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.

Type 2 Diabetes-a Matter of ß-Cell Life and Death?

Abstract: In type 2 diabetes, the β cells of the pancreas fail to produce enough insulin to meet the body's demand, in part because of an acquired decrease in β-cell mass. In adults, pancreatic β-cell mass is controlled by several mechanisms, including β-cell replication, neogenesis, hypertrophy, and survival. Here, I discuss evidence supporting the notion that increased β-cell apoptosis is an important factor contributing to β-cell loss and the onset of type 2 diabetes. Interestingly, a key signaling molecule that promotes β-cell growth and survival, insulin receptor substrate 2 (IRS-2), is a member of a family of proteins whose inhibition contributes to the development of insulin resistance in the liver and other insulin-responsive tissues. Thus, the IRS-2 pathway appears to be a crucial participant in the tenuous balance between effective pancreatic β-cell mass and insulin resistance.

TRB3: A tribbles Homolog That Inhibits Akt/PKB Activation by Insulin in Liver

Abstract: Insulin resistance is a major hallmark in the development of type II diabetes, which is characterized by the failure of insulin to promote glucose uptake in muscle and to suppress glucose production in liver. The serine-threonine kinase Akt (PKB) is a principal target of insulin signaling that inhibits hepatic glucose output when glucose is available from food. Here we show that TRB3, a mammalian homolog of Drosophila tribbles, functions as a negative modulator of Akt. TRB3 expression is induced in liver under fasting conditions, and TRB3 disrupts insulin signaling by binding directly to Akt and blocking activation of the kinase. Amounts of TRB3 RNA and protein were increased in livers of db/db diabetic mice compared with those in wild-type mice. Hepatic overexpression of TRB3 in amounts comparable to those in db/db mice promoted hyperglycemia and glucose intolerance. Our results suggest that, by interfering with Akt activation, TRB3 contributes to insulin resistance in individuals with susceptibility to type II diabetes.

The Relation between Insulin Sensitivity and the Fatty-Acid Composition of Skeletal-Muscle Phospholipids

Abstract: Background Insulin resistance and hyperinsulinemia are features of obesity, non-insulin-dependent diabetes mellitus, and other disorders. Skeletal muscle is a major site of insulin action, and insulin sensitivity may be related to the fatty-acid composition of the phospholipids within the muscle membranes involved in the action of insulin. Methods We determined the relation between the fatty-acid composition of skeletal-muscle phospholipids and insulin sensitivity in two groups of subjects. In one study, we obtained samples of the rectus abdominis muscle from 27 patients undergoing coronary artery surgery; fasting serum insulin levels provided an index of insulin sensitivity. In the second study, a biopsy of the vastus lateralis muscle was performed in 13 normal men, and insulin sensitivity was assessed by euglycemic-clamp studies. Results In the patients undergoing surgery, the fasting serum insulin concentration (a measure of insulin resistance) was negatively correlated with the percentage of individua...

Fasting Insulin and Outcome in Early-Stage Breast Cancer: Results of a Prospective Cohort Study

Abstract: PURPOSE: Insulin, a member of a family of growth factors that includes insulin-like growth factor (IGF)-I and IGF-II, exerts mitogenic effects on normal and malignant breast epithelial cells, acting via insulin and IGF-I receptors. Because of this and because of its recognized association with obesity, an adverse prognostic factor in breast cancer, we examined the prognostic associations of insulin in early-stage breast cancer. PATIENTS AND METHODS: A cohort of 512 women without known diabetes, who had early-stage (T1 to T3, N0 to N1, and M0) breast cancer, was assembled and observed prospectively. Information on traditional prognostic factors and body size was collected, and fasting blood was obtained. RESULTS: Fasting insulin was associated with distant recurrence and death; the hazard ratios and 95% confidence intervals (CI) for those in the highest (> 51.9 pmol/L) versus the lowest (< 27.0 pmol/L) insulin quartile were 2.0 (95% CI, 1.2 to 3.3) and 3.1 (95% CI, 1.7 to 5.7), respectively. There was some...

Insulin in the brain: a hormonal regulator of energy balance.

Abstract: I. Introduction EARLY studies of brain glucose metabolism established the axiom that insulin is not required for utilization of glucose by the central nervous system (CNS) (1). A corollary to this concept was the belief that circulating insulin is incapable of crossing the bloodbrain barrier (BBB) and is therefore without effects in the brain. While the first of these tenets remains unchallenged, the second has been subjected to detailed scrutiny for over a decade, following the identification of both insulin (2) and its receptor (3) in the adult mammalian brain. Early reports of relatively high concentrations of insulin in brain extracts raised the possibility that insulin is synthesized and released locally in the CNS, as had been established for several other peptide hormones (2). Recent investigations, however, indicate that “brain insulin” is derived largely from the circulation (4), and a growing body of evidence suggests that its delivery into the neuropil may be facilitated by a specialized BBB tr...