FEEDBACK-REGULATION OF GLUCOSE-DEPENDENT INSULINOTROPIC POLYPEPTIDE (GIP) SECRETION BY INSULIN IN CONSCIOUS RATS

Feedback regulation of glucose-dependent insulinotropic polypeptide (GIP) was studied in a conscious rat model. Male Wistar rats were preconditioned to partial restraint, the tail artery and vein were cannulated under local anesthesia. All animals received 1 g/kg oral glucose by gavage and were divided into 3 groups: One group ('euglycemic hyperinsulinemic', EH) underwent rapid induction of hyperinsulinemia by i.v. insulin infusion from 5 min prior to oral glucose until 120 min after (mean plasma insulin = 2285 +/- 108 pM +/- S.E.M., n = 5); a second group ('hyperglycemic hyperinsulinemic', HH) underwent rapid induction of both hyperinsulinemia and hyperglycemia (mean serum glucose = 12.9 +/- 0.4 mM +/- S.E.M., mean plasma insulin 3160 +/- 109 pM, n = 5). A third group ('control') underwent saline infusion alone (n = 5). Arterial blood was collected for GIP estimation at -10, 0, 10, 20, 30, 50, 70, 90 and 120 min after oral glucose. In the control group GIP rose by 96% from a mean basal concentration of 114 +/- 12 pM to a peak of 224 +/- 14 phl by 20 min, and returned to baseline within 70 min. In EH, the GIP rise was blunted and the peak (146 +/- 31 pM) occurred at 10 min, while in HH GIP peaked at 192 +/- 32 pM 10 min after oral glucose (a 92% increase over basal). Compared to controls, total area under the curve for GIP was less for EH (598 +/- 112 versus 971 +/- 94 pmol/l/h +/- S.E.M., P<0.034). GIP response in HH was similar to the control group at 853 +/- 134 pmol/l/h. These data indicate that the GIP response to oral glucose is suppressed by hyperinsulinemia in the conscious rat, but that this suppression is attenuated when hyperinsulinemia is accompanied by hyperglycemia. Thus insulin, and not glucose, may provide feedback regulation of GIP secretion in the rat in vivo after oral glucose administration.