Molecular Mechanisms of Insulin Resistance in Type 2 Diabetes Mellitus

Overview

Journal World J Diabetes

Publisher Baishideng Publishing Group

Specialty Endocrinology

Date 2011 May 4

PMID 21537430

Citations 78

Authors

Vandana Saini

Affiliations

Soon will be listed here.

Abstract

Free fatty acids are known to play a key role in promoting loss of insulin sensitivity in type 2 diabetes mellitus but the underlying mechanism is still unclear. It has been postulated that an increase in the intracellular concentration of fatty acid metabolites activates a serine kinase cascade, which leads to defects in insulin signaling downstream to the insulin receptor. In addition, the complex network of adipokines released from adipose tissue modulates the response of tissues to insulin. Among the many molecules involved in the intracellular processing of the signal provided by insulin, the insulin receptor substrate-2, the protein kinase B and the forkhead transcription factor Foxo 1a are of particular interest, as recent data has provided strong evidence that dysfunction of these proteins results in insulin resistance in vivo. Recently, studies have revealed that phosphoinositidedependent kinase 1-independent phosphorylation of protein kinase Cε causes a reduction in insulin receptor gene expression. Additionally, it has been suggested that mitochondrial dysfunction triggers activation of several serine kinases, and weakens insulin signal transduction. Thus, in this review, the current developments in understanding the pathophysiological processes of insulin resistance in type 2 diabetes have been summarized. In addition, this study provides potential new targets for the treatment and prevention of type 2 diabetes.

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