Glucose-Dependent Insulinotropic Polypeptide A Bifunctional Glucose-Dependent Regulator of Glucagon and Insulin Secretion in Humans

OBJECTIVE—To evaluate the glucose dependency of glucose-dependent insulinotropic polypeptide (GIP) effects on insulin and glucagon release in 10 healthy male subjects ([means 6 SEM] aged 23 6 1 years, BMI 23 6 1 kg/m2, and HbA1c 5.5 6 0.1%). RESEARCH DESIGN ANDMETHODS—Saline or physiological doses of GIP were administered intravenously (randomized and double blinded) during 90 min of insulin-induced hypoglycemia, euglycemia, or hyperglycemia. RESULTS—During hypoglycemia, GIP infusion caused greater glucagon responses during the first 30 min compared with saline (76 6 17 vs. 28 6 16 pmol/L per 30 min, P, 0.008), with similar peak levels of glucagon reached after 60 min. During euglycemia, GIP infusion elicited larger glucagon responses (626 18 vs.2116 8 pmol/L per 90 min, P, 0.005). During hyperglycemia, compa-rable suppression of plasma glucagon (24616 81 vs.23716 5