Lewis, K. et al. Proc. Natl. Acad. Sci. USA 98, 7570-7575, 2001 (June 19)
Hsu, S.Y. & Hsueh, A.J.W. Nature Medicine, 7 605-611, 2001
Review by Jun Yang on June 21, 2001
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 ofglucagon and insulin secretion.
Chien Li, et al. Endocrinology Vol. 2003,144(7), 3216-3224
Corticotropin-releasing factor (CRF) has been hypothesized to modulate consummatory behavior through the Type 2 CRF (CRF(2)) receptor. However, behavioral functions subserved by the CRF(2) receptor remain poorly understood. Recently, human urocortin II (hUcn II), a selective CRF(2) receptor agonist, was identified. To study the effects of this neuropeptide on ingestive behavior, we examined the effects of centrally infused hUcn II (i.c.v. 0, 0.01, 0.1, 1.0, 10.0 &mgr;g) on the microstructure of nose-poke responding for food and water in nondeprived, male rats. Malaise-inducing properties of the peptide were monitored using conditioned taste aversion (CTA) testing. To identify potential sites of action, central induction of Fos protein expression was examined. hUcn II dose dependently reduced the quantity and duration of responding for food and water at doses lower (0.01-1.0 &mgr;g) than that forming a CTA (10 &mgr;g). Effects were most evident during hours 4 to 6 of the dark cycle. Meal pattern analysis showed that hUcn II potently (0.1 &mgr;g) increased the satiating value of food. Rats ate and drank smaller and shorter meals without changing meal frequency. Rats also ate more slowly. hUcn II induced Fos in regions involved in visceral sensory processing and autonomic/neuroendocrine regulation and resembling those activated by appetite suppressants. hUcn II is a promising neuropeptide for investigating the role of the CRF(2) receptor in ingestive behavior.
Inoue K,et al. J Pharmacol Exp Ther 2003 Apr 1;305(1):385-393