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Oxyntomodulin inhibits pancreatic secretion through the nervous system in rats
Y Anini1, C Jarrousse, J Chariot
1INSERM U410, Faculté de Médecine X. Bichat, Paris, France.
Abstract:
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.
Insights
Oxyntomodulin (OXM) and its fragment OXM 19-37 inhibit pancreatic secretion via a vagal pathway, unlike peptide YY (PYY) or tGLP-1. Glicentin (GLIC) also showed inhibitory effects on pancreatic function.
Area of Science:
- Gastroenterology
- Endocrinology
- Neuroscience
Background:
- Glicentin (GLIC), oxyntomodulin (OXM), and peptide YY (PYY) are gut hormones released post-meal that may suppress pancreatic secretion.
- While OXM targets glucagon and tGLP-1 receptors, its active fragment OXM 19-37 does not.
Purpose of the Study:
- To investigate the effects of OXM, OXM 19-37, GLIC, tGLP-1, and PYY on pancreatic secretion.
- To determine the mechanisms of inhibition, including vagal nerve involvement and receptor specificity.
Main Methods:
- Pancreatic secretion was stimulated using 2-deoxyglucose (2DG), vagal nerve electrical stimulation (VES), acetylcholine, and cholecystokinin octapeptide (CCK8) in anesthetized rats.
- Exogenous OXM and intraduodenal meals were used to measure plasma OLI via radioimmunoassay.
- Studies were also conducted in dispersed pancreatic acini and with vagotomy.
Main Results:
- OXM 19-37, at physiological levels, reduced pancreatic secretion stimulated by 2DG, VES, and CCK8.
- OXM and GLIC demonstrated similar inhibitory effects.
- OXM 19-37's inhibition of CCK8-stimulated secretion was abolished by vagotomy, suggesting a vagal mechanism.
- PYY inhibited 2DG-stimulated secretion but not CCK8-stimulated secretion.
- tGLP-1 had no effect on stimulated pancreatic secretion.
Conclusions:
- OXM and OXM 19-37 inhibit pancreatic secretion at physiological doses via an indirect vagal neural mechanism.
- This mechanism differs from that of PYY and likely involves a GLIC-related peptide-specific receptor.
- tGLP-1 does not appear to play a significant role in inhibiting stimulated pancreatic secretion through this pathway.