Oxyntomodulin inhibits pancreatic secretion through the nervous system in rats

Glicentin (GLIC), oxyntomodulin (OXM), and peptide YY (PYY) released in blo od by ileocolonic L-cells after meals may inhibit pancreatic secretion. Whe reas OXM interacts with glucagon and tCLP-1 receptors, OXM 19-37, a biologi cally active fragment, does not. The purpose of this study was to measure t he effect of OXM, OXM 19-37, GLIC, tGLP-1, and PYY on pancreatic secretion stimulated by 2 deoxyglucose (2DG), electrical stimulation of the vagus ner ves (VES), acetylcholine and cholecystokinin octapeptide (CCK8) in anesthet ized rats. The effect of OXM was also studied in dispersed pancreatic acini . Plasma oxyntomodulin-like immunoreactivity (OLI) was measured by radioimm unoassay after the exogenous infusion of OXM and after an intraduodenal mea l. OXM 19-37, infused at doses mimicking postprandial plasma levels of OLI, decreased pancreatic secretion stimulated by 2DG, VES, or CCK8. Similar ef fects were found with OXM and GLIC. OXM 19-37 did not change the pancreatic stimulation induced by acetylcholine in vivo, or CCK-induced amylase relea se in isolated acini. Vagotomy completely suppressed the inhibitory effect of OXM 19-37 on CCK8-stimulated pancreatic secretion. PW inhibited the effe ct of 2DG, but not that of CCK8, whereas tGLP-1, even in pharmacologic dose s, had no effect on stimulated pancreatic secretion. OXM, OXM 19-37, but no t tGLP-1, inhibit pancreatic secretion at physiologic doses, through a vaga l neural indirect mechanism, different from that used by PYY, and probably through a GLIC-related peptide-specific receptor.