Chapter 10 - Obesity and insulin resistance: pathophysiology guiding precision therapy

Abstract

This chapter provides an overview of the role of insulin resistance in human disease. The genetics and the pathophysiology of insulin action in the liver, fat, and muscle are discussed. In obesity and type 2 diabetes, the ability of insulin to suppress adipocyte lipolysis, hepatic gluconeogenesis, and glycogenolysis, whereas insulin-mediated stimulation of glucose uptake by skeletal muscle is reduced. The current data point to a functional defect in hepatic glucokinase activity as a key driver of hepatic insulin resistance. The role of glucagon in the regulation of glucose metabolism is also considered. These pathophysiological insights provide the basis for nonpharmacological and pharmacological therapeutic interventions.