Development of drugs to improve insulin sensitivity by regulating M2 macrophages

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16338
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: University of Toyama
• Principal Investigator: Igarashi Yoshiko 富山大学, 学術研究部医学系, 特別研究員 (30837688)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: M2マクロファージ

Outline of Final Research Achievements

Adipose tissue-resident macrophages are the major regulators of adipocyte functions through many secretory factors. Previous reports showed that depletion of M2 macrophages promotes the proliferation of adipocyte progenitors and enhances their differentiation, contributing to the healthy expansion of adipose tissue, thus improving glucose metabolism and insulin sensitivity.
In the current study, transgenic mice were generated to examine how the proliferation of M2 macrophages regulates adipocyte progenitors’ fate and their differentiation into newly generated healthy adipocytes, ultimately regulating insulin sensitivity. Furthermore, these mice will be used to elucidate the molecular mechanisms of adipocyte progenitors’ proliferation. This study will also be a strategy for the development of drugs that can ameliorate insulin resistance by regulating M2 macrophages.

Free Research Field

代謝

Academic Significance and Societal Importance of the Research Achievements

本研究により、これまで明らかとなっていなかった脂肪細胞の分化や増殖のメカニズムを明らかとするための動物が入手できたことから、今後は肥満の脂肪組織で、病態が進行する仕組に対する理解が深まることが期待できる。また、M2マクロファージを介した、新規の糖尿病治療薬の開発についても、これまでの治療薬では治療出来ない難治性の糖尿病について効果が見られることも期待される。