Molecular mechanisms of insulin resistance in diabetes

Abstract

Molecular components of impaired insulin signaling pathway have emerged with growing interest to under stand how the environment and genetic susceptibility combine to cause defects in this fundamental pathway that lead to insulin resistance. When insulin resistance is combined with β-cell defects in glucose-stimulated insulin secretion, impaired glucose tolerance, hyperglycemia, or Type 2 diabetes can result. The most common underlying cause is obesity, although primary insulin resistance in normal-weight individuals is also possible. The adipose tissue releases free fatty acids that contribute to insulin resistance and also acts as a relevant endocrine organ producing mediators (adipokines) that can modulate insulin signalling. This chapter deals with the core elements promoting insulin resistance, associated with impaired insulin signalling pathway and adipocyte dysfunction. A detailed understanding of these basic pathophysiological mechanisms is critical for the development of novel therapeutic strategies to treat diabetes.