Analysis of glucose-stimulated insulin secretion in transgenic mice overexpressing PACAP in pancreas and PACAP deficient mice

• Published in: Japanese Journal of Pharmacology 2001, Vol.85 (suppl.1), p.189-189
• Main Authors: Shuhei Tomimoto, Hitoshi Hashimoto, Kyohei Yamamoto, Norihito Shintani, Tatsuya Ojika, Akemichi Baba
• Format: Article
• Language: Japanese
• ISSN: 0021-5198

Pituitary adenylate cyclase-activating polypeptide (PACAP) is expressed not only in the brain but also in peripheral tissues such as the testis, adrenal gland, and pancreas. In the pancreas, PACAP as low as 10^13 M stimulates insulin secretion from rat isolated islets in a glucose-dependent manner, indicating that PACAP has the most potent insulinotropic effect in the factors ever investigated. We have previously generated the transgenic mice overexpressing PACAP precursor in the pancreas specifically under the control of the human insulin promoter. Very recently, we have also generated the PACAP deficient mice. In this study, we analyzed the glucose-stimulated insulin secretion of these mutant mice to determine the function of PACAP in the pancreas in vivo. Both PACAP transgenic and deficient mice showed normal plasma glucose level compared to their littermate wild-type mice. However, transgenic mice showed slightly higher plasma insulin level in response to intraperitoneal glucose injection compared to littermate non-transgenic mice. In contrast, PACAP deficient mice showed slightly lower plasma insulin level in response to intraperitoneal glucose injection. These results indicate that PACAP is required to insulin secretory responseiveness to glucose.