Comparison of the postprandial release of peptide YY and proglucagon-derived peptides in the rat

Endocrine L-cells of the distal intestine synthesize both peptide YY (PYY) and proglucagon-derived peptides (PGDPs), whose release has been reported t o be either parallel or selective. Here we compare the release mechanisms o f PYY, glucagon-like peptide-1 (GLP-1), and oxyntomodulin-like immunoreacti vity (OLI) in vivo. Anaesthetized rats were intraduodenally (ID) given eith er a mixed semi-liquid meal or oleic acid, or they received oleic acid or s hort chain fatty acids (SCFA) intra-colonically (IC). The ID meal released the three peptides with a similar time-course (peak at 30 min); ID oleic ac id produced a progressive release of PYY and OLI, while GLP-1 release was l ess. IC oleic acid or SCFA released smaller (but significant) amounts of PY Y but no OLI or GLP-1. Hexamethonium inhibited most of the response to the ID meal and ID oleic acid, but did not change the PYY response to IC oleic acid. NG-nitro-L-arginine methyl ester (L-NAME, a nitric oxide synthase inh ibitor) inhibited meal-induced PYY release and left OLI and GLP-1 unaffecte d. BW10 (a gastrin-releasing peptide antagonist) had no effect on the meal- induced release of either peptide. These results suggest a parallel initial release of PYY, OLI and GLP-1 after the ID meal, or oleic acid, by an indi rect mechanism triggered in the proximal bowel, using nicotinic synapses, a nd involving nitric oxide release for PYY and an unknown mediator for PGDPs . For PYY there is a later phase of peptide release, probably induced by di rect contact between nutrients and colonic L-cells.