Effects of transgenic overexpression of pancreatic PACAP on obesity-associated diabetes

• Published in: Journal of Pharmacological Sciences 2004, Vol.94 (suppl.2), p.207-207
• Main Authors: Yuki Kawabata, Shuhei Tomimoto, Hitoshi Hashimoto, Ken-ichi Hamagami, Norihito Shintani, Akemichi Baba
• Format: Article
• Language: Japanese
• ISSN: 1347-8613

Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates glucose-dependent insulin release. To examine the role of PACAP in obesity-diabetes, we crossed our recently developed transgenic mice overexpressing PACAP in pancreatic β-cells (Tg/+), with lethal yellow agouti (KKAy) mice (Ay/+), a genetic model for obesity-associated diabetes, and analyzed F1 mice. The hyperinsulimenia observed in Ay/+ mice was markedly attenuated in Tg/+ mice with Ay allele (Tg/+:Ay/+), and an enhanced first-phase insulin response to a glucose load in Ay/+ mice was significantly attenuated in Tg/+:Ay/+ mice. We further examined the effect of PACAP overexpression in leptin receptor-deficient (db/db) mice. db/db mice carrying the PACAP transgene (Tg/+:db/db) showed no difference in metabolic characteristics compared with db/db mice, although both db/db and Tg/+:db/db showed a marked increase in body weight, plasma insulin and glucose levels. The present results suggest that PACAP overexpressed in pancreatic β-cells affects diabetic phenotype, likely depending on the genetic factors of the models studied.