Environmental factor for diabetes, non-insulin-dependent diabetes by virus infection

糖尿病的环境因素、病毒感染引起的非胰岛素依赖型糖尿病

• 批准号: 13671174
• 负责人: UTSUGI Toshihiro
• 金额: $ 2.24万
• 依托单位: Gunma university
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671174/
• 关键词: Virus-induced diabetes; EMC virus; Mature lymphocyte; islet cells; knockout mouse; アポトーシス; パーフォリン

Virus infection to pancreatic beta cells could be one of environmental factors for the development of diabetes due to dysfunction of pancreatic beta cells. We developed the new animal model for non-insulin dependent diabetes mellitus by infection of the NDK25 variant of encephalomyocarditis (EMC) virus. To study the roles of mature cellular immunity on the pathogenesis of this model, RAG-2 knockout (KO) mice were infected with the NDK25 variant of EMCV. The original strain, 129/SvEv mouse was used as control. Glucose intolerance was observed in RAG-2KO, but not in control. Histological study showed that the pancreatic islets were mildly destroyed and the virus genome was detected in the islets in RAG-2KO, whereas the pancreatic islets appeared normal in control. Secondly, to elucidate roles of each lymphocyte subset in this model, MHC class II deficient mice, MHC class I deficient mice, and B-cell deficient mice, were infected with the NDK25 of EMCV. No mice showed glucose intolerance, and histological study demonstrated normal appearance of pancreatic islets in these mice.From these results, we conclude that mature cellular immunity play a protective role against viral infection on the pathogenesis of glucose intolerance, and, once infected, the destruction of pancreatic beta cells by EMCV depends on their own ability to destroy beta cells

病毒感染胰岛β细胞可能是由于胰岛β细胞功能障碍导致糖尿病发生的环境因素之一。我们建立了感染NDK25变种脑心肌炎(EMC)病毒的新的非胰岛素依赖型糖尿病动物模型。为了研究成熟细胞免疫在该模型发病机制中的作用，用NDK25变异型EMCV感染RAG-2基因敲除(KO)小鼠。以原始品系129/SvEv小鼠为对照。RAG-2KO组可观察到糖耐量异常，而对照组则未见。组织学检查显示，RAG-2KO组大鼠胰岛轻度破坏，胰岛内可见病毒基因组，而对照组胰岛正常。其次，为了阐明各淋巴细胞亚群在该模型中的作用，分别用EMCV的NDK25感染MHC II类缺陷小鼠、MHC I类缺陷小鼠和B细胞缺陷小鼠。这些结果表明，成熟的细胞免疫在糖耐量低减的发病机制中起保护作用，一旦感染，EMCV对胰岛细胞的破坏依赖于它们自身对胰岛细胞的破坏能力

项目成果

Okuno S., Utsugi T., et.al.: "Angiotensin-converting enzyme gene polymorphism is a potent risk factor for developing microalbuminuria in Japanese patients with type2 Diabetes mellitus"J of International Medical Research. 31, in press.

Okuno S.、Utsugi T. 等人：“血管紧张素转换酶基因多态性是日本 2 型糖尿病患者出现微量白蛋白尿的一个潜在危险因素”《国际医学研究杂志》。

Ito H., Utsugi T., et.al.: "Angiotensin-converting enzyme insertion/deletion polymorphism and polyneuropathy in type 2 diabetes without macroalbuminuna"J of International Medical Research. 30. 476-482 (2002)

Ito H.、Utsugi T.等人：“无大白蛋白的 2 型糖尿病中血管紧张素转换酶插入/缺失多态性和多神经病”《国际医学研究杂志》。

Ito Y., Utsugi T., et al.: "Angiotensin-converting enzyme insertion/deletion polymorphism and polyneuropathy in type 2 diabetes without macroalbuminuria"J of International Medical Research. 30. 476-482 (2002)

Ito Y.、Utsugi T. 等人：“血管紧张素转换酶插入/缺失多态性和无大量白蛋白尿的 2 型糖尿病中的多发性神经病”《国际医学研究杂志》。

Amrani A., Utsugi T.: "Perforin-independent Beta cell destruction by diabetogenic CD8+T lymphocytes in transgenic nonobese diabetic mice"J Clin Invest. 103. 1201-1209 (1999)

Amrani A.、Utsugi T.：“转基因非肥胖糖尿病小鼠中致糖尿病 CD8 T 淋巴细胞对穿孔素独立的 Beta 细胞的破坏”J Clin Invest。

Utsugi T., Kanda T., et.al.: "Perforin play a beta-cell cytotoxic role on the pathogenesis of NIDDM induced by virus infection"Diabetologia. 42. A103 (1999)

Utsugi T.、Kanda T.等人：“穿孔素在病毒感染诱导的 NIDDM 发病机制中发挥β细胞细胞毒作用”Diabetologia。