title: Expression of the functional leptin receptor mRNA in pancreatic islets and direct inhibitory action of leptin on insulin secretion.
abstract: Leptin, encoded for by the mouse ob gene, regulates feeding behavior and energy metabolism. Its receptor (Ob-R) is encoded by the mouse diabetic (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-Rb), which is believed to transmit the leptin signal, is expressed in pancreatic islets of ob/ob 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 ob/ob mice but not in that from Zucker fa/fa rats. Leptin (1-100 nmol/l) also produced a dose-dependent inhibition of glucose-stimulated insulin secretion by isolated islets from ob/ob mice. In contrast, leptin at maximum effective concentration (100 nmol/l) did not inhibit glucose-stimulated insulin secretion by islets from db/db mice. These results provide evidence that a functional leptin receptor is present in pancreatic islets and suggest that leptin overproduction, particularly from abdominal adipose tissue, may modify directly both basal and glucose-stimulated insulin secretion.
authors.affiliation: Clore Laboratory, University of Buckingham, U.K.
authors.forename: V
authors.initials: V
authors.lastname: Emilsson
authors.forename: Y L
authors.initials: YL
authors.lastname: Liu
authors.forename: M A
authors.initials: MA
authors.lastname: Cawthorne
authors.forename: N M
authors.initials: NM
authors.lastname: Morton
authors.forename: M
authors.initials: M
authors.lastname: Davenport
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D046508:Culture Techniques; D015870:Gene Expression; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D020738:Leptin; D051379:Mice; D008820:Mice, Obese; D011506:Proteins / Q000494:pharmacology; D051381:Rats; D011922:Rats, Mutant Strains; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D011994:Recombinant Proteins / Q000494:pharmacology; D012636:Secretory Rate / Q000187:drug effects; D014018:Tissue Distribution
chemical_list: D002352:Carrier Proteins; D007328:Insulin; D020738:Leptin; D011506:Proteins; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D011994:Recombinant Proteins; C515447:leptin receptor, mouse