NEURAL MODULATION OF GLUCOSE-DEPENDENT INSULINOTROPIC PEPTIDE (GIP) AND INSULIN-SECRETION IN CONSCIOUS DOGS

Glucose-dependent insulinotropic peptide (GIP) is a potent incretin, b ut it remains unclear whether this effect is dependent upon intact vag al pathways. In four conscious dogs, plasma GIP, plasma insulin, and p lasma glucose responses were measured after intraduodenal administrati on of a defined formula diet, after glucose was perfused intraduodenal ly, and after insulinmediated hypoglycemia with and without bilateral cryogenic blockade of the cervical vagus nerves. Vagal blockade did no t alter elevations of plasma GIP after the defined formula diet or aft er glucose. However, with the vagi blocked plasma insulin responses we re suppressed after the enteral diet (-52 +/- 8%) and after intraduode nal glucose (-55 +/- 4%), without changes in plasma glucose. Intraveno us atropine (50 mu g/kg) did not modify the GIP responses to intraduod enal perfusions of the defined formula diet or to glucose, but did sup press plasma insulin responses to baseline values. Insulin hypoglycemi a without or with vagal blockade had no effect on basal concentrations of plasma GIP. These results indicate that vagal muscarinic and nonva gal muscarinic pathways participate in the control of the intestinal p hase of insulin secretion, but the regulation of GIP secretion is inde pendent of vagal or muscarinic neural control mechanisms.