Urocortin III is expressed in pancreatic β-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, Wylie Vale

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    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 β-cells and in a mouse β-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.

    Original languageEnglish (US)
    Pages (from-to)3216-3224
    Number of pages9
    JournalEndocrinology
    Volume144
    Issue number7
    DOIs
    StatePublished - Jul 1 2003

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    ASJC Scopus subject areas

    • Endocrinology

    Cite this

    Li, C., Chen, P., Vaughan, J., Blount, A., Chen, A., Jamieson, P. M., Rivier, J., Smith, M. S., & Vale, W. (2003). Urocortin III is expressed in pancreatic β-cells and stimulates insulin and glucagon secretion. Endocrinology, 144(7), 3216-3224. https://doi.org/10.1210/en.2002-0087