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.

The biosynthesis of insulin and a probable precursor of insulin by a human islet cell adenoma.

Abstract: Because of the occurrence of two polypeptide chains in the insulin molecule, it has been proposed by several investigators, most recently by Givol et al.,I that it may be synthesized in vivo as a single large polypeptide chainwhich is converted byproteolysis to insulin after the native conformation has been established. This mechanism would undoubtedly ensure correct and efficient assembly in vivo. However, high yields of insulin have been obtained in vitro by recombination of separated or synthetic chains, especially when directing groups are employed.2 The results of Humbel3 also are consistent with a separate parallel synthesis of the two chains of angler fish insulin. Furthermore, Wang and Carpenter4 have looked for a \"proinsulin\" in pancreatic extracts but have concluded that if such exists, it comprises less than 10 per cent of the total insulin in the pancreas. The preponderant acinar tissue in the mammalian pancreas and its proteolytic enzymes has restricted most studies of insulin biosynthesis to a few species of teleost fish in which the islet tissue is separate from the pancreas.5' 6 Insulinproducing tumors of the islets of Langerhans, which occasionally occur in humans, are uniquely suited for the study of insulin biosynthesis since they are composed mainly of fB cells and are well separated from the surrounding acinar tissue. We recently obtained part of an islet cell adenoma that was removed from the pancreas of a patient with severe hypoglycemic episodes. When slices from this tumor were incubated with tritiated leucine or phenylalanine, the amiho acids were incorporated into insulin. A second labeled protein was separated from the acid-alcohol soluble fraction which could be shown to be related immunologically and chemically to insulin. Treatment of the second fraction with trypsin resulted in its conversion to a form that could not be distinguished from insulin. The results suggest that there is a precursor in the synthesis of insulin and that the precursor is a larger protein than insulin.

Early neonatal death in mice homozygous for a null allele of the insulin receptor gene

Abstract: Insulin action is viewed as a set of branching pathways, with some actions serving to regulate energy metabolism and others to regulate cellular growth and development1. Thus far, available genetic evidence has supported this view. In humans, complete lack of insulin receptors due to mutations of the insulin receptor gene results in severe growth retardation and mild diabetes2,3. In mice, targeted inactivation of insulin receptor sub-strate-1, an important substrate of the insulin receptor kinase, leads to inhibition of growth and mild resistance to the metabolic actions of insulin4,5. To address the question of whether both metabolic and growth-promoting actions of insulin are mediated by the insulin receptor, we have generated mice lacking insulin receptors by targeted mutagenesis in embryo-derived stem (ES) cells. Unlike human patients lacking insulin receptors6–9, mice homozygous for a null allele of the insulin receptor gene are born at term with apparently normal intrauterine growth and development. Within hours of birth, however, homozygous null mice develop severe hyperglycaemia and hyperketonaemia, and die as the result of diabetic ketoacidosis in 48–72 hours. These data are consistent with a model in which the insulin receptor functions primarily to mediate the metabolic actions of insulin.

Signaling by IL-6 promotes alternative activation of macrophages to limit endotoxemia and obesity-associated resistance to insulin

Abstract: Obesity and resistance to insulin are closely associated with the development of low-grade inflammation. Interleukin 6 (IL-6) is linked to obesity-associated inflammation; however, its role in this context remains controversial. Here we found that mice with an inactivated gene encoding the IL-6Rα chain of the receptor for IL-6 in myeloid cells (Il6ra(Δmyel) mice) developed exaggerated deterioration of glucose homeostasis during diet-induced obesity, due to enhanced resistance to insulin. Tissues targeted by insulin showed increased inflammation and a shift in macrophage polarization. IL-6 induced expression of the receptor for IL-4 and augmented the response to IL-4 in macrophages in a cell-autonomous manner. Il6ra(Δmyel) mice were resistant to IL-4-mediated alternative polarization of macrophages and exhibited enhanced susceptibility to lipopolysaccharide (LPS)-induced endotoxemia. Our results identify signaling via IL-6 as an important determinant of the alternative activation of macrophages and assign an unexpected homeostatic role to IL-6 in limiting inflammation.