2023 Fiscal Year Final Research Report
Distinct features of the pancreas in slowly progressive insulin dependent diabetes mellitus
| Project/Area Number |
21K08541
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 54040:Metabolism and endocrinology-related
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| Research Institution | Okinaka Memorial Institute for Medical Research |
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Principal Investigator |
Kobayashi Tetsuro (財)冲中記念成人病研究所, その他部局等, 研究員 (30113442)
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| Co-Investigator(Kenkyū-buntansha) |
竹下 章 (財)冲中記念成人病研究所, その他部局等, 研究員 (20322646)
水谷 哲也 東京農工大学, 農学部, 教授 (70281681)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | Enterovirus / VP1 / ２Apro / MDA5 / IFNβ / Metaplasia / PanIN / lesion |
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| Outline of Final Research Achievements |
In slowly progressive type 1 diabetes mellitus (SPIDDM), the pancreas shows sustained islet inflammation, pancreatic acinar cell metaplasia/dysplasia.
The mechanisms remain unclear.The presence of enterovirus (EV) encoded-capsid protein 1 (VP1) and -2A protease (2Apro) and the innate immune responses of the pancreas were studied using immunohistochemistry and in situ hybridization in 12 SPIDDM and 19 non-diabetic pancreases.VP1, 2Apro, and EV-RNA were detected in islets and the exocrine pancreas in all SPIDDM pancreases. Innate immune receptor, melanoma differentiation-associated gene 5 (MDA5), and interferon (IFN)-beta1 were intensified in the islets of SPIDDM patients with short disease duration. However, expressions of MDA5 and IFN-beta1were suppressed in those with longer disease duration. CD11c+ dendritic cells (DCs) in islets were scarce in long-term SPIDDM.
This study showed persistent infection of EV and suppressed innate immune responses in SPIDDM pancreas.
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| Free Research Field |
糖尿病
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| Academic Significance and Societal Importance of the Research Achievements |
EVの持続感染がSPIDDMでβ細胞の破壊と炎症、そして膵管のPanIN病変、IPMN病変、慢性膵炎に進展する可能性を考え、本研究を企画した。SPIDDMは他のサブタイプ（劇症、急性発症型）と比較してその発症頻度が高く、β細胞の残存も高頻度であり膵に感染するウイルスの分子レベルの情報を知ることでSPIDDMの病因が明らかになるばかりでなく、最終的には本疾患の進展阻止、予防にも貢献するものと考える。
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