Insulin resistance in skeletal muscle and adipose tissue in polycystic ovary syndrome: are the molecular mechanisms distinct from type 2 diabetes?

Abstract

The association of polycystic ovary syndrome (PCOS) with insulin resistance was recognized almost three decades ago. Despite the pivotal role of insulin resistance in the pathogenesis of PCOS, the precise cellular and molecular mechanisms of impaired insulin action remain elusive. This review has two aims: 1) to review the mechanisms of insulin resistance, specifically impaired insulin-stimulated glucose transport, in skeletal muscle and adipose tissue in PCOS, and 2) to assess whether mechanisms of insulin resistance in PCOS are distinct from those in type 2 diabetes. As in type 2 diabetes, studies in skeletal muscle in PCOS support the existence of intrinsic defects in insulin signalling but also underscore the importance of in vivo environmental factors for the development of insulin resistance. In PCOS and type 2 diabetes, similar insulin signalling defects in muscle have been described i.e. impaired signalling via IRS-1 and up-regulation of ERK signalling. Similar defects in insulin signalling have also been described in adipose tissue in PCOS and type 2 diabetes, but data are limited. As for type 2 diabetes, PCOS is characterized by chronic inflammation, mitochondrial dysfunction and cellular stress. Androgen excess, a key feature of PCOS, has a genetic component: the relationship of hyperandrogenemia to the development of insulin resistance requires further study. In conclusion, although similar insulin signalling defects have been identified in muscle and adipose tissue in PCOS and type 2 diabetes, these defects probably reflect a common final pathway resulting from genetic and environmental influences on insulin action that are unique to each disorder.