Insulin resistance in type 2 diabetes mellitus

Abstract

Insulin resistance is an integral pathophysiological feature of type 2 diabetes mellitus. Here, we review established and emerging cellular mechanisms of insulin resistance, their complex integrative features and their relevance to disease progression. While recognizing the heterogeneity of the elusive fundamental disruptions that cause insulin resistance, we endorse the view that effector mechanisms impinge on insulin receptor signalling and its relationship with plasma levels of insulin. We focus on hyperinsulinaemia and its consequences: acutely impaired but persistent insulin action, with reduced ability to lower glucose levels but preserved lipid synthesis and lipoprotein secretion. We emphasize the role of insulin sensitization as a therapeutic goal in type 2 diabetes mellitus. This Review covers the mechanistic relationship between hyperinsulinaemia and insulin resistance in type 2 diabetes mellitus. The article discusses how changes in insulin signalling affect metabolism and disease progression in various organs and cell types.