Mitochondrial dysfunction and increased reactive oxygen species impair insulin secretion in sphingomyelin synthase 1-null Mice

Yano, Masato; Watanabe, Ken; Yamamoto, Tadashi; Ikeda, Kazutaka; Senokuchi, Takafumi; Lu, Meihong; Kadomatsu, Tsuyoshi; Tsukano, Hiroto; Ikawa, Masahito; Okabe, Masaru; Yamaoka, Shohei; Okazaki, Toshiro; Umehara, Hisanori; Gotoh, Tomomi; Song, Wen Jie; Node, Koichi; Taguchi, Ryo; Yamagata, Kazuya; Oike, Yuichi

doi:https://doi.org/10.1074/jbc.M110.179176

Mitochondrial dysfunction and increased reactive oxygen species impair insulin secretion in sphingomyelin synthase 1-null Mice

Yano, Masato; Watanabe, Ken; Yamamoto, Tadashi et al.

Journal of Biological Chemistry, 2011, 286(5), 3992-4002

Number of Access:1,922（2025-08-22 01:06 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/78614

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Title	Mitochondrial dysfunction and increased reactive oxygen species impair insulin secretion in sphingomyelin synthase 1-null Mice
Creator	CreatorName Yano, Masato
	NRID 1000010342966 1000010342966 CreatorName Watanabe, Ken
	NRID 1000080762187 1000080762187 CreatorName Yamamoto, Tadashi
	CreatorName Ikeda, Kazutaka
	NRID 1000000530320 1000000530320 CreatorName Senokuchi, Takafumi
	CreatorName Lu, Meihong
	NRID 1000090555757 1000090555757 CreatorName Kadomatsu, Tsuyoshi
	CreatorName Tsukano, Hiroto
	NRID 1000020304066 1000020304066 ORCID 0000-0001-9859-6217 0000-0001-9859-6217 researchmap permalink read0054910 read0054910 Scopus Author ID 16689054500 16689054500 CreatorName Ikawa, Masahito
	NRID 1000030089875 1000030089875 CreatorName Okabe, Masaru
	CreatorName Yamaoka, Shohei
	NRID 1000040233308 1000040233308 CreatorName Okazaki, Toshiro
	CreatorName Umehara, Hisanori
	CreatorName Gotoh, Tomomi
	CreatorName Song, Wen Jie
	NRID 1000080359950 1000080359950 CreatorName Node, Koichi
	NRID 1000020080210 1000020080210 CreatorName Taguchi, Ryo
	CreatorName Yamagata, Kazuya
	NRID 1000090312321 1000090312321 CreatorName Oike, Yuichi
Description	Masato Yano, Ken Watanabe, Tadashi Yamamoto, Kazutaka Ikeda, Takafumi Senokuchi, Meihong Lu, Tsuyoshi Kadomatsu, Hiroto Tsukano, Masahito Ikawa, Masaru Okabe, Shohei Yamaoka, Toshiro Okazaki, Hisanori Umehara, Tomomi Gotoh, Wen-Jie Song, Koichi Node, Ryo Taguchi, Kazuya Yamagata, Yuichi Oike, Mitochondrial Dysfunction and Increased Reactive Oxygen Species Impair Insulin Secretion in Sphingomyelin Synthase 1-null Mice, Journal of Biological Chemistry, Volume 286, Issue 5, 2011, Pages 3992-4002, ISSN 0021-9258, https://doi.org/10.1074/jbc.M110.179176.
Abstract	Sphingomyelin synthase 1 (SMS1) catalyzes the conversion of ceramide to sphingomyelin. Here, we generated and analyzed SMS1-null mice. SMS1-null mice exhibited moderate neonatal lethality, reduced body weight, and loss of fat tissues mass, suggesting that they might have metabolic abnormality. Indeed, analysis on glucose metabolism revealed that they showed severe deficiencies in insulin secretion. Isolated mutant islets exhibited severely impaired ability to release insulin, dependent on glucose stimuli. Further analysis indicated that mitochondria in mutant islet cells cannot up-regulate ATP production in response to glucose. We also observed additional mitochondrial abnormalities, such as hyperpolarized membrane potential and increased levels of reactive oxygen species (ROS) in mutant islets. Finally, when SMS1-null mice were treated with the anti-oxidant N-acetyl cysteine, we observed partial recovery of insulin secretion, indicating that ROS overproduction underlies pancreatic β-cell dysfunction in SMS1-null mice. Altogether, our data suggest that SMS1 is important for controlling ROS generation, and that SMS1 is required for normal mitochondrial function and insulin secretion in pancreatic β-cells.
Publisher	American Society for Biochemistry and Molecular Biology
Source Title	Journal of Biological Chemistry
Volume (Issue)	286(5)
Page	3992-4002
Date of Issued	2011-02-04
Language	English
Handle URL	https://hdl.handle.net/11094/78614
PISSN	00219258
eISSN	1083351X
NCID	AA1202441X
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1074/jbc.M110.179176
Relation.isIdenticalTo	PMID 21115496
Access Rights	open access
CopyRight	© 2011 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology. This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCTERMS.bibliographicCitation	Journal of Biological Chemistry. 2011, 286(5), p. 3992-4002
DC.title	Mitochondrial dysfunction and increased reactive oxygen species impair insulin secretion in sphingomyelin synthase 1-null Mice
DC.creator	Yano, Masato
	Watanabe, Ken
	Yamamoto, Tadashi
	Ikeda, Kazutaka
	Senokuchi, Takafumi
	Lu, Meihong
	Kadomatsu, Tsuyoshi
	Tsukano, Hiroto
	Ikawa, Masahito
	Okabe, Masaru
	Yamaoka, Shohei
	Okazaki, Toshiro
	Umehara, Hisanori
	Gotoh, Tomomi
	Song, Wen Jie
	Node, Koichi
	Taguchi, Ryo
	Yamagata, Kazuya
	Oike, Yuichi
DC.publisher	American Society for Biochemistry and Molecular Biology
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2011-02-04
DC.identifier	https://doi.org/10.1074/jbc.M110.179176
DC.description	Masato Yano, Ken Watanabe, Tadashi Yamamoto, Kazutaka Ikeda, Takafumi Senokuchi, Meihong Lu, Tsuyoshi Kadomatsu, Hiroto Tsukano, Masahito Ikawa, Masaru Okabe, Shohei Yamaoka, Toshiro Okazaki, Hisanori Umehara, Tomomi Gotoh, Wen-Jie Song, Koichi Node, Ryo Taguchi, Kazuya Yamagata, Yuichi Oike, Mitochondrial Dysfunction and Increased Reactive Oxygen Species Impair Insulin Secretion in Sphingomyelin Synthase 1-null Mice, Journal of Biological Chemistry, Volume 286, Issue 5, 2011, Pages 3992-4002, ISSN 0021-9258, https://doi.org/10.1074/jbc.M110.179176.
DCTERMS.abstract	Sphingomyelin synthase 1 (SMS1) catalyzes the conversion of ceramide to sphingomyelin. Here, we generated and analyzed SMS1-null mice. SMS1-null mice exhibited moderate neonatal lethality, reduced body weight, and loss of fat tissues mass, suggesting that they might have metabolic abnormality. Indeed, analysis on glucose metabolism revealed that they showed severe deficiencies in insulin secretion. Isolated mutant islets exhibited severely impaired ability to release insulin, dependent on glucose stimuli. Further analysis indicated that mitochondria in mutant islet cells cannot up-regulate ATP production in response to glucose. We also observed additional mitochondrial abnormalities, such as hyperpolarized membrane potential and increased levels of reactive oxygen species (ROS) in mutant islets. Finally, when SMS1-null mice were treated with the anti-oxidant N-acetyl cysteine, we observed partial recovery of insulin secretion, indicating that ROS overproduction underlies pancreatic β-cell dysfunction in SMS1-null mice. Altogether, our data suggest that SMS1 is important for controlling ROS generation, and that SMS1 is required for normal mitochondrial function and insulin secretion in pancreatic β-cells.
DC.rights	© 2011 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology. This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	78614
citation_title	Mitochondrial dysfunction and increased reactive oxygen species impair insulin secretion in sphingomyelin synthase 1-null Mice
citation_author	Yano, Masato
	Watanabe, Ken
	Yamamoto, Tadashi
	Ikeda, Kazutaka
	Senokuchi, Takafumi
	Lu, Meihong
	Kadomatsu, Tsuyoshi
	Tsukano, Hiroto
	Ikawa, Masahito
	Okabe, Masaru
	Yamaoka, Shohei
	Okazaki, Toshiro
	Umehara, Hisanori
	Gotoh, Tomomi
	Song, Wen Jie
	Node, Koichi
	Taguchi, Ryo
	Yamagata, Kazuya
	Oike, Yuichi
citation_publisher	American Society for Biochemistry and Molecular Biology
citation_language	English
citation_date	2011-02-04
citation_journal_title	Journal of Biological Chemistry
citation_volume	286
citation_issue	5
citation_firstpage	3992
citation_lastpage	4002
citation_doi	https://doi.org/10.1074/jbc.M110.179176
citation_pmid	21115496
citation_public_url	https://hdl.handle.net/11094/78614

Mitochondrial dysfunction and increased reactive oxygen species impair insulin secretion in sphingomyelin synthase 1-null Mice

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