Relationship between pancreatic beta cell dedifferentiation and NAFLD in diabetic mouse model with obesity

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K17484
• 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: Gunma University
• Principal Investigator: Ishida Emi 群馬大学, 生体調節研究所, 准教授 (80806357)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 糖尿病 / 膵β細胞機能不全 / 食事療法 / 肥満 / 脂肪肝

Outline of Final Research Achievements

In type 2 diabetes, decreased insulin secretion due to pancreatic β-cell dysfunction is a clinical problem. Pancreatic β-cell dedifferentiation has recently proposed as a cause of β-cell dysfunction in diabetes, and the authors reported that dietary restriction better prevents β-cell dedifferentiation among existing diabetes treatments in obese diabetic mice model. In the present study, we found that dietary restriction with different carbohydrate/lipid ratios differentially suppressed the progression of pancreatic β-cell dedifferentiation as well as hepatic steatosis, and we clarified one aspect of the molecular mechanism, especially in the liver. This study may contribute to the development of dietary therapy from a new perspective of preventing β-cell dedifferentiation and to the elucidation of the relationship between β-cell function, other organs and nutrients.

Free Research Field

内分泌代謝学

Academic Significance and Societal Importance of the Research Achievements

本研究は、糖尿病におけるβ細胞脱分化の進展には、摂取する栄養素、特に糖質/脂質のバランスと、肝における脂肪化が関連することを明らかにしたものであり、いまだに明らかでないβ細胞脱分化の分子メカニズムの解明や、β細胞脱分化の改善を目指した新たな食事療法の提案、β細胞脱分化と他臓器の連関など、糖尿病の発症・進行・予防や治療と密接に結びつく知見につながると考えられる。β細胞が脱分化した段階で治療介入できれば、β細胞の死滅による不可逆的なインスリン分泌不全におちいることが防がれ、インスリン自己注射などの複雑で高額な療養を要したり、進行した合併症で患者も社会も負担になることを避けたりしうると期待される。