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

Rapid degradation of glucagon-like peptide-1 (GLP-1) by dipeptidyl peptidase-4 (DPP-4) suggests that endogenous GLP-1 may act locally before being degraded. Signalling 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 ~5-fold 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 ~2-fold higher, and non-suppressible 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, insulin and glucagon secretion, suggesting that intact vagal innervation may be important for GLP-1's actions.