Regulation of insulin secretion by sphingolipids

2010 Fiscal Year Final Research Report

• Project/Area Number: 21790286
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: General medical chemistry
• Research Institution: Kumamoto University
• Principal Investigator: YANO Masato Kumamoto University, 大学院・生命科学研究部, 助教 (60315299)
• Project Period (FY): 2009 – 2010
• Keywords: スフィンゴ脂質 / セラミド / インスリン / 酸化ストレス / ミトコンドリア

Research Abstract

Sphingomyelin synthase 1 (SMS1) catalyzes the conversion of ceramide to sphingomyelin, and has a central role in controlling sphingolipid homeostasis in the cell. In this study, we analyzed the pathogenesis of SMS1 null mice, which exhibit insulin secretion deficiency. As results, we found that disturbance of sphingolipid homeostasis and increased oxidative stress accompanied with mitochondrial dysfunction underlies insulin secretion deficiency observed in pancreatic beta-cells of SMS1 null mice. Furthermore, anti-oxidant treatment recovered insulin secretion deficiency in SMS1 null mice.

Research Products

• [Journal Article] Mitochondrial Dysfunction and Increased Reactive Oxygen Species Impair Insulin Secretion in Sphingomyelin Synthase 1-null Mice. (2011)
  • Author(s): 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.
  • Journal Title: The Journal of Biological Chemistry 286 Pages: 3992-4002
  • Peer Reviewed
• [Journal Article] The Endoplasmic Reticulum Stress-C/EBP Homologous Protein Pathway-Mediated Apoptosis in Macrophages Contributes to the Instability of Atherosclerotic Plaques. (2010)
  • Author(s): Hiroto Tsukano, Tomomi Gotoh, Motoyoshi Endo, Keishi Miyata, Hirokazu Tazume, Tsuyoshi Kadomatsu, Masato Yano, Takao Iwawaki, Kenji Kohno, Kimi Araki, Hiroshi Mizuta, Yuichi Oike.
  • Journal Title: Arteriosclerosis, Thrombosis, and Vascular Biology 30 Pages: 1925-1932
  • Peer Reviewed
• [Presentation] スフィンゴミエリン合成酵素1ノックアウトマウスにおけるROS産生増加と致死性・インスリン分泌不全・脂肪萎縮との関連性の解析 (2010)
  • Author(s): 矢野正人、山本格士、渡部研、池田和貴、瀬ノ口隆文、門松毅、束野寛人、後藤知己、岡崎俊朗、田口良、山縣和也、尾池雄一
  • Organizer: 第83回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド(口頭発表およびポスター発表)
  • Year and Date: 2010-12-09
• [Presentation] スフィンゴミエリン合成酵素1による脂質および糖代謝制御に関する解析 (2009)
  • Author(s): 矢野正人、Wang Difei、池田和貴、瀬ノ口隆文、門松毅、山縣和也、田口良、渡部研、尾池雄一
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド(ポスター発表)
  • Year and Date: 2009-10-24