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.

Quantitative aspects of the reaction between insulin and insulin-binding antibody.

Abstract: The presence of insulin-binding antibodies in the serums of insulin-treated subjects has been reported previously (1). With I\"ll-labeled insulin it has been shown that the antigen-antibody complexes do not precipitate, that the binding of insulin to antibody is a reversible process, and that, at constant antibody concentration, the ratio of bound insulin to free insulin is an inverse function of the concentration of insulin (1). In the present studies, experimental data on the reaction between insulin and insulin-binding antibody are tested against several theoretical models. The results are most compatible with a model composed of a univalent insulin reacting with two distinctly different orders of antibody sites. Data for equilibrium constants, forward and reverse velocity constants and various ther-modynamic constants are presented in terms of the model chosen. METHODS Antiserums were obtained from insulin-treated diabetic and schizophrenic subjects generally at least 24 hours and frequently many weeks following the last injection of insulin and were stored frozen or at 40 C. for weeks or months prior to use. Insulin-I131 was prepared from crystalline beef insulin' with specific activities of 10 to 100 mc. per mg. Methods employed in preparation and in protection of the insulin against extensive radiation damage have been described (2, 3). However, because of the extremely high specific activities of the preparations and the trauma incident to the labeling procedure, storage and dilution, occasionally as much as 10 per cent of the insulin-I'3l was damaged by the time of use. Recent preparations, with which the bulk of the quantitative data has been obtained, have uniformly contained less than 5 per cent damaged components. All dilutions were made in water or veronal buffer,2 0.1 ionic strength, pH 8.6, to which was added 2 per cent ' We are indebted to Dr. 0. K. Behrens and Dr. C. W. Pettinga of the Eli Lilly laboratories for generous supplies of crystalline beef insulin. 2 No significant differences in binding were detected when duplicate specimens of the same antiserum were diluted in water and in veronal. serum albumin to minimize losses of insulin or antibody by adsorption on glassware. Two types of experiments were performed. In one, henceforth termed \"equilibrium state\" studies, various relative concentrations of antiserum and insulin, including tracer quantities of insulin-I'3l, were incubated together at 370 C. The mixtures were allowed to come to equilibrium and were then analyzed for their content of free and bound insulin. No …

TNF-α Is a Predictor of Insulin Resistance in Human Pregnancy

Abstract: Historically, insulin resistance during pregnancy has been ascribed to increased production of placental hormones and cortisol. The purpose of this study was to test this hypothesis by correlating the longitudinal changes in insulin sensitivity during pregnancy with changes in placental hormones, cortisol, leptin, and tumor necrosis factor (TNF)-alpha. Insulin resistance was assessed in 15 women (5 with gestational diabetes mellitus [GDM] and 10 with normal glucose tolerance) using the euglycemic-hyperinsulinemic clamp procedure, before pregnancy (pregravid) and during early (12-14 weeks) and late (34-36 weeks) gestation. Body composition, plasma TNF-alpha, leptin, cortisol, and reproductive hormones (human chorionic gonadotropin, estradiol, progesterone, human placental lactogen, and prolactin) were measured in conjunction with the clamps. Placental TNF-alpha was measured in vitro using dually perfused human placental cotyledon from five additional subjects. Compared with pregravid, insulin resistance was evident during late pregnancy in all women (12.4 +/- 1.2 vs. 8.1 +/- 0.8 10(-2) mg. kg(-1) fat-free mass. min(-1). microU(-1). ml(-1)). TNF-alpha, leptin, cortisol, all reproductive hormones, and fat mass were increased in late pregnancy (P < 0.001). In vitro, most of the placental TNF-alpha (94%) was released into the maternal circulation; 6% was released to the fetal side. During late pregnancy, TNF-alpha was inversely correlated with insulin sensitivity (r = -0.69, P < 0.006). Furthermore, among all of the hormonal changes measured in this study, the change in TNF-alpha from pregravid to late pregnancy was the only significant predictor of the change in insulin sensitivity (r = -0.60, P < 0.02). The placental reproductive hormones and cortisol did not correlate with insulin sensitivity in late pregnancy. Multivariate stepwise regression analysis revealed that TNF-alpha was the most significant independent predictor of insulin sensitivity (r = -0.67, P < 0.0001), even after adjustment for fat mass by covariance (r = 0.46, P < 0.01). These observations challenge the view that the classical reproductive hormones are the primary mediators of change in insulin sensitivity during gestation and provide the basis for including TNF-alpha in a new paradigm to explain insulin resistance in pregnancy.

Hemodynamic actions of insulin

Abstract: There is accumulating evidence that insulin has a physiological role to vasodilate skeletal muscle vasculature in humans. This effect occurs in a dose-dependent fashion within a half-maximal respon...

Perspectives in Diabetes Diabetes and Cardiovascular Disease The "Common Soil" Hypothesis

Abstract: with an enhanced risk of both diabetes and cardiovascular disease many decades later. These same adverse environmental conditions are also associated with the development in adult life of abdominal obesity and the insulin-resistance syndrome (IRS). The IRS consists of glucose intolerance, hyperinsulinemia, dyslipidemia (high triglyceride and low high-density lipoprotein [HDL] cholesterol levels), and hypertension. Although the mechanism underlying this cluster is controversial, the statistical association is well established. All of the elements of the IRS have been documented as risk factors for type I1 diabetes. Some, but not all, of these elements are also cardiovascular disease risk factors, in particular, hypertension and low HDL cholesterol. Other factors associated with the IRS that may enhance cardiovascular disease risk are plasminogen activator inhibitor 1 and small, dense low-density lipoprotein particles. Whether insulin itself is a risk factor remains controversial, but recent epidemiological evidence has been mostly negative. This question has marked clinical relevance because if the IRS enhances cardiovascular disease risk by virtue of its concomitant factors and not the hyperinsulinemia per ee, this would tend to alleviate concerns that intensive insulin management of type I1 diabetic subjects could enhance the risk of large-vessel atherosclerosis. Clinical trials are urgently needed to settle this point. Diabetes 44:369-374, 1995