Glicentin‐related pancreatic polypeptide inhibits glucose‐stimulated insulin secretion from the isolated pancreas of adult male rats

Physiological Reports

Lynda Whiting¹  Kevin W. Stewart¹  Deborah L. Hay¹  Paul W. Harris²  Yee S. Choong¹  Anthony R. J. Phillips¹  Margaret A. Brimble² 

[1] School of Biological Sciences, University of Auckland, Auckland, New Zealand;The Maurice Wilkins Centre for Molecular BioDiscovery, New Zealand

关键词: GLP‐1;    glucagon;    GRPP;    GSIS;    proglucagon;   

DOI  :  10.14814/phy2.12638

来源: Wiley

【 摘 要 】

Abstract

Peptides derived from the glucagon gene Gcg, for example, glucagon and glucagon-like peptide 1 (GLP-1), act as physiological regulators of fuel metabolism and are thus of major interest in the pathogenesis of diseases, such as type-2 diabetes and obesity, and their therapeutic management. Glicentin-related pancreatic polypeptide (GRPP) is a further, 30 amino acid Gcg-derived peptide identified in human, mouse, rat, and pig. However, the potential glucoregulatory function of this peptide is largely unknown. Here, we synthesized rat GRPP (rGRPP) and a closely related peptide, rat GRPP-like peptide (rGRPP-LP), and investigated their actions in the liver and pancreas of adult male rats by employing isolated-perfused organ preparations. Rat GRPP and rGRPP-LP did not affect glucose output from the liver, but both elicited potent inhibition of glucose-stimulated insulin secretion (GSIS) from the rat pancreas. This action is unlikely to be mediated by glucagon or GLP-1 receptors, as rGRPP and rGRPP-LP did not stimulate cyclic adenosine monophosphate (cAMP) production from the glucagon or GLP-1 receptors, nor did they antagonize glucagon- or GLP-1-stimulated cAMP-production at either receptor. GRPP and GRPP-LP may be novel regulators of insulin secretion, acting through an as-yet undefined receptor.

【 授权许可】

CC BY   
© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

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