Pancreatic islet pathological changes, clinical course, and prognostic prediction based on type 2 diabetes susceptibility gene polymorphism

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K08462
• 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: Hirosaki University
• Principal Investigator: Mizukami Hiroki 弘前大学, 医学研究科, 教授 (00374819)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: ２型糖尿病 / 膵臓 / 膵島 / β細胞 / 一塩基多型

Outline of Final Research Achievements

1. SNPs analysis: 111 autopsy cases (32 type 2 diabetes cases, 79 non-type 2 diabetes cases) from Hirosaki University were selected. Genomic DNA was extracted from liver and kidney tissues collected at autopsy. After confirming the quality of the DNA, the Japonica array (Toshiba) comprehensively examined the SNPs of the DNA.
2. Pathological analysis: Pancreatic islet cell/amyloid volume and cell dynamics are analyzed. Using pancreatic slices, (1) each endocrine cell volume of pancreatic islets, (2) proliferation of islet cells, (3) islet cell death, and (4) pancreatic cell neogenesis were evaluated.
Similar to previous reports, we found decreased β-cell volume, increased α-cell volume, and increased islet neogenesis in type 2 diabetes.

Free Research Field

病理学

Academic Significance and Societal Importance of the Research Achievements

本研究において剖検組織を用いて膵島の病理学的変化と遺伝学的変化を相関させる試みを行った。病理学的検索により、糖尿病検体では膵β細胞容積の減少、分化転換の増加が認められた。遺伝子学的検索では、東芝のジャポニカアレーで１００症例以上の剖検検体のSNPデータを得ることができた。これら病理学的データ、SNPデータは現在解析中であるが、病理学的変化との関連が得ることができれば、本邦における２型糖尿病の新たな病態の解明につながる可能性がある。さらに、遺伝子変化を標的とした新規治療も期待される。