GLUCAGON-LIKE PEPTIDE-1 RETARDS GASTRIC-EMPTYING AND SMALL-BOWEL TRANSIT IN THE RAT - EFFECT MEDIATED THROUGH CENTRAL OR ENTERIC NERVOUS MECHANISMS

This study investigated effects of glucagon-like peptide-1 (7-36)amide (GLP-1) on gastric emptying, small intestinal transit, and contractil ity of smooth muscle strips in rats. GLP-1 at doses of 10 and 20 pmol/ kg/min administered intravenously dose-dependently retarded transit of the small intestine (P < 0.001), while only the higher dose of 20 pmo l/kg/min retarded gastric emptying (P < 0.01). GLP-1 at concentrations up to 10(-4) M did not affect the basal tone or contractility of the gastrointestinal muscle strips that were stimulated with electric fiel d stimulation or acetylcholine. Our results demonstrate that small int estinal transit seems more sensitive than gastric emptying to inhibiti on by GLP-1 at physiologic levels in plasma. Furthermore, this inhibit ion appears to be mediated through central mechanisms rather than thro ugh peripheral actions. Thus, GLP-1 is suggested to inhibit gastric em ptying and small intestinal transit through an indirect effect via cen tral or enteric nervous mechanisms.