IRS-2 in the CNS regulates food intake and glucose homeostasis

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860702
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: National Institutes of Biomedical Innovation, Health and Nutrition (2015); National Institute of Health and Nutrition (2014)
• Principal Investigator: INOUE MARIKO 国立研究開発法人医薬基盤・健康・栄養研究所, 臨床栄養研究部, 室長 (80511477)
• Research Collaborator: Naoto Kubota 東京大学, 大学院医学系研究科・医学部 病態栄養治療部, 部長 (50396719) ; Tetsuya Kubota 理化学研究所, 統合生命医科学研究センター代謝恒常性研究チーム, 上級研究員 (60385698)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: インスリン受容体基質2 / 摂食調節 / 糖産生

Outline of Final Research Achievements

Brain-specific insulin receptor substrate (Irs)-2 knockout mice (NIrs2KO mice) displayed obesity, hyperphagia and insulin resistance both in the liver and the skeletal muscle. Since those phenotypes are augmented by obesity, we adopted pair-feeding to maintain body weights of NIrs2KO mice equal to control mice. Even in pair-fed NIrs-2KO mice, hepatic glucose production was impaired and a food intake was accelerated, suggesting that hepatic insulin resistance and hyperphagia observed in NIrs2KO mice were independent of obesity.
It has been shown that insulin signal in the CNS increased IL-6 expression and subsequently induced phosphorylation of Stat3 associated with decreased expression levels of gluconeogenic genes in the liver, we found that Irs2 in the CNS might contribute to this pathway. We also found that Irs2 in the CNS might play an important role in the regulation of food intake by insulin and leptin.

Free Research Field

糖尿病