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Endocrinology, doi:10.1210/en.2002-0087
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Endocrinology Vol. 144, No. 7 3216-3224
Copyright © 2003 by The Endocrine Society

Urocortin III Is Expressed in Pancreatic ß-Cells and Stimulates Insulin and Glucagon Secretion

Chien Li, Peilin Chen, Joan Vaughan, Amy Blount, Alon Chen, Pauline M. Jamieson, Jean Rivier, M. Susan Smith and Wylie Vale

Clayton Foundation Laboratories for Peptide Biology (C.L., J.V., A.B., A.C., P.M.J., J.R., W.V.), Salk Institute for Biological Studies, La Jolla, California 92037; Oregon National Primate Research Center, Department of Physiology and Pharmacology (P.C., M.S.S.), Oregon Health & Sciences University, Beaverton, Oregon 97006

Address all correspondence and requests for reprints to: Wylie W. Vale, Ph.D., The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037. E-mail: vale{at}salk.edu.

Urocortin (Ucn) III, or stresscopin, is a high affinity ligand for the type 2 corticotropin-releasing factor (CRFR2) receptor recently identified in rodents and human. Ucn III was initially identified as a neuropeptide expressed in discrete areas in the brain. In the present study, we demonstrate that Ucn III is expressed in pancreatic ß-cells and in a mouse ß-cell line, MIN6. Ucn III secretion from the cells was measured using a highly specific RIA, and we found that high potassium, forskolin, or high glucose can stimulate Ucn III secretion from these cells. In vivo studies showed that rats receiving an iv Ucn III injection had a significant elevation of plasma glucagon followed by plasma glucose levels compared with rats receiving vehicle. Ucn III injections also result in an increase in plasma insulin levels. The observed effects of Ucn III were blocked by pretreatment with a CRFR2 antagonist, astressin2-B. Furthermore, Ucn III stimulated glucagon and insulin release from isolated rat islets, and astressin2-B abolished the effects of Ucn III, in keeping with a CRFR2-mediated mechanism. Taken together, the present studies suggest pancreatic Ucn III acting through CRFR2 is involved in the local regulation of glucagon and insulin secretion.




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