SUBCUTANEOUS INJECTION OF THE INCRETIN HORMONE GLUCAGON-LIKE PEPTIDE-1 ABOLISHES POSTPRANDIAL GLYCEMIA IN NIDDM

OBJECTIVE- To investigate the effect of subcutaneously injected glucag on-like peptide 1 (GLP-1) (7-36)amide on postprandial plasma glucose, insulin, and C-peptide levels in patients with non-insulin-dependent d iabetes mellitus (NIDDM) and a secondary failure to sulfonylureas. RES EARCH DESIGN AND METHODS- GLP-1 (25 nmol) was injected subcutaneously into either the abdominal wall or the gluteal region at a standardized depth and speed. The injection device was guided by the ultrasound de termination of the depth of the fat layer. The peptide was given 5 min before a standard meal. Plasma concentrations of glucose, C-peptide, insulin, glucagon, and GLP-1 were followed during 240 min after the in jection. RESULTS- In control experiments, a significant hyperglycemia was attained after the meal. GLP-1 given into the abdominal wall not o nly virtually abolished the postprandial blood glucose rise but signif icantly decreased glucose concentrations, with a nadir at similar to 2 5 min after the injection. A rapid rise of C-peptide and insulin level s was observed 10-15 min after the injection of GLP-1. The stimulatory effect of GLP-1 was transient, and, at 45 min after the meal, both in sulin and C-peptide levels were almost identical in GLP-1 and control experiments. Significantly lower glucagon concentrations were observed 35-65 min after the peptide injection. GLP-1 concentration in plasma increased from 10 pM to a peak concentration (C-max) of 70 pM at T-max 30 min after injection. Then GLP-1 levels rapidly decreased to 25 pM at 95 min and returned to basal at 215 min. The gluteal injection of G LP-1 had similar effects compared with the abdominal administration on plasma levels of glucose, insulin, C-peptide, and glucagon. CONCLUSIO NS- GLP-1 is promptly absorbed from the subcutaneous tissue. It exerts a significant blood glucose lowering effect when administered before meals in overweight patients with NIDDM.