Development of anti-diabetic therapy by the elucidation of the mechanism linking microflora and adipose tissue macrophages

2016 Fiscal Year Final Research Report

• Project/Area Number: 16K15488
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: The University of Tokyo
• Principal Investigator: Ueki Kohjiro 東京大学, 医学部附属病院, 客員研究員 (00396714)
• Project Period (FY): 2016-04-01 – 2017-03-31
• Keywords: Akt / マクロファージ / インスリン / LPS

Outline of Final Research Achievements

We have found that LPS derived from microflora and insulin induced by feeding stimulates the production of IL-10 in adipose tissue macrophages, and that this production depends on the Akt-mTORC1 pathway. Indeed, mice with disiruption of Akt1 and Akt2 specifically in macrophage (MAktDKO mice) show impaired production of IL-10. MAktDKO mice exhibit impaired glucose tolerance with increased hepatic gluconeogenesis. Adenovirus-mdeiated gene transfer of IL-10 improves glucose tolerance with decreased hepatic gluconeogenesis in MAktDKO mice. Furthermore, MAktDKO mice show more weight gain under the normal chow diet compared to the control mice.

Free Research Field

糖尿病代謝内科学