas. Both incretins are rapidly deactivated by an enzyme called dipeptidyl peptidase 4 (DPP4). A lack of secretion of incretins or an increase in their clearance are not pathogenic factors in diabetes. However, in type 2 diabetes (T2DM), GIP no longer modulates glucose-dependent insulin secretion, even at supraphysiological (pharmacological) plasma levels, and therefore GIP incompetence is detrimental to beta-cell function, especially after eating. GLP-1, on the other hand, is still insulinotropic in T2DM, and this has led to the development of compounds that activate the GLP-1 receptor with a view to improving insulin secretion. Since 2005, two new classes of drugs based on incretin action have been approved for lowering blood glucose levels in T2DM: an incretin mimetic (exenatide, which is a potent long-acting agonist of the GLP-1 receptor) and an incretin enhancer (sitagliptin, which is a DPP4 inhibitor). Exenatide is injected subcutaneously twice daily and its use leads to lower blood glucose and higher insulin levels, especially in the fed state. There is glucose-dependency to its insulin secretory capacity, making it unlikely to cause low blood sugars (hypoglycemia). DPP4 inhibitors are orally active and they increase endogenous blood levels of active incretins, thus leading to prolonged incretin action. The elevated levels of GLP-1 are thought to be the mechanism underlying their blood glucose-lowering effects.

Chromium in Human Nutrition: A Review

Abstract: This review summarizes the results of 15 controlled studies supplementing defined Cr(III) compounds to subjects with impaired glucose tolerance. Three of these (3-4 mumol Cr/d for > 2 mo) produced no beneficial effects: serum glucose, insulin and lipid concentrations remained unchanged. The remaining 12 interventions improved the efficiency of insulin or the blood lipid profile of subjects (ranging from malnourished children and healthy middle-aged individuals to insulin-requiring diabetics). In addition, three cases of impaired glucose tolerance after long-term total parenteral alimentation responding to Cr supplementation have been reported. Chromium potentiates the action of insulin in vitro and in vivo; maximal in vitro activity requires a special chemical form, termed Glucose Tolerance Factor and tentatively identified as a Cr-nicotinic acid complex. Its complete structural identification is a major challenge to chromium research. The development and validation of a procedure to diagnose chromium status is the second challenge. Such a test would allow the assessment of incidence and severity of deficiency in the population and the selection of deficiency in the population and the selection of chromium-responsive individuals. The third challenge is the definition of chromium's mode of action on parameters of lipid metabolism that have been reported from some studies but not others. Future research along these lines might establish whether chromium deficiency is a factor in the much discussed "Syndrome X" of insulin resistance.