Insulin resistance: a phosphorylation-based uncoupling of insulin signaling.

ABSTRACT

Insulin resistance refers to a decreased capacity of circulating insulin to regulate nutrient metabolism. It is associated with the development of type 2 diabetes--an ever-increasing epidemic of the 21st century. Recent studies reveal that agents that induce insulin resistance exploit phosphorylation-based negative-feedback control mechanisms, otherwise utilized by insulin itself, to uncouple the insulin receptor from its downstream effectors and thereby terminate insulin signal transduction. This article describes recent findings that present novel viewpoints of the molecular basis of insulin resistance, focusing on the cardinal role of Ser/Thr protein kinases as emerging key players in this arena.