Establishment of novel therapeutic strategies for diabetes by increasing pancreatic beta-cell mass through targeting of intracellular lipid signaling

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K11512
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: University of Shizuoka
• Principal Investigator: KANEKO Yukiko 静岡県立大学, 薬学部, 講師 (00381038)
• Co-Investigator(Kenkyū-buntansha): 石川 智久 静岡県立大学, 薬学部, 教授 (10201914)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 糖尿病 / インスリン分泌 / 膵β細胞 / ジアシルグリセロールキナーゼ

Outline of Final Research Achievements

Although a loss of β-cell mass is observed in both type 1 and type 2 diabetes, there are no clinical therapeutics for diabetes that target β-cell proliferation. The present study was designed based on our findings that DGKδ-deficient mice show improved glucose tolerance and suppression of diabetes progression by increasing the number of pancreatic islets. The present study demonstrated that β-cell-specific knockout of DGKδ, rather than indirect effects of non-specific DGKδ knockout in other tissues such as the brain, leads to islet proliferation in vivo, and that proliferating islets are composed of mature β-cells. Our findings also provide insight into the regulation of DGKδ localization in pancreatic β-cells. This study suggests that regulating the expression and localization of DGKδ could be a potential target for novel therapeutics for diabetes via β-cell proliferation.

Free Research Field

薬理学、糖尿病学

Academic Significance and Societal Importance of the Research Achievements

β細胞量の回復は糖尿病の根本治療になり得るものの、β細胞は胎生期以降ほとんど増殖せず、成体期にβ細胞増殖を惹起させるのは困難である。したがって、これまでにβ細胞増殖を標的とした治療薬はない。本研究において、β細胞特異的にDGKδを欠損させると成熟したβ細胞、すなわちグルコース濃度に応じインスリンを分泌し得るβ細胞が増殖することを証明し、DGKδがβ細胞増殖を標的とした新規糖尿病治療薬としての可能性が明らかとなった。本研究成果は病態生理学的意義だけでなく、今後の糖尿病治療薬の開発にも貢献しうる。