Expression of the functional leptin receptor mRNA in pancreatic islets and direct inhibitory action of leptin on insulin secretion

• Published in: Diabetes (New York, N.Y.) Vol. 46; no. 2; pp. 313 - 316
• Main Authors: EMILSSON, V, LIU, Y.-L, CAWTHORNE, M. A, MORTON, N. M, DAVENPORT, M
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.02.1997
• Subjects: Animals; Biological and medical sciences; Carrier Proteins - genetics; Cell receptors; Culture Techniques; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Gene Expression; Identification and classification; Insulin; Insulin - metabolism; Insulin Secretion; Islets of Langerhans - metabolism; Leptin; Medical sciences; Mice; Mice, Obese; Physiological aspects; Proteins - pharmacology; Rats; Rats, Mutant Strains; Receptors, Cell Surface; Receptors, Leptin; Recombinant Proteins - pharmacology; Secretory Rate - drug effects; Tissue Distribution; Endocrinopathy; Animal model; Obesity; Pancreatic hormone; Secretion; Diabetes mellitus; Rodentia; Peptide hormone; Langerhans islet; Gene expression; Hereditary; Insulin; Vertebrata; Experimental disease; Mammalia; Mouse; Leptin; Hormonal regulation; Endocrine pancreas; Hormonal receptor
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diab.46.2.313

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.