Pancreatic β Cell-specific Expression of Thioredoxin, an Antioxidative and Antiapoptotic Protein, Prevents Autoimmune and Streptozotocin-induced Diabetes

Hotta, Mizuo; Tashiro, Fumi; Ikegami, Hiroshi; Niwa, Hitoshi; Ogihara, Toshio; Yodoi, Junji; Miyazaki, Jun-ichi

doi:https://doi.org/10.1084/jem.188.8.1445

アクセス数:269件（2024-04-20 15:04 集計）

固定URL: https://hdl.handle.net/11094/23106

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タイトル	Pancreatic β Cell-specific Expression of Thioredoxin, an Antioxidative and Antiapoptotic Protein, Prevents Autoimmune and Streptozotocin-induced Diabetes
著者	著者名 Hotta, Mizuo
	NRID 1000040136213 1000040136213 researchmap permalink read0184420 read0184420 Scopus Author ID 35397831100 35397831100 著者名 Tashiro, Fumi
	NRID 1000020221062 1000020221062 著者名 Ikegami, Hiroshi
	NRID 1000080253730 1000080253730 著者名 Niwa, Hitoshi
	NRID 1000060107042 1000060107042 著者名 Ogihara, Toshio
	NRID 1000080108993 1000080108993 著者名 Yodoi, Junji
	NRID 1000080229830 1000080229830 著者名 Miyazaki, Jun-ichi
キーワード等	oxidative stress
	nonobese diabetic mouse
	insulitis
	cytokine
	apoptosis
抄録	The cytotoxicity of reactive oxygen intermediates (ROIs) has been implicated in the destruction of pancreatic β cells in insulin-dependent diabetes mellitus (IDDM). Thioredoxin (TRX), a redox (reduction/oxidation)-active protein, has recently been shown to protect cells from oxidative stress and apoptosis. To elucidate the roles of oxidative stress in the development of autoimmune diabetes in vivo, we produced nonobese diabetic transgenic mice that overexpress TRX in their pancreatic β cells. In these transgenic mice, the incidence of diabetes was markedly reduced, whereas the development of insulitis was not prevented. Moreover, induction of diabetes by streptozotocin, an ROI-generating agent, was also attenuated by TRX overexpression in β cells. This is the first direct demonstration that an antioxidative and antiapoptotic protein protects β cells in vivo against both autoimmune and drug-induced diabetes. Our results strongly suggest that oxidative stress plays an essential role in the destruction of β cells by infiltrating inflammatory cells in IDDM.
出版者	The Rockefeller University Press
収録物名	Journal of Experimental Medicine
巻(号)	188(8)
ページ	1445-1451
刊行年月	1998-10-19
言語	英語
ハンドルURL	https://hdl.handle.net/11094/23106
PISSN	00221007
NCID	AA00697559
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1084/jem.188.8.1445
アクセス権	open access
権利情報	© 1998 Rockefeller University Press
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	Journal of Experimental Medicine. 1998, 188(8), p. 1445-1451
DC.title	Pancreatic β Cell-specific Expression of Thioredoxin, an Antioxidative and Antiapoptotic Protein, Prevents Autoimmune and Streptozotocin-induced Diabetes
DC.creator	Hotta, Mizuo
	Tashiro, Fumi
	Ikegami, Hiroshi
	Niwa, Hitoshi
	Ogihara, Toshio
	Yodoi, Junji
	Miyazaki, Jun-ichi
DC.publisher	The Rockefeller University Press
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	1998-10-19
DC.identifier	https://doi.org/10.1084/jem.188.8.1445
DC.subject	oxidative stress
	nonobese diabetic mouse
	insulitis
	cytokine
	apoptosis
DCTERMS.abstract	The cytotoxicity of reactive oxygen intermediates (ROIs) has been implicated in the destruction of pancreatic β cells in insulin-dependent diabetes mellitus (IDDM). Thioredoxin (TRX), a redox (reduction/oxidation)-active protein, has recently been shown to protect cells from oxidative stress and apoptosis. To elucidate the roles of oxidative stress in the development of autoimmune diabetes in vivo, we produced nonobese diabetic transgenic mice that overexpress TRX in their pancreatic β cells. In these transgenic mice, the incidence of diabetes was markedly reduced, whereas the development of insulitis was not prevented. Moreover, induction of diabetes by streptozotocin, an ROI-generating agent, was also attenuated by TRX overexpression in β cells. This is the first direct demonstration that an antioxidative and antiapoptotic protein protects β cells in vivo against both autoimmune and drug-induced diabetes. Our results strongly suggest that oxidative stress plays an essential role in the destruction of β cells by infiltrating inflammatory cells in IDDM.
DC.rights	© 1998 Rockefeller University Press
DC.format	application/pdf
citation_title	Pancreatic β Cell-specific Expression of Thioredoxin, an Antioxidative and Antiapoptotic Protein, Prevents Autoimmune and Streptozotocin-induced Diabetes
citation_author	Hotta, Mizuo
	Tashiro, Fumi
	Ikegami, Hiroshi
	Niwa, Hitoshi
	Ogihara, Toshio
	Yodoi, Junji
	Miyazaki, Jun-ichi
citation_publisher	The Rockefeller University Press
citation_language	英語
citation_date	1998-10-19
citation_journal_title	Journal of Experimental Medicine
citation_volume	188
citation_issue	8
citation_firstpage	1445
citation_lastpage	1451
citation_doi	https://doi.org/10.1084/jem.188.8.1445
citation_public_url	https://hdl.handle.net/11094/23106

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