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 pM 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.(ABSTRACT TRUNCATED AT 250 WORDS)