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.