The Effect of Exogenous GLP-1 on Food Intake is Lost in Male Truncally Vagotomized Subjects with Pyloroplasty

TY - JOUR

T1 - The Effect of Exogenous GLP-1 on Food Intake is Lost in Male Truncally Vagotomized Subjects with Pyloroplasty

AU - Plamboeck, Astrid

AU - Veedfald, Simon

AU - Deacon, Carolyn F

AU - Hartmann, Bolette

AU - Wettergren, Andre

AU - Svendsen, Lars Bo

AU - Meisner, Søren

AU - Hovendahl, Claus

AU - Vilsboll, Tina

AU - Knop, Filip K

AU - Holst, Jens Juul

PY - 2013/6/16

Y1 - 2013/6/16

N2 - 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.

AB - 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.

U2 - 10.1152/ajpgi.00035.2013

DO - 10.1152/ajpgi.00035.2013

M3 - Journal article

C2 - 23599045

SN - 0193-1857

VL - 304

SP - G1117-G1127

JO - American Journal of Physiology: Gastrointestinal and Liver Physiology

JF - American Journal of Physiology: Gastrointestinal and Liver Physiology

ER -