title: The effect of exogenous GLP-1 on food intake is lost in male truncally vagotomized subjects with pyloroplasty.
abstract: Rapid degradation of glucagon-like peptide-1 (GLP-1) by dipeptidyl peptidase-4 suggests that endogenous GLP-1 may act locally before being degraded. Signaling via the vagus nerve was investigated in 20 truncally vagotomized subjects with pyloroplasty and 10 matched healthy controls. Subjects received GLP-1 (7-36 amide) or saline infusions during and after a standardized liquid mixed meal and a subsequent ad libitum meal. Despite no effect on appetite sensations, GLP-1 significantly reduced ad libitum food intake in the control group but had no effect in the vagotomized group. Gastric emptying was accelerated in vagotomized subjects and was decreased by GLP-1 in controls but not in vagotomized subjects. Postprandial glucose levels were reduced by the same percentage by GLP-1 in both groups. Peak postprandial GLP-1 levels were approximately fivefold higher in the vagotomized subjects. Insulin secretion was unaffected by exogenous GLP-1 in vagotomized subjects but was suppressed in controls. GLP-1 significantly reduced glucagon secretion in both groups, but levels were approximately twofold higher and were nonsuppressible in the early phase of the meal in vagotomized subjects. Our results demonstrate that vagotomy with pyloroplasty impairs the effects of exogenous GLP-1 on food intake, gastric emptying, and insulin and glucagon secretion, suggesting that intact vagal innervation may be important for GLP-1's actions.
authors.affiliation: Diabetes Research Division, Department of Internal Medicine, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. astridp@sund.ku.dk
authors.forename: Astrid
authors.initials: A
authors.lastname: Plamboeck
authors.forename: Simon
authors.initials: S
authors.lastname: Veedfald
authors.forename: Carolyn F
authors.initials: CF
authors.lastname: Deacon
authors.forename: Bolette
authors.initials: B
authors.lastname: Hartmann
authors.forename: André
authors.initials: A
authors.lastname: Wettergren
authors.forename: Lars B
authors.initials: LB
authors.lastname: Svendsen
authors.forename: Søren
authors.initials: S
authors.lastname: Meisner
authors.forename: Claus
authors.initials: C
authors.lastname: Hovendal
authors.forename: Tina
authors.initials: T
authors.lastname: Vilsbøll
authors.forename: Filip K
authors.initials: FK
authors.lastname: Knop
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
mesh_terms: D000368:Aged; D004381:Duodenal Ulcer / Q000601:surgery; D004435:Eating / Q000187:drug effects*; D005746:Gastric Emptying / Q000187:drug effects; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D062407:Meals; D011708:Pylorus / Q000294:innervation / Q000601:surgery*; D014628:Vagotomy
chemical_list: D007328:Insulin; D052216:Glucagon-Like Peptide 1; D005934:Glucagon
keywords: DPP-4; GLP-1; degradation; insulin and glucagon secretion; meal test; vagotomy; vagus nerve