GLP-1 receptor blockade reduces stimulated insulin secretion
A cross-over study in which subjects received either a DPP4 inhibitor (DPP4i; sitagliptin) or placebo on two separate days. On each day they received a bolus of intravenous (IV) arginine during sequential 60-minute infusions of the GLP-1r blocker exendin[9-39] (Ex-9) and saline. Plasma GLP-1 remained at fasting levels throughout the experiments and IV arginine stimulated both ?- and ?-cell secretion in all subjects. Ex-9 infusion reduced C-PArg in both the diabetic and nondiabetic groups by ~14% (p < 0.03 for both groups). Sitagliptin lowered baseline glycemia but did not affect the primary measures of insulin secretion. However, a significant interaction between sitagliptin and Ex-9 suggested more GLP-1r activation with DPP4i treatment in diabetic subjects.