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

Lynda Whiting, Kevin W. Stewart, Deborah L. Hay, Paul W. Harris, Yee S. Choong, Anthony R J Phillips, Margaret A. Brimble, Garth J S Cooper

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12 Citations (Scopus)


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. Glicentinrelated 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.

Original languageEnglish
Article numbere12638
Number of pages12
JournalPhysiological Reports
Issue number12
Publication statusPublished - Dec 2015
Externally publishedYes


  • GLP-1
  • Glucagon
  • GRPP
  • GSIS
  • Proglucagon

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