Peptide YY (PYY) is released from the gut after ingestion of fat or after a meal. The purpose of this investigation was to examine the effect of PYY on gastric inhibitory polypeptide (GIP)-stimulated insulin release in conscious dogs with gastric and duodenal fistulas. In control experiments, 6 dogs received GIP (400 pmol/kg, i.v., for 1 h) and glucose (0.6 g/kg, i.v., for 1 h); the integrated insulin response over a 1-h period was 142 ± 32.7 ng-60 min/ml. The plasma GIP levels achieved by this procedure were similar to those observed by intraduodenal infusion of Lipomul (2 ml/min), suggesting that the dose of GIP used was within the physiologic range. Intravenous infusion of three different doses of PYY (100, 200, or 400 pmol/kg · h) caused a significant inhibition of insulin release stimulated by GIP + glucose; the integrated insulin response was reduced to 105, 88, and 79 ng-60 min/ml, respectively. On the other hand, PYY (400 pmol/ kg · h) had no effect on insulin secretion induced by intravenous glucose (0.6 g/kg · h) alone. These results indicate that PYY specifically inhibits the insulinotropic action of GIP and that PYY may play a negative-feedback regulatory role in the enteroinsular axis.
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