Effect of intracerebroventricular infusion of neurotensin in glucose-dependent insulinotropic peptide secretion in dogs

Abstract

GIP is a major physiological component of the enteroinsular axis. Several researchers have pointed to a neural regulation of GIP secretion. We have previously studied the effect of intracerebroventricular (icv) infusion of insulin, NPY and bombesin in the regulation of GIP secretion. The aim of the present study is to evaluate a possible role of neurotensin in neural regulation of GIP secretion. Thirty-two adult dogs were used in this study. In a dose–response study (experiment 1) we used 3 different doses of neurotensin (25, 50 and 100μg) in a bolus icv infusion. In experiment 2 the animals received a bolus icv infusion of 50μg neurotensin and an equivalent amount of artificial cerebrospinal fluid (aCSF) at 1-week interval. In experiment 3 the animals received a continuous icv infusion of neurotensin at a constant rate of 1μg/kg/h and aCSF over a 3-h period, at 1-week interval. In experiment 4 the experiment of group 3 was repeated with a simultaneous intraduodenal infusion of a glucose load through the Mann-Bollman fistula. Plasma levels of glucose, insulin and GIP were assayed. Results: Bolus and continuous icv infusion of neurotensin produced a significant increase in glucose, GIP and insulin levels. In the 4th experiment icv infusion of neurotensin produced a more prominent increase of glucose and insulin levels compare to infusion of aCSF. GIP levels were lower after infusion of neurotensin compared to aCSF. Conclusions: Our data suggest a differential effect of neurotensin on GIP secretion, dependent on the energy load.