2012 Fiscal Year Final Research Report

Establishment of the alpha cell analytical methods and the clarification of the mechanism for alpha cell dysfunction

Research Project

Project/Area Number	23659169
Research Category	Grant-in-Aid for Challenging Exploratory Research
Allocation Type	Multi-year Fund
Research Field	Pathological medical chemistry
Research Institution	Gunma University
Principal Investigator	KITAMURA Tadahiro 群馬大学, 生体調節研究所, 教授 (20447262)
Project Period (FY)	2011 – 2012
Keywords	糖尿病 / FoxO1 / ATF3 / α細胞
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.

(4 results)