MECHANISMS OF THE ANTIDIABETIC ACTION OF SUBCUTANEOUS GLUCAGON-LIKE PEPTIDE-1(7-36)AMIDE IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS

Twelve patients with non-insulin dependent diabetes mellitus (NIDDM) u nder-secondary failure to sulfonylureas were studied to evaluate the e ffects of subcutaneous glucagon-like peptide-1(7-36)amide (GLP-1) on ( a) the gastric emptying pattern of a solid meal (250 kcal: and (b) the glycemic and endocrine responses to this solid meal and an oral gluco se tolerance test (OGTT, 300 kcal). 0.5 nmol/kg of GLP-1 or placebo we re subcutaneously injected 20 min alter meal ingestion. GLP-1 modified the pattern of gastric emptying by prolonging the time to reach maxim al emptying velocity (lag period) which was followed by an acceleratio n in the post-lag period. The maximal emptying velocity and the emptyi ng half-time remained unaltered. With both meals, GLP-1 diminished til e postprandial glucose peak, and reduced the glycemic response during the first two postprandial hours by 54.5% (solid meal) and 32.7% (OGTT ) (P<0.05). GLP-1 markedly stimulated insulin secretion with an effect lasting for 105 min (solid meal) or 150 min (OGTT). The postprandial increase of plasma glucagon was abolished by GLP-1. GLP-1 diminished t he postprandial release of pancreatic polypeptide. The initial and tra nsient delay of gastric emptying, the enhancement of postprandial insu lin release, and the inhibition of postprandial glucagon release were interdependent determinants (P<0.002) of the postprandial glucose resp onse after subcutaneous GLP-1. An inhibition of efferent vagal activit y may contribute to the inhibitory effect of GLP-1 on gastric emptying .