Hepatic glucose and lipid homeostasis in type 2 diabetes with obesity

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04847
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: The University of Tokyo
• Principal Investigator: Kubota Naoto 東京大学, 医学部附属病院, 准教授 (50396719)
• Co-Investigator(Renkei-kenkyūsha): Kadowaki Takashi 東京大学, 医学部附属病院, 教授 (30185889)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: インスリン受容体基質

Outline of Final Research Achievements

By investigating differential insulin signaling in the periportal (PP) zone, the site of gluconeogenesis, and perivenous (PV) zone, the site of lipogenesis, of the liver, we found that insulin signaling mediated by Irs1 and Irs2 was impaired in the PP zone, but rather enhanced in the PV zone, caused by the downregulation by hyperinsulinemia of Irs2, which is similarly expressed in both the PP and PV zones, coupled with intact expression of Irs1, which is predominantly expressed in the PV zone and is not affected by hyperinsulinemia. These data suggest that “selective insulin resistance” is induced by the differential distribution and alterations of hepatic Irs1 and Irs2 expressions in type 2 diabetes and obesity.

Free Research Field

糖尿病代謝