Role of GCN2 in the onset of type 2 diabetes induced by high fat diet.

2015 Fiscal Year Final Research Report

• Project/Area Number: 26750040
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Eating habits
• Research Institution: Kobe University
• Principal Investigator: Maki Kimura-Koyanagi (小柳真希) 神戸大学, 医学(系)研究科(研究院), 研究員 (40623690)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: アミノ酸 / mTORC1

Outline of Final Research Achievements

Single-nucleotide polymorphism (SNP) analysis of Japanese diabetes patients has revealed a significant correlation between a general control nonderepressible 2 (GCN2) SNP and type 2 diabetes mellitus (T2DM).
GCN2-/- mice fed a NCD did not exhibit any changes in glucose tolerance or pancreatic β-cell mass. However, GCN2-/- mice fed an HFD exhibited significant aggravation in glucose tolerance and reduction in pancreatic β-cell mass. Islets isolated from GCN2-/- mice showed significant increase in mTORC1 activity and decrease in insulin signaling. We compared amino acid levels in islets from wild-type mice fed a NCD with those fed an HFD, and found that a lot of amino acids are decreased in islets from mice fed an HFD. Moreover, we found decreases in charging level of tRNAs in islets from mice fed an HFD.From our data, we consider that activated GCN2 contributes to the maintenance of pancreatic β-cell mass.

Free Research Field

2型糖尿病