Adipocytokines and insulin resistance.

Abstract

Insulin resistance is defined as a failure of target organs to respond normally to the action of insulin. Insulin resistance causes incomplete suppression of hepatic glucose output and impaired insulin-mediated glucose uptake in the periphery (skeletal muscle and adipose), leading to increased insulin requirements. When increased insulin requirements are not matched by increased insulin levels, hyperglycemia develops. Insulin resistance is also known to be associated with other conditions such as central obesity, hypertension, and dyslipidemia, all risk factors for cardiovascular disease. The constellation of these metabolic abnormalities has been termed the metabolic syndrome. Obesity is a well-recognized risk factor for the development of insulin resistance and the metabolic syndrome. In addition to total amount of fat, distribution of adipose tissue is also important, with visceral depots contributing more to insulin resistance. The mechanisms by which accumulation and anatomic distribution of adipose tissue may be related to the development of insulin resistance are under intense investigation. Adipose tissue has traditionally been considered an energy storage organ, but over the last decade, a novel role of the adipose tissue as an endocrine organ has emerged (1). Adipose tissue is currently known to secrete a large number of factors with diverse functions. These factors include free fatty acids (FFA) with well described physiological and pathophysiological effects on glucose homeostasis (2), and proteins, termed adipocytokines, that act in an autocrine, paracrine, or endocrine fashion to control various metabolic functions (Table 1). Some of these adipocytokines have been implicated in the development of insulin resistance. They may act locally or distally to alter insulin sensitivity in insulin-targeted organs such as muscle and liver or may act through neuroendocrine, autonomic, or immune pathways. Here, we focus on certain adipocytokines and how they influence insulin sensitivity. We review potential insulin sensitizers such as leptin and adiponectin or insulin antagonists such as resistin, TNF, and IL-6. Leptin