GLUCAGON-LIKE PEPTIDE-1 INHIBITION OF GASTRIC-EMPTYING OUTWEIGHS ITS INSULINOTROPIC EFFECTS IN HEALTHY HUMANS

Glucagon-like peptide 1 (GLP-1) has been shown to inhibit gastric empt ying of liquid meals in type 2 diabetic patients. It was the aim of th e present study to compare the action of physiological and pharmacolog ical doses of intravenous GLP-1-(7-36) amide and GLP-1-(7-37) on gastr ic emptying in normal volunteers. Nine healthy subjects participated ( 26 +/- 3 yr; body mass index 22.9 +/- 1.6 kg/m(2); hemoglobin A(1C) 5. 0 +/- 0.2%) in five experiments on separate occasions after an overnig ht fast. A nasogastric tube was positioned for the determination of ga stric volume by use of a dye-dilution technique (phenol red). GLP-1-(7 -36) amide (0.4, 0.8, or 1.2 pmol.kg(-1).min(-1)), GLP-1-(7-37) (1.2 p mol.kg(-1).min(-1)), or placebo was infused intravenously from -30 to 240 min. A liquid meal(50 g sucrose, 8% amino acids, 440 ml, 327 kcal) was administered at 0 min. Glucose, insulin, and C-peptide were measu red over 240 min. Gastric emptying was dose dependently slowed by GLP- 1-(7-36) amide (P < 0.0001). Effects of GLP-1-(7-37) at 1.2 pmol.kg(-1 ).min(-1) were virtually identical. GLP-1 dose dependently stimulated fasting insulin secretion (-30 to 0 min) and slightly reduced glucose concentrations. After the meal (0-240 min), integrated incremental glu cose (P < 0.0001) and insulin responses (P = 0.01) were reduced (dose dependently) rather than enhanced. In conclusion, 1) GLP-1-(7-36) amid e or -(7-37) inhibits gastric emptying also in normal subjects, 2) phy siological doses (0.4 pmol.kg(-1).min(-1)) still have a significant ef fect, 3) despite the known insulinotropic actions of GLP-1-(7-36) amid e and -(7-37), the net effect of administering GLP-1 with a meal is no change or a reduction in meal-related insulin responses. These findin gs suggest a primarily inhibitory function for GLP-1 (ileal brake mech anisms).