Glucose-dependent insulinotropic polypeptide augmentation of insulin. Physiology or pharmacology?

Glucose-dependent insulinotropic polypeptide (GIP) is said to be a major physiologic factor in the augmentation of the insulin response to oral glucose. Whether GIP promotes insulin release at physiologic concentrations of glucose or GIP, however, is questionable. To investigate this further, volunteers were infused with 10, 20, or 40 g intravenous (i.v.) glucose, with or without simultaneous GIP infusion, to produce plasma levels of GIP or glucose similar to those seen after oral glucose. The effect of 40 g i.v. glucose with three times the original dose of GIP was also investigated. No significant enhancement of glucose-stimulated insulin secretion was seen when GIP was infused with 10 or 20 g i.v. glucose; however, with 40 g a doubling of the insulin response occurred. The higher dose of GIP caused a further increase in insulin response (30-min increment, 972 +/- 191 pmol/L; compared with glucose alone, 356 +/- 100 pmol/L, P less than 0.01; and compared with low GIP, 602 +/- 247 pmol/L, P less than 0.02). The glucose increment after the 40-g i.v. dose was +9.2 mmol/L. The concentration of GIP and glucose required to produce significant potentiation of the insulin response appears to be in the pharmacologic, rather than physiologic, range.