2009 Fiscal Year Final Research Report

Investigation of the mechanism by which TCF7L2 gene develops Type 2 diabetes

Research Project

Project/Area Number	20790639
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Single-year Grants
Research Field	Metabolomics
Research Institution	The University of Tokyo
Principal Investigator	HORIKOSHI Momoko The University of Tokyo, 医学部附属病院, 助教 (70422300)
Research Collaborator	TAKAMOTO Iseki 東京大学, 医学部付属病院
Project Period (FY)	2008 – 2009
Keywords	2型糖尿病 / 遺伝子 / インスリン分泌
Research Abstract	TCF7L2 gene is widely accepted as a type 2 diabetes (T2D)-associated gene, the mechanism through which, however, is not well known. Thus we investigated its correlation with glucose metabolism by generating a TCF7L2 knock-down mouse with decreased function of TCF7L2 in the pancreatic beta cell. Glucose level of the TCF7L2 knock-down mouse during oral glucose tolerance test (OGTT) was significantly higher compared to the wild type mouse, and its insulin level was lower. Likewise, in human subjects who were homozygous for the T2D risk allele of TCF7L2rs7903146, the glucose levels at 90 min were significantly higher and the insulin levels at 120 min were significantly lower compared to the subjects with no risk allele during 75gOGTT. In conclusion, we demonstrated that the decrease of TCF7L2 function in the pancreatic beta cell will cause glucose intolerance through decreased insulin secretion.

(4 results)