TY - JOUR
T1 - Glicentin-related pancreatic polypeptide inhibits glucose-stimulated insulin secretion from the isolated pancreas of adult male rats
AU - Whiting, Lynda
AU - Stewart, Kevin W.
AU - Hay, Deborah L.
AU - Harris, Paul W.
AU - Choong, Yee S.
AU - Phillips, Anthony R J
AU - Brimble, Margaret A.
AU - Cooper, Garth J S
PY - 2015/12
Y1 - 2015/12
N2 - 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.
AB - 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.
KW - GLP-1
KW - Glucagon
KW - GRPP
KW - GSIS
KW - Proglucagon
UR - http://www.scopus.com/inward/record.url?scp=84964073952&partnerID=8YFLogxK
U2 - 10.14814/phy2.12638
DO - 10.14814/phy2.12638
M3 - Article
AN - SCOPUS:84964073952
SN - 2051-817X
VL - 3
JO - Physiological Reports
JF - Physiological Reports
IS - 12
M1 - e12638
ER -
