Analyses of effects of beta-cell disallowed genes on glucose metabolism

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K08915
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: International University of Health and Welfare
• Principal Investigator: Nishimura Wataru 国際医療福祉大学, 医学部, 教授 (00334433)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 発生・分化 / 遺伝子 / 糖尿病 / 発現制御 / 膵β細胞 / インスリン / 脱分化 / 成熟分化

Outline of Final Research Achievements

Pancreatic β-cells regulate glucose metabolism by secreting insulin. Dysfunction of β-cells results in diabetes. We have previously demonstrated dedifferentiation of β-cells in diabetes model mice by lineage tracing studies. In dedifferentiated β-cells, expression of particular genes, which is inhibited in mature β-cells, is upregulated. In this study, we identified a group of genes whose expression is specifically inhibited in mature β-cells by comprehensive gene expression analyses. Results of functional analysis of these genes revealed that upregulation in expression of these genes in impaired β-cells under diabetes is induced by several transcription factors, whose expression is also upregulated in impaired β-cells. We also elucidated that these genes can influence the interaction between β-cells and the microenvironment around pancreatic islets. These results suggested that factors identified in this study can be molecular targets for improvement of β-cell function.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

これまでの生物学の研究では主に、成熟した細胞に発現して、生理的に重要な機能を持つ遺伝子と、それらの病態における発現変動が、解析対象とされてきた。これに対して、近年の遺伝子発現解析技術の発達は、特定の細胞特異的に発現が抑制される遺伝子を解析対象とすることを可能にした。細胞機能と遺伝子発現との関連を解析する上で、膵β細胞は機能のアッセイ系やマーカー分子が確立しており、対象として扱いやすい。本研究課題では、成熟膵β細胞特異的に発現が抑制されている遺伝子群の機能を解析し、発現抑制の破綻と膵β細胞障害との関連について分子レベルで一定の知見を得ており、学術的に意義ある研究成果といえる。