Oxyntomodulin inhibits pancreatic secretion through the nervous system in rats.
Glicentin (GLIC), oxyntomodulin (OXM), and peptide YY (PYY) released in blood by ileocolonic L-cells after meals may inhibit pancreatic secretion. Whereas OXM interacts with glucagon and tGLP-1 receptors, OXM 19-37, a biologically active fragment, does not. The purpose of this study was to measure the effect of OXM, OXM 19-37, GLIC, tGLP-1, and PYY on pancreatic secretion stimulated by 2 deoxyglucose (2DG), electrical stimulation of the vagus nerves (VES), acetylcholine and cholecystokinin octapeptide (CCK8) in anesthetized rats. The effect of OXM was also studied in dispersed pancreatic acini. Plasma oxyntomodulin-like immunoreactivity (OLI) was measured by radioimmunoassay after the exogenous infusion of OXM and after an intraduodenal meal. OXM 19-37, infused at doses mimicking postprandial plasma levels of OLI, decreased pancreatic secretion stimulated by 2DG, VES, or CCK8. Similar effects were found with OXM and GLIC. OXM 19-37 did not change the pancreatic stimulation induced by acetylcholine in vivo, or CCK-induced amylase release in isolated acini. Vagotomy completely suppressed the inhibitory effect of OXM 19-37 on CCK8-stimulated pancreatic secretion. PYY inhibited the effect of 2DG, but not that of CCK8, whereas tGLP-1, even in pharmacologic doses, had no effect on stimulated pancreatic secretion. OXM, OXM 19-37, but not tGLP-1, inhibit pancreatic secretion at physiologic doses, through a vagal neural indirect mechanism, different from that used by PYY, and probably through a GLIC-related peptide-specific receptor.
Anini
Y
Y
INSERM U410, Faculté de Médecine X. Bichat, Paris, France.
Jarrousse
C
C
Chariot
J
J
Nagain
C
C
Yanaihara
N
N
Sasaki
K
K
Bernad
N
N
Le Nguyen
D
D
Bataille
D
D
Rozé
C
C
D000818:Animals; D003847:Deoxyglucose / Q000494:pharmacology; D004347:Drug Interactions; D053771:Glicentin; D005934:Glucagon / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides / Q000097:blood / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D053772:Oxyntomodulin; D010179:Pancreas / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism*; D010446:Peptide Fragments / Q000097:blood / Q000494:pharmacology; D019894:Peptide YY / Q000097:blood / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012844:Sincalide / Q000494:pharmacology; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
D053772:Oxyntomodulin; D010446:Peptide Fragments; D011498:Protein Precursors; C081298:oxyntomodulin (19-37); D019894:Peptide YY; D004763:Glucagon-Like Peptides; D053771:Glicentin; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D003847:Deoxyglucose; D012844:Sincalide