Stimulatory effect of xenin-8 on insulin and glucagon secretion in the perfused rat pancreas.
Xenin is a 25-amino acid peptide of the neurotensin/xenopsin family identified in gastric mucosa as well as in a number of tissues, including the pancreas of various mammals. In healthy subjects, plasma xenin immunoreactivity increases after meals. Infusion of the synthetic peptide in dogs evokes a rise in plasma insulin and glucagon levels and stimulates exocrine pancreatic secretion. The latter effect has also been demonstrated for xenin-8, the C-terminal octapeptide of xenin. We have investigated the effect of xenin-8 on insulin, glucagon and somatostatin secretion in the perfused rat pancreas. Xenin-8 stimulated basal insulin secretion and potentiated the insulin response to glucose in a dose-dependent manner (EC(50)=0.16 nM; R(2)=0.9955). Arginine-induced insulin release was also augmented by xenin-8 (by 40%; p<0.05). Xenin-8 potentiated the glucagon responses to both arginine (by 60%; p<0.05) and carbachol (by 50%; p<0.05) and counteracted the inhibition of glucagon release induced by increasing the glucose concentration. No effect of xenin-8 on somatostatin output was observed. Our observations indicate that the reported increases in plasma insulin and glucagon levels induced by xenin represent a direct influence of this peptide on the pancreatic B and A cells.
Silvestre
Ramona A
RA
Department of Physiology, Medical School, Hospital Universitario Puerta de Hierro, Universidad Autónoma de Madrid, Madrid, Spain. rsilvestre.hpth@salud.madrid.org
Rodríguez-Gallardo
Jovita
J
Egido
Eva M
EM
Hernández
Raquel
R
Marco
José
J
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005753:Gastric Mucosa / Q000378:metabolism; D005934:Glucagon / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D009496:Neurotensin; D010179:Pancreas / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000378:metabolism; D013997:Time Factors
D007328:Insulin; D010446:Peptide Fragments; D010455:Peptides; C483913:xenin-8; C077659:xenin 25; D009496:Neurotensin; D013004:Somatostatin; D002217:Carbachol; D005934:Glucagon; D001120:Arginine