The approach for pathogenic mechanism of Type 1 diabetes using transgenic mice expressing TNFalpha selectively in pancreatic beta cells
Project/Area Number |
26350897
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Applied health science
|
Research Institution | Oita University |
Principal Investigator |
Kakuma Tetsuya 大分大学, 保健管理センター, 准教授 (80343359)
|
Co-Investigator(Kenkyū-buntansha) |
正木 孝幸 大分大学, 医学部, 講師 (00423715)
後藤 孔郎 大分大学, 医学部, 助教 (10457624)
柴田 洋孝 大分大学, 医学部, 教授 (20245484)
|
Project Period (FY) |
2014-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
|
Keywords | 膵β細胞特異的TNFα過剰発現マウス / 糖尿病抵抗性 / 肥満抵抗性 / 脂肪肝抵抗性 / 機能的グルカゴン低下 / 糖代謝 / インスリン / グルカゴン / 高脂肪食負荷 / 高ショ糖負荷 / 加齢負荷 / ソマトスタチン / TNFα / AVP |
Outline of Final Research Achievements |
Transgenic mice expressing TNFα selectively in pancreatic βcells developed a severe insulitis, however, apparently resulting in positive glucose metabolism with relatively favorable insulin secretion against over-nutrition. Blood TNFα levels had no induction in transgenic mice because the line with low copy number of TNFα transgene was used in this study. Even though insulin-producing cells were destroyed morphologically and functionally, the effect of insulin was relatively dominant because of the concomitant severe impairments in glucagon and somatostatin by paracrined TNFα. This may provide an explanation for diabetes resistance in TNFα transgenic mice. The experiments of over-nutrition such as high-fat diet and high-sucrose one showed that these mice were also characterized by obesity resistance and fatty liver resistance. TNFα transgenic mice in the present study are considered of value for the model of fatty liver resistance against over-nutrition.
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Report
(4 results)
Research Products
(3 results)
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[Journal Article] Fulminant Type 1 Diabetes Mellitus with Anti-programmed Cell Death-1 Therapy2016
Author(s)
Okamoto M, Okamoto M, Gotoh K, Masaki T, Ozeki Y, Ando H, Anai M, Sato A, Yoshida Y, Ueda S, Kakuma T, Shibata H
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Journal Title
J Diabetes Investig
Volume: 7
Issue: 6
Pages: 915-918
DOI
Related Report
Peer Reviewed
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[Journal Article] Pore alterations of the endothelial lining of rat fenestrated intestinal capillaries exposed to acute stress2016
Author(s)
Aosa T, Chiba S, Kitamura H, Ina K, Tatsukawa S, Moriwaki C, Wei H, Gotoh K, Masaki T, Kakuma T, Shibata H, Fujikura Y
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Journal Title
Histol Histopathol
Volume: 31
Pages: 807-817
Related Report
Peer Reviewed
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