Novel regulatory mechanism of insulin activity through IRS monoubiquitination

2014 Fiscal Year Final Research Report

• Project/Area Number: 24790928
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Hiroshima University
• Principal Investigator: FUKUSHIMA Toshiaki 広島大学, 医歯薬保健学研究院, 助教 (70543552)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: インスリン / インスリン様成長因子 / インスリン受容体基質 / 糖尿病 / ユビキチン

Outline of Final Research Achievements

Insulin is a hormone that regulates blood glucose levels. Insulin-like growth factor (IGF) is another hormone similar in molecular structure to insulin, and IGF promotes cell proliferation and body growth. We previously found that insulin receptor substrate (IRS), a protein that mediates insulin/IGF intracellular signaling, is functionally changed by its modification called as "monoubiquitination", and it leads to the enhancement of insulin/IGF signaling and induction of their bioactivities. In this study, we elucidated the detailed molecular mechanisms underlying the enhancement of insulin/IGF signaling by IRS monoubiquitination. Furthermore, we found that, when the amounts of nutrition given to hepatocytes are changed, hepatic insulin sensitivity also changed through this novel mechanism. This finding is thought to be important for understanding pathogenic mechanism of diabetes.

Free Research Field

インスリンやインスリン様成長因子の細胞内シグナル伝達機構の研究