Addressing the role of CD36 in insulin secretion and diabetes incidence using a new mouse model

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K23872
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0803:Pathology, infection/immunology, and related fields
• Research Institution: Nippon Medical School
• Principal Investigator: NAGAO Mototsugu 日本医科大学, 医学部, 講師 (10468762)
• Project Period (FY): 2019-08-30 – 2022-03-31
• Keywords: 2型糖尿病 / インスリン分泌能 / β細胞 / CD36 / エキソサイトーシス / Oikawa-Nagaoマウス

Outline of Final Research Achievements

Hereditary insulin secretion capacity can be a crucial determinant for the susceptibility to type 2 diabetes. However, its molecular background has not been fully clarified. We previously demonstrated that overexpression of fatty acid translocase/CD36 impaired insulin secretion, associated with suppressed insulin signaling and exocytosis dysfunction (e.g., defects in insulin granule docking), in INS-1 clonal β-cells. In the present study, we aimed to study the implications of CD36 expression for hereditary low insulin secretion capacity observed in diabetes-prone ON-DP mice. We demonstrated here that the ON-DP mouse islets (and β-cells) had abnormally high CD36 protein expression and showed lipid accumulation, insulin signaling attenuation, and defects in insulin granule docking. These findings provide new insight into the pathophysiological role of CD36 for the development of T2D.

Free Research Field

実験病理学

Academic Significance and Societal Importance of the Research Achievements

我々が行った肥満ドナー由来のヒト膵島を用いた検討において、非２型糖尿病者（正常血糖者）と比較して、２型糖尿病患者ではエキソサイトーシス障害やインスリン分泌能の低下がみられるのと同時に、CD36発現が遺伝子およびタンパク質レベルで高いことを見出している。ON-DPマウスの膵島（β細胞）において肥満２型糖尿病患者の膵島と類似した事象を確認し得た本研究の成果は、ON-DPマウスの「2型糖尿病発症における膵島病理基盤モデル」としての位置づけをより確かなものとすると共に、β細胞のCD36を標的とする新たな糖尿病予防・治療法開発に繋がる基礎的知見となるものと考えられる。