2017 Fiscal Year Final Research Report
Elucidation the roles of senescence-like phenotype in pancreatic beta-cells in diabetic mutant cryptochrome1 transgenic mice
| Project/Area Number |
15K08417
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Yamagata University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
中島 修 山形大学, 医学部, 教授 (80312841)
安井 明 東北大学, 加齢医学研究所, 加齢研フェロー (60191110)
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| Co-Investigator(Renkei-kenkyūsha) |
SATOH KENNICHI 東北医科薬科大学, 医学部, 教授 (10282055)
HAYASAKA KIYOSHI 山形大学, 医学部, 名誉教授 (20142961)
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| Research Collaborator |
KANNO SHINICHIROU 東北大学, 加齢医学研究所, 講師
IGARASHI MASAHIKO 山形市立病院済生館, 地域糖尿病センター, センター長
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | 糖尿病 / 細胞老化関連分泌形質(SASP) / 膵島構造リモデリング / 膵上皮内腫瘍性病変(PanIN) / 膵癌前駆病変 / KPNA2（インポーティンα1） / 膵β細胞-膵管細胞分化転換 / 亜鉛結合変異mCRY1(C414A-CRY1) |
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| Outline of Final Research Achievements |
Our research group (the study network of Cryptochrome in Tohoku Area [principal investigator: Sstoshi Okano]) have showed that, from the research over 10 years, the zinc-binding site-mutant (C414A) mCRY1 Tg mice display diabetes characterized by β-cell dysfunction due to senescence-like features of pancreatic β-cells.
To elucidate the pathogenesis, we conducted analyses of the pancreas of the aged Tg mice. We newly found that the extent of fibrosis of the islet was higher in Tg mice compared with wild-type controls. Unusual duct-like structures producing mucin developed inside islets in the Tg mice with age. Outside islets, PanIN-like ductal structures, which are surrounded by pancreatic duct glands (PDG), were prominently emerged in aged Tg mice. Our results strongly suggest that, SASP-like microenvironment in the islets of the Tg mice play stimulatory roles in the transdifferentiation of pancreatic β-cells to ductal cells and in the development of ductal dysplasia in the Tg mice.
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| Free Research Field |
膵β細胞の生物学, 膵癌前駆病変, 時間生物学
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