学術雑誌論文

学術雑誌論文

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

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

American Society for Biochemistry and Molecular Biology

英語

2011-02-04

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

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.

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.

© 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.

78614

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

American Society for Biochemistry and Molecular Biology

英語

2011-02-04

Journal of Biological Chemistry

286

5

3992

4002

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

21115496

https://hdl.handle.net/11094/78614