Physiological and pathophysiological roles of KCNQ1 as a susceptibility gene for type 2 diabetes mellitus

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09377
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: The University of Tokyo
• Principal Investigator: Takamoto Iseki 東京大学, 医学部附属病院, 助教 (60431871)
• Research Collaborator: KUBOTA Naoto ; NAKAYA Keizo ; KUMAGAI Katsuyoshi ; KUBOTA Tetsuya ; INOUE Mariko ; SAKURAI Yoshitaka ; IWAMOTO Masahiko ; YOSHIDA Masashi ; HARA Kazuo ; UEKI Kohjiro ; KADOWAKI Takashi
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 2型糖尿病 / 疾患感受性遺伝子 / KCNQ1

Outline of Final Research Achievements

Common genetic variations of KCNQ1 are associated with type 2 diabetes. In this study, we investigated the physiological and pathophysiological roles of KCNQ1 in glucose homeostasis with several genetically engineered mice. We have identified novel genetically engineered mice with loss-of-function KCNQ1 caused by a single-nucleotide mutation, which showed no obvious glucose intolerance. By contrast, mice with gain -of-function KCNQ1 in in the pancreatic beta cells were associated with a reduction of insulin secretion, leading to impaired glucose tolerance. Thus, our findings suggest that functional up-regulation and/or over-expression of KCNQ1 in the pancreatic beta cells play a crucial role in glucose metabolism in vivo.

Free Research Field

糖尿病