Exploring mechanisms of distorted glucagon secretion in type 1 diabetes using a novel alpha-cell model of insulin deficiency

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461367
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Osaka Medical College
• Principal Investigator: Mishiba Yuko (村瀬裕子) 大阪医科大学, 医学部, 助教 (80377415)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: グルカゴン / 膵α細胞 / 1型糖尿病 / メタボローム解析

Outline of Final Research Achievements

To investigate the metabolic traits that underlie the distortion of glucagon secretion in insulin deficiency, we generated an αTC1-6 cell line with stable knockdown of the insulin receptor (IRKD), i.e., an in vitro α-cell model for type 1 diabetes (T1D), which exhibits an abnormal glucagon response to glucose. A comprehensive metabolomic analysis of the IRKD αTC1-6 cells (IRKD cells) revealed some candidate metabolites whose levels differed markedly compared to those in control αTC1-6 cells. Of these candidates, taurine was remarkably increased in the IRKD cells and was identified as a stimulator of glucagon in αTC1-6 cells. These results indicate that the metabolic alterations induced by IRKD in α-cells, especially the increase of taurine, may lead to the distorted glucagon response in IRKD cells, suggesting the importance of taurine in the paradoxical glucagon response in T1D.

Free Research Field

糖尿病内分泌代謝学