GLP-1 antagonism with exendin (9-39) fails to increase spontaneous meal size in rats.
Intravenous and intraperitoneal (IP) administration of glucagon like peptide-1 (7-36)-amide (GLP-1) inhibits eating, but the physiological relevance of this satiating effect is not yet clear. We addressed this issue by testing the effects of the GLP-1 receptor antagonist exendin 9-39 (Ex (9-39)) on spontaneous eating and on the satiating effect of exogenous GLP-1. Adult, male Sprague-Dawley rats were equipped with chronic IP catheters and received intrameal infusions (0.2 ml/min, 2.5 min) that were remotely triggered 2-3 min after the onset of the first or the second spontaneous nocturnal meal. Infusions of 10, but not 5 or 2.5 nmol/kg body weight (BW) GLP-1 significantly reduced the size of the first spontaneous nocturnal meal compared to vehicle. The first intermeal interval, subsequent meal sizes and cumulative food intake were unchanged by 10 nmol/kg GLP-1. Infusions of 10 or 30 nmol/kg BW Ex (9-39) during the second spontaneous nocturnal meal did not affect the size of that meal and decreased rather than increased meal duration. Co-infusion of 30 nmol/kg BW Ex (9-39) prevented the satiating effect of 10 nmol/kg BW GLP-1 during the first spontaneous nocturnal meal, but again did not increase meal size by itself. That a dose of Ex (9-39) that is sufficient to block the satiating effect of exogenous GLP-1 failed to increase meal size when administered alone under comparable conditions suggests that endogenous intestinal GLP-1 is not required for the control of spontaneous meal size in rats under our conditions. The situations in which GLP-1 is of physiological relevance for satiation require further research.
Rüttimann
Elisabeth B
EB
Physiology and Behaviour Laboratory, Institute of Food, Nutrition and Health, ETH Zurich, Schorenstrasse 16, 8603 Schwerzenbach, Switzerland.
Arnold
Myrtha
M
Geary
Nori
N
Langhans
Wolfgang
W
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage* / Q000037:antagonists & inhibitors*; D007263:Infusions, Parenteral; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012528:Satiety Response / Q000187:drug effects*
D010446:Peptide Fragments; C083773:exendin (9-39); D052216:Glucagon-Like Peptide 1