Contribution of adipocyte-derived factors to beta-cell dysfunction in diabetes

In addition to serving as an energy reservoir, the adipocyte has been characterized as an endocrine cell, secreting many bioactive factors which influence energy homeostasis. Being overweight, with excessive adipose tissue, is considered to be part of the pathogenesis of type 2 diabetes. Insulin resistance and beta-cell dysfunction are two major pathophysiological changes seen in type 2 diabetes. In addition to inducing insulin resistance in insulin-responsive tissues, adipocyte-derived factors play an important role in the pathogenesis of beta-cell dysfunction. Leptin, free fatty acids, adiponectin, tumor necrosis factor-alpha and interleukin-6 are all produced and secreted by adipocytes, and may directly influence aspects of beta-cell function, including insulin synthesis and secretion, insulin cell survival and apoptosis. During the progression from normal weight to obesity and on to overt diabetes, the adipocyte-derived factors contribute to the occurrence and development of beta-cell dysfunction and type 2 diabetes.