13 - Role of hyperinsulinemic insulin resistance in polycystic ovary syndrome

Summary

Introduction

Hyperinsulinemic insulin resistance is now recognized as a prominent feature of polycystic ovary syndrome (PCOS). Only recently has its role in the pathophysiology of PCOS been recognized. Both obese and lean women with PCOS appear to have some degree of insulin resistance and understanding the role of insulin resistance in PCOS has led to the successful use of insulin sensitizing drugs in the treatment of this disorder.

Insulin resistance is defined as the reduced ability of insulin to stimulate glucose uptake. Insulin actually has a number of subcellular actions not related to glucose uptake Figure 13.1 below outlines two major pathways of insulin subcellular signaling. Clinically, insulin stimulation of the GLUT-4 transporter increases glucose uptake intracellularly (Sivitz et al. 1989, Douen et al. 1990, Klip and Paquet 1990, Koranyi et al. 1990). However, a number of additional subcellular insulin signaling pathways also exist, such as the mitogen activated protein (MAP) kinase activation pathway that primarily regulate mitogenesis. In vitro data in a number of different cellular models of insulin resistance and diabetes have demonstrated that while glucose uptake is relatively downregulated in insulin resistance, MAP kinase pathways and alternate pathways may be upregulated leading to increased de novo lipogenesis in type 2 diabetes mellitus (Nikoulina et al. 2001, Bouzakri et al. 2003, Carlson et al. 2003, Koistinen et al. 2003). Therefore, generally when defining insulin resistance, it becomes necessary to specify that decreased insulin mediated intracellular uptake of glucose is the “resistant” pathway of insulin action.