Effect of Intravenous Infusion of Exenatide (Synthetic Exendin-4) on Glucose-Dependent Insulin Secretion and Counterregulation During Hypoglycemia

This study assessed whether glucose-dependent insulin secretion and overall counterregulatory response are preserved during hypoglycemia in the presence of ex-enatide. Twelve healthy fasted volunteers were random-ized in a triple-blind crossover study to receive either intravenous exenatide (0.066 pmol kg1 min1) or placebo during a 270-min stepwise hyperinsulinemic-hypoglycemic clamp (insulin infusion 0.8 mU kg1 min1). Plasma glucose was clamped sequentially at 5.0 (0–120 min), 4.0 (120–180 min), 3.2 (180–240 min), and 2.7 mmol/l (240–270 min). At 270 min, insulin infusion was terminated and plasma glucose increased to 3.2 mmol/l. The time to achieve plasma glucose>4 mmol/l thereafter was recorded. Insulin secretory rates (ISRs) and counterregulatory hormones were measure