GASTRIC-EMPTYING GLUCOSE RESPONSES, AND INSULIN-SECRETION AFTER A LIQUID TEST MEAL - EFFECTS OF EXOGENOUS GLUCAGON-LIKE PEPTIDE-1 (GLP-1)-(7-36) AMIDE IN TYPE-2 (NONINSULIN-DEPENDENT) DIABETIC-PATIENTS

The aim of the study was to investigate whether inhibition of gastric emptying of meals plays a role in the mechanism of the blood glucose-l owering action of glucagon-like peptide-1-(7-36) amide [GLP-1-(7-36) a mide] in type 2 diabetes. Eight poorly controlled type 2 diabetic pati ents (age, 58 +/- 6 yr; body mass index, 30.0 +/- 5.2 kg/m(2); hemoglo bin A(1C) , 10.5 +/- 1.2%) were studied in the fasting state (plasma g lucose, 11.1 +/- 1.1 mmol/L). A liquid meal of 400 mL containing 8% am ino acids and 50 g sucrose (327 Kcal) was administered at time zero by a nasogastric tube. Gastric volume was determined by a dye dilution t echnique using phenol red. In randomized order, GLP-1-(7-36) amide (1. 2 pmol/kg . min; Saxon Biochemicals) or placebo (0.9% NaCl with 1% hum an serum albumin) was infused between -30 and 240 min. In the control experiment, gastric emptying was completed within 120 min, and plasma glucose, insulin, C-peptide, GLP-1-(7-36) amide, and glucagon concentr ations transiently increased. With exogenous GLP-1-(7-36) amide (plasm a level, similar to 70 pmol/L), gastric volume remained constant over the period it was measured (120 min; P < 0.0001 vs. placebo), and plas ma glucose fell to normal fasting values (5.4 +/- 0.7 mmol/L) within 3 -4 h, whereas insulin was stimulated in most, but not all, patients, a nd glucagon remained at the basal level or was slightly suppressed. In conclusion, GLP-1-(7-36) amide inhibits gastric emptying in type 2 di abetic patients. Together with the stimulation of insulin and the inhi bition of glucagon secretion, this effect probably contributes to the blood glucose-lowering action of GLP-1-(7-36) amide in type a-diabetic patients when studied after meal ingestion. At the degree observed, i nhibition of gastric emptying, however, must be overcome by tachyphyla xis, reduction in dose, or pharmacological interventions so as not to interfere with the therapeutic use of GLP-1-(7-36) amide in type 2 dia betic patients.