Rapid Publications Expression of the Functional Leptin Receptor mRNA in Pancreatic Islets and Direct Inhibitory Action of Leptin on Insulin Secretion

Leptin, encoded for by the mouse ob gene, regulates feeding behavior and energy metabolism. Its receptor (Ob-R) is encoded by the mouse diabetic (d&) gene and is mutated in the db/db mouse so that it lacks the cyto-plasmic domain. We show that the full-length leptin receptor (Ob-Rb), which is believed to transmit the lep-tin signal, is expressed in pancreatic islets of 06/06 and wild-type mice, as well as in hypothalamus, liver, kidney, spleen, and heart. Recombinant leptin inhibited basal insulin release in the perfused pancreas preparation from 06/06 mice but not in that from Zucker fa/fa rats. Leptin (1-100 nmol/1) also produced a dose-dependent inhibition of glucose-stimulated insulin secretion by isolated islets from 06/06 mice. In contrast, leptin at maximum effective concentration (100 nmol/1) did no