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 contractility 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 pmol/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 field stimulation or acetylcholine. Our results demonstrate that small intestinal transit seems more sensitive than gastric emptying to inhibition by GLP-1 at physiologic levels in plasma. Furthermore, this inhibition appears to be mediated through central mechanisms rather than through peripheral actions. Thus, GLP-1 is suggested to inhibit gastric emptying and small intestinal transit through an indirect effect via central or enteric nervous mechanisms.
Tolessa
T
T
Department of Medicine, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
Gutniak
M
M
Holst
J J
JJ
Efendic
S
S
Hellström
P M
PM
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002490:Central Nervous System / Q000502:physiology; D004558:Electric Stimulation; D017615:Enteric Nervous System / Q000502:physiology; D005746:Gastric Emptying / Q000187:drug effects*; D005772:Gastrointestinal Transit / Q000187:drug effects*; D005934:Glucagon / Q000097:blood / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010446:Peptide Fragments / Q000097:blood / Q000494:pharmacology*; D011498:Protein Precursors / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D010446:Peptide Fragments; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000109:Acetylcholine