title: Urocortin III is expressed in pancreatic beta-cells and stimulates insulin and glucagon secretion.
abstract: 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 beta-cells and in a mouse beta-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, astressin(2)-B. Furthermore, Ucn III stimulated glucagon and insulin release from isolated rat islets, and astressin(2)-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.
authors.affiliation: Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Chien
authors.initials: C
authors.lastname: Li
authors.forename: Peilin
authors.initials: P
authors.lastname: Chen
authors.forename: Joan
authors.initials: J
authors.lastname: Vaughan
authors.forename: Amy
authors.initials: A
authors.lastname: Blount
authors.forename: Alon
authors.initials: A
authors.lastname: Chen
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Jamieson
authors.forename: Jean
authors.initials: J
authors.lastname: Rivier
authors.forename: M Susan
authors.initials: MS
authors.lastname: Smith
authors.forename: Wylie
authors.initials: W
authors.lastname: Vale
mesh_terms: D000818:Animals; D002460:Cell Line; D003346:Corticotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D005934:Glucagon / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D054832:Urocortins
chemical_list: C101531:CRF receptor type 2; D007328:Insulin; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D005934:Glucagon; D003346:Corticotropin-Releasing Hormone