EFFECTS OF GLUCAGON-LIKE PEPTIDE-1 (7-36 AMIDE) ON GLUCOSE KINETICS DURING SOMATOSTATIN-INDUCED SUPPRESSION OF INSULIN-SECRETION IN HEALTHY-MEN

Glucagon-like peptide 1 (GLP-1) is known to stimulate insulin secretio n and biosynthesis, but has also been shown to decrease insulin requir ements in type 1 diabetic subjects suggesting insulin-independent effe cts. To assess whether GLP-1 exerts also direct effects on whole-body glucose metabolism, 6,6-D-2-glucose kinetics were measured in 8 health y volunteers receiving once GLP-1, once saline during hyperglycemic gl ucose clamping, while somatostatin with replacement amounts of insulin , glucagon and growth hormone was infused. Even though endogenous insu lin secretion could not be blocked completely (increased plasma concen trations of C-peptide and proinsulin), somatostatin infusion resulted in stable insulin and glucagon plasma levels in both protocols (GLP-1 vs, placebo: NS). After 3 h of GLP-1 infusion, peripheral glucose disa ppearance significantly increased compared to placebo (p < 0.03) despi te of somatostatin-induced suppression of insulin and glucagon secreti on. Thus, GLP-1 infusion seems to have direct stimulatory effects on p eripheral glucose metabolism in man.