Glucose-dependent insulinotropic hormone potentiates the hypoglycemic effect of glibenclamide in healthy volunteers: Evidence for an effect on insulin extraction

Glucose-dependent insulinotropic hormone (GIP) is an intestinal hormone con sidered to be an important mediator of the incretin effect, i.e. the augmen ted insulin release observed in response to orally, compared with iv, admin istered glucose, despite isoglycemic glucose profiles. Stimulation of beta -cell secretion of insulin by GIP is seen both in vitro and in vivo at perm issive extracellular glucose concentrations (>6 mmol/L). It has also been c laimed that part of the incretin effect is due to decreased insulin extract ion. We now show that an infusion of GIP in healthy volunteers in whom bloo d glucose levels were maintained at 5 mmol/L, increased glibenclamide-stimu lated. levels of plasma insulin without significantly changing the C peptid e profile. The increased plasma insulin levels necessitated extra glucose i nfusion to maintain euglycemia, demonstrating the biological significance o f the elevated insulin levels. Infusion of GIP alone caused neither glucose changes nor elevation of C peptide or insulin levels. Hence, our results s how that at a blood glucose concentration of 5 mmol/L, GIP augments the inc rease in plasma insulin levels stimulated by glibenclamide, possibly acting through a mechanism involving decreased insulin extraction in the liver or peripheral tissues, thus increasing insulin availability.