@article{oai:kanazawa-u.repo.nii.ac.jp:00027367,
 author = {大島, 浩子 and 大島, 正伸 and Oshima, Hiroko and Taketo, Makoto Mark and Oshima, Masanobu},
 issue = {39},
 journal = {Journal of Biological Chemistry},
 month = {Sep},
 note = {Type 2 diabetes mellitus is characterized by insulin resistance of peripheral tissues and dysfunction of pancreatic β-cells. Furthermore, the number of pancreatic β-cells decreases as a secondary effect of advanced type 2 diabetes, although the molecular mechanism has not been elucidated. Recently, it has been shown that hyperglycemic conditions induce the expression of cyclooxygenase-2 in pancreatic islets and increase the downstream product prostaglandin E2 (PGE2). To investigate whether high glucose-induced PGE2 has an adverse effect on pancreatic β-cells, we generated transgenic mice (RIP-C2mE) that express cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in their β-cells using the rat insulin-2 gene promoter (RIP). The homozygous RIP-C2mE (Tg/Tg) mice showed severe hyperglycemia from six weeks of age. Although the heterozygous RIP-C2mE (Tg/-) mice showed normal blood glucose levels throughout their lifetime, this level increased significantly compared with that of wild-type mice when glucose was loaded. The relative number of β-cells to the total islet cell number was reduced to 54 and 14% in the RIP-C2mE (Tg/-) and (Tg/Tg) mice, respectively, whereas that in the wild-type mice was 84%. Importantly, the proliferation rate in the islets of the RIP-C2mE (Tg/Tg) mice at four weeks of age decreased significantly in comparison to that in the wild-type mice. Because β-cells replicate not only during the postnatal period but also in the adult pancreas at a basal level, it is possible that increased PGE2 signaling thus contributes to the reduction of the pancreatic β-cell mass through inhibition of proliferation, thereby aggravating diabetes further. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc., 金沢大学がん研究所附属がん幹細胞研究センター},
 pages = {29330--29336},
 title = {Destruction of pancreatic β-cells by transgenic induction of prostaglandin e2 in the islets},
 volume = {281},
 year = {2006}
}