Effects of leptin on insulin secretion from isolated rat pancreatic islets.

Leptin is a hormone secreted by adipocytes as a peripheral metabolic signal for the central regulation of energy homeostasis or the reproductive system. Recent studies demonstrated that leptin receptor mRNA is expressed in pancreatic islets of rodents and that leptin at relatively high doses inhibits glucose-induced insulin secretion from rat islets. However, the physiological mechanism of leptin on insulin secretion has not been identified. In this study, we report that leptin inhibits glucose-induced insulin secretion at lower concentrations ranging from 25 to 50 ng/ml using a static incubation method. A perifusion study revealed that leptin (50 ng/ml) affected the second phase of insulin secretion but not the first phase. Leptin did not affect insulin secretion stimulated by glibenclamide (1 and 5 micromol/l) or forskolin (1 micromol/l). Leptin (50 ng/ml) significantly inhibited insulin secretion induced by the phorbol ester phorbol 12-myristate 13-acetate (TPA) in the presence of Ca2+ but not in the absence of Ca2+. Because TPA is known to activate protein kinase C (PKC), these present results suggest that leptin, at a physiological concentration, suppresses the second phase of insulin secretion by reducing activity of the Ca2+-dependent PKC isoform.