The insulin response to gastric glucose is reduced in PAC1 and GRP receptor gene deleted mice

Background and aims: Islet function is regulated by islet autonomic nerves. These nerves harbour not only the classical neurotransmitters, acetyl choline and noradrenaline, but also neuropeptides. This study examined whether the neuropeptides, pituitary adenylate cyclase activating polypeptide (PACAP) and gastrin releasing polypeptide (GRP) contribute to the regulation of insulin secretion in model experiments by using receptor gene deleted mice. Methods: Anaesthetized mice with genetic deletion of one of the PACAP receptors (PAC1 receptors) or one of the GRP receptors (GRP receptor) or their wildtype counterparts were given glucose through a gastric gavage (1150 mg) or intravenously (0.25, 0.50 or 1 g/kg). Blood samples were taken regularly during the following 120 min (after gastric glucose) or at 1 min (after intravenous glucose) for analysis of glucose and insulin. Results: The insulin response to gastric glucose was suppressed by 66% in PAC1 receptor gene deleted mice in association with impaired glucose elimination, whereas the insulin response to intravenous glucose was impaired by 36% only. The insulin response to glucose was suppressed in GRP receptor gene deleted mice by 24% together with impaired glucose elimination, whereas the insulin response to intravenous glucose was not significantly suppressed. Conclusions: The insulin responses to gastric versus intravenous glucose in receptor gene deleted mice show that PACAP, and to a lesser extent GRP, contributes to the insulin response to gastric administration of glucose. (c) 2005 Elsevier B.V. All rights reserved.