EXPRESSION OF THE FUNCTIONAL LEPTIN RECEPTOR MESSENGER-RNA IN PANCREATIC-ISLETS AND DIRECT INHIBITORY-ACTION OF LEPTIN ON INSULIN-SECRETION

Leptin, encoded for by the mouse ob gene, regulates feeding behavior a nd energy metabolism. Its receptor (Ob-R) is encoded by the mouse diab etic (db) gene and is mutated in the db/db mouse so that it lacks the cytoplasmic domain. We show that the full-length leptin receptor (Ob-R b), which is believed to transmit the leptin signal, is expressed in p ancreatic islets of ob/ob and wild-type mice, as well as in hypothalam us, liver, kidney, spleen, and heart. Recombinant leptin inhibited bas al insulin release in the perfused pancreas preparation from ob/ob mic e but not in that from Zucker fa/fa rats. Leptin (1-100 nmol/l) also p roduced a dose-dependent inhibition of glucose-stimulated insulin secr etion by isolated islets from ob/ob mice. In contrast, leptin at maxim um effective concentration (100 nmol/l) did not inhibit glucose-stimul ated insulin secretion by islets from db/db mice. These results provid e evidence that a functional leptin receptor is present in pancreatic islets and suggest that leptin overproduction, particularly from abdom inal adipose tissue, may modify directly both basal and glucose-stimul ated insulin secretion.