Physiological and pathophysiological regulation of regional adipose tissue in the development of insulin resistance and type 2 diabetes

Abstract

To survey the latest state of knowledge concerning the regulation of regional adipocytes and their role in the development of insulin resistance and type 2 diabetes. Data from the English-language literature on regional adipocytes, including abdominal, intramyocellular, intrahepatic and intra-islet fat as well as the adipokines and their relations to insulin resistance and type 2 diabetes, were reviewed. It is not the total amount of fat but the fat that resides within skeletal muscle cell (intramyocellular fat), hepatocytes and intra-abdominally (visceral fat), via systemic and local secretion of several adipokines, that influences insulin resistance. Among the adipokines that relate to insulin resistance, adiponectin and leptin appear to have clinical relevance to human insulin resistance and others may also contribute, but their role is still inconclusive. The intra-islet fat also adversely affects beta-cell function and number (beta-cell apoptosis), eventually leading to deterioration of glucose tolerance. The abnormal location of fat observed in patients with type 2 diabetes and their relatives is conceivably partly the results of the genetically determined, impaired mitochondrial fatty acid oxidative capacity. Restriction or elimination of the fat load by weight control, regular exercise and thiazolidinediones has been shown to improve insulin resistance and beta-cell function and to delay the development of type 2 diabetes. These data support the plausibility of an essential role of regional adipose tissue in the development of insulin resistance and type 2 diabetes.