Analysis of rat insulin II promoter-ghrelin transgenic mice and rat glucagon promoter-ghrelin transgenic mice

Hiroshi Iwakura, Kiminori Hosoda, Choel Son, Junji Fujikura, Tsutomu Tomita, Michio Noguchi, Hiroyuki Ariyasu, Kazuhiko Takaya, Hiroaki Masuzaki, Yoshihiro Ogawa, Tatsuya Hayashi, Gen Inoue, Takashi Akamizu, Hiroshi Hosoda, Masayasu Kojima, Hiroshi Itoh, Shinya Toyokuni, Kenji Kangawa, Kazuwa Nakao

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Abstract

We developed and analyzed two types of transgenic mice: rat insulin II promoter-ghrelin transgenic (RIP-G Tg) and rat glucagon promoter-ghrelin transgenic mice (RGP-G Tg). The pancreatic tissue ghrelin concentration measured by C-terminal radioimmunoassay (RIA) and plasma desacyl ghrelin concentration of RIP-G Tg were about 1000 and 3.4 times higher than those of nontransgenic littermates, respectively. The pancreatic tissue n-octanoylated ghrelin concentration measured by N-terminal RIA and plasma n-octanoylated ghrelin concentration of RIP-G Tg were not distinguishable from those of nontransgenic littermates. RIP-G Tg showed suppression of glucose-stimulated insulin secretion. Arginine-stimulated insulin secretion, pancreatic insulin mRNA and peptide levels, β cell mass, islet architecture, and GLUT2 and PDX-1 immunoreactivity in RIP-G Tg pancreas were not significantly different from those of nontransgenic littermates. Islet batch incubation study did not show suppression of insulin secretion of RIP-G Tg in vitro. The insulin tolerance test showed lower tendency of blood glucose levels in RIP-G Tg. Taking lower tendency of triglyceride level of RIP-G Tg into consideration, these results may indicate that the suppression of insulin secretion is likely due to the effect of desacyl ghrelin on insulin sensitivity. RGP-G Tg, in which the pancreatic tissue ghrelin concentration measured by C-RIA was about 50 times higher than that of nontransgenic littermates, showed no significant changes in insulin secretion, glucose metabolism, islet mass, and islet architecture. The present study raises the possibility that desacyl ghrelin may have influence on glucose metabolism.

Original languageEnglish
Pages (from-to)15247-15256
Number of pages10
JournalJournal of Biological Chemistry
Volume280
Issue number15
DOIs
Publication statusPublished - 2005 Apr 15

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Iwakura, H., Hosoda, K., Son, C., Fujikura, J., Tomita, T., Noguchi, M., Ariyasu, H., Takaya, K., Masuzaki, H., Ogawa, Y., Hayashi, T., Inoue, G., Akamizu, T., Hosoda, H., Kojima, M., Itoh, H., Toyokuni, S., Kangawa, K., & Nakao, K. (2005). Analysis of rat insulin II promoter-ghrelin transgenic mice and rat glucagon promoter-ghrelin transgenic mice. Journal of Biological Chemistry, 280(15), 15247-15256. https://doi.org/10.1074/jbc.M411358200