LEPTIN - A POTENT INHIBITOR OF INSULIN-SECRETION

The hormone leptin is expressed and secreted by the adipose tissue and impacts on the central nervous system. Leptin is involved in the regu lation of energy balance, satiety, and body composition. The lack of a ctive leptin results in obesity, high food intake, hyperglycemia, and hyperinsulinemia, We present data supporting effects of leptin on the endocrine pancreas. We found the leptin receptor to be expressed in in sulin-and glucagon-secreting cells derived from mouse, hamster, and ra t pancreas. In the isolated perfused rat pancreas leptin is a potent i nhibitor of basal and glucose-induced insulin secretion, especially du ring the first phase of the insulin response. At isolated mouse islets and insulin-secreting INS-1 cells leptin reduced promptly and persist ently the intracellular Ca2+ levels. Cytoplasmic Ca2+ oscillation ampl itude was decreased and the oscillation frequency increased. These fin dings suggest functional active receptors for leptin on insulin-secret ing B-cells. Therefore, leptin is a metabolic hormone and not only a s ignal to the brain indicating filled fat stores. Our data suggest that leptin is also a signal back to the endocrine pancreas that no more i nsulin is required to replenish fat stores. Thus, an ''adipo-insular a xis'' operating with two arms exists: insulin and glucagon are signals to the adipocyte. This releases leptin, which could be the mediator o f the respective feedback to the pancreas. A defective leptin suppress ion of insulin secretion could contribute to hyperinsulinemia and dist urbances of glucose metabolism. (C) 1997 Elsevier Science Inc.