The approach for pathogenic mechanism of Type 1 diabetes using transgenic mice expressing TNFalpha selectively in pancreatic beta cells

2016 Fiscal Year Final Research Report

• 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)
• Project Period (FY): 2014-04-01 – 2017-03-31
• 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

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.

Free Research Field

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