| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Research Abstract |
We tried to elucidate the significance of ATF3 and FoxO1 in the development of type 2 diabetes. First, there was no difference in the expression levels and subcellular localization of ATF3 and FoxO1 in the alpha cells of type 2 diabetic model mice. We next generated the pancreas-specific ATF3 knockout mice and analyzed metabolic parameters and the pancreas morphology. However, we couldn't find any significant change in blood glucose levels, glucose tolerance, plasma glucagon and plasma insulin levels in these mice. Furthermore, alpha cell and beta cell mass were comparable between knockout mice and control mice. By contrast, alpha cell specific FoxO1 knockin mice showed significantly increased blood glucose levels and impaired glucose tolerance compared to the control mice, which was accompanied with increased plasma glucagon levels. Thus, FoxO1 in alpha cell is important for the regulation of glucosemetabolism, but the contribution of ATF3 seems to be less important.
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