Enhancement of insulin secretory response to glucose-dependent insulinotropic polypeptide (GIP) by growth hormone in dogs.

In the present work we examined the incretin role of gut glucose-dependent insulinotropic polypeptide (GIP) in the insulin over-response to meal ingestion found in states of hypersomatotrophism. In this context, we studied IRI secretion after i.v. infusion of glucose alone (0.6 g/kg/h) and also combined with GIP (0.4 microgram/kg/h) in dogs during the control period and after subcutaneous administration of bovine growth hormone (bGH, 1 mg/kg), in randomized experiments at fortnightly intervals. Plasma levels of immunoreactive b-GH (IR-bGH) showed a comparable elevation at 24 h from each bGH injection. Coinciding with this rise, fasting plasma glucose was within the normal range and basal plasma levels of immunoreactive GIP (IR-GIP) remained unchanged. When GIP was given, there was a significant increase in IR-GIP plasma levels after 10 min of infusion, to a plateau near 200 pmol/l; the values were not influenced by concurrent administration of glucose with or without prior treatment with bGH. In the control observations, glucose infusion caused an insulin response area (IRA, pmol.min.l-1) of 3150 +/- 733. When GIP was co-infused with glucose, the IRA was enhanced to 6203 +/- 1380, p < 0.005. After the administration of bGH, the infusion of glucose alone increased the IRA to 9580 +/- 1446 (p < 0.001) and to 15,906 +/- 2943 (p < 0.001) when GIP was co-infused with glucose. The data suggest that in this state of high circulating levels of growth hormone of short duration, the secretion of insulin in response to the stimulus of glucose alone and also combined with GIP is clearly enhanced. The findings therefore lend support for the explanation of the high insulin secretion evoked by food intake in growth hormone-treated dogs.