Role of the microtubule-associated protein in insulin-dependent glucose uptake

• Project/Area Number: 24591333
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: The University of Tokushima
• Principal Investigator: SAKAUE Hiroshi 徳島大学, ヘルスバイオサイエンス研究部, 教授 (60372645)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: Adipocyte / Obesity / Diabetes / 肥満 / 糖尿病 / 脂肪細胞 / 微小管

Outline of Final Research Achievements

We identified adipocyte-specific tubulin binding protein (synuclein) in WAT of C57BL/6 mice during the development of obesity. The aim of this study is to reveal the role of synuclein in tubulin regulation in adipose tissue function. Immunofluorescence staining demonstrated that synuclein can co-localized with tubulin and enhance the staining of tubulin in 3T3-L1 adipocytes. We next examine the effect of synuclein knockdown in insulin-dependent glucose uptake and triacylglycerol (TG) accumulation in 3T3-L1 adipocytes. synuclein knockdown decreased glucose uptake, TG　accumulation and GLUT4 vesicles with plasma membrane in 3T3-L1 adipocytes. Synuclein knockout suprressed body weight gain for long term maintenance on a high-fat diet and enhance insulin sensitivity in mice. These observations suggest that synuclein can affect glucose uptake and lipid accumulation in adipose tissue by regulating tubulin polymerization.

Research Products

• [Journal Article] Sudachitin, a polymethoxylated flavone, improves glucose and lipid metabolism by increasing mitochondrial biogenesis in skeletal muscle. (2014)
  • Author(s): Tsutsumi R, Yoshida T, Nii Y, Okahisa N, Iwata S, Tsukayama M, Hashimoto R, Taniguchi Y, Sakaue H, Hosaka T, Shuto E, Sakai T.
  • Journal Title: Nutr Metab Volume: 11 Pages: 32-32
  • DOI: 10.1186/1743-7075-11-32
  • Peer Reviewed / Open Access
• [Journal Article] Enhancement of endothelial function inhibits left atrial thrombi development in an animal model of spontaneous left atrial thrombosis. (2014)
  • Author(s): Mawatari K, Yoshioka E, Toda S, Yasui S, Furukawa H, Shimohata T, Ohnishi T, Morishima M, Harada N, Takahashi A, Sakaue H, Nakaya Y.
  • Journal Title: Circ J. Volume: 78 Pages: 1980-1988
  • NAID: 130004427936
  • Peer Reviewed / Open Access
• [Journal Article] Deletion of hypoxia-inducible factor-1α in adipocytes enhances glucagon-like peptide-1 secretion and reduces adipose tissue inflammation (2014)
  • Author(s): Yoshitaka KIHIRA, Mariko MIYAKE, Manami HIRATA, Yoji HOSHINA, Kana KATO, Hitoshi SHIRAKAWA, Hiroshi SAKAUE, Noriko YAMANO, Yuki IZAWA-ISHIZAWA, Keisuke ISHIZAWA, Yasumasa IKEDA, Koichiro TSUCHIYA, Toshiaki TAMAKI, Shuhei TOMITA
  • Journal Title: PLoS One. Volume: 9
  • DOI: 10.1371/journal.pone.0093856
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Albumin-normalized serum zinc: a clinically useful parameter for detecting taste impairment in patients undergoing dialysis. (2014)
  • Author(s): Tsutsumi R, Ohashi K, Tsutsumi YM, Horikawa YT, Minakuchi J, Minami S, Harada N, Sakaue H, Sakai T, Nakaya Y.
  • Journal Title: Nutr Res. Volume: 34 Pages: 11-16
  • DOI: 10.1016/j.nutres.2013.10.009
  • Peer Reviewed / Open Access
• [Journal Article] Cysteine string protein 1 (CSP1) modulates insulin sensitivity by attenuating glucose transporter 4 (GLUT4) vesicle docking with the plasma membrane. (2014)
  • Author(s): Jambaldorj B, Terada E, Hosaka T, Kishuku Y, Tomioka Y, Iwashima K, Hirata Y, Teshigawara K, Thi Kim Le C, Nakagawa T, Harada N, Sakai T, Sakaue H, Matsumoto T, Funaki M, Takahashi A, Nakaya Y.
  • Journal Title: J Med Invest. Volume: 60 Pages: 197-204
  • NAID: 130004822683
  • Peer Reviewed
• [Journal Article] Exendin-4, a glucagon-like peptide-1 receptor agonist, attenuates neointimal hyperplasia after vascular injury. (2013)
  • Author(s): Y. Hirata, H. Kurobe, C. Nishio, K. Tanaka, D. Fukuda, E. Uematsu, S. Nishimoto, T. Soeki, N. Harada, H. Sakaue, T. Kitagawa, M. Shimabukuro, N. Nakaya, M. Sata
  • Journal Title: Eur J Pharmacol. Volume: 699 Pages: 106-111
  • DOI: 10.1016/j.ejphar.2012.11.057
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Telmisartan Ameliorates Insulin Sensitivity by Acting the AMPK/SIRT1 Pathway in Skeletal Muscle of Obese db/db Mice (2013)
  • Author(s): Shiota A, Shimabukuro M, Fukuda D, Soeki T, Sato H, Uematsu E, Hirata Y, Kurobe H, Maeda N, Sakaue H, Masuzaki H, Shimomura I, Sata M.
  • Journal Title: Cardiovasc Diabetol. Volume: 11 Pages: 139-139
  • DOI: 10.1186/1475-2840-11-139
  • Peer Reviewed
• [Journal Article] Proliferative and antiapoptotic signaling stimulated by nuclear-localized PDK1 results in oncogenesis. (2012)
  • Author(s): Kikani CK, et al.
  • Journal Title: Sci Signal. Volume: 5 Pages: 249-249
  • DOI: 10.1126/scisignal.2003065
  • Peer Reviewed
• [Journal Article] Activation of AMPK-Sirt1 Pathway by Telmisartan in White Adipose Tissue: A Possible Link to Anti-metabolic Effects (2012)
  • Author(s): Shiota A, Shimabukuro M, Fukuda D, Soeki T, Sato H, Uematsu E, Hirata Y, Kurobe H, Sakaue H, Nakaya Y, Masuzaki H, Sata M
  • Journal Title: Eur J Pharmacol. Volume: 692 Pages: 84-90
  • DOI: 10.1016/j.ejphar.2012.07.026
  • Peer Reviewed
• [Journal Article] Identification and functional characterization of human glycerol-3-phosphate acyltransferase 1 gene promoters. (2012)
  • Author(s): Harada N, Fujimoto E, Okuyama M, Sakaue H, Nakaya Y
  • Journal Title: Biochem Biophys Res Commun. Volume: 423 Pages: 128-133
  • DOI: 10.1016/j.bbrc.2012.05.094
  • Peer Reviewed
• [Journal Article] Ablation of 3-phosphoinositide-dependent protein kinase 1 (PDK1) in vascular endothelial cells enhances insulin sensitivity by reducing visceral fat and suppressing angiogenesis. (2012)
  • Author(s): Tawaramoto K, Sakaue H, et al
  • Journal Title: Mol Endocrinol. Volume: Vol.26 Pages: 95-109
  • DOI: 10.1210/me.2010-0412
  • Peer Reviewed
• [Journal Article] 【エネルギー消費と代謝障害】 運動とエネルギー消費 (2012)
  • Author(s): 阪上 浩
  • Journal Title: 糖尿病 Volume: 55 Pages: 306-308
• [Presentation] TBP, Adipocyte-specific Tubulin-Binding Protein, Can Control Cytoskeletal Structure, and Insulin Stimulated Glucose Uptake. (2015)
  • Author(s): Masashi Kuroda and Hiroshi Sakaue
  • Organizer: 75th Scientific Session of American diabetes association.
  • Place of Presentation: ボストンコンベンションセンター（Boston）, USA
  • Year and Date: 2015-06-05 – 2015-06-09
• [Presentation] 細胞骨格制御分子γ-synucleinによる糖取り込み機構の解析 (2014)
  • Author(s): 黒田雅士、阪上浩
  • Organizer: 第３５回日本肥満学会
  • Place of Presentation: シーガイヤコンベンションセンター（福岡県福岡市）、日本
  • Year and Date: 2014-10-24 – 2014-10-25
• [Presentation] Role of the new microtubule-associated protein in the development of obesity (2013)
  • Author(s): Okitsu R, Sakaue H
  • Organizer: 国際肥満学会
  • Place of Presentation: Kuala Lumpur, Malaysia(Convention Centre)
• [Presentation] Role of DNA methylation for Leptin Gene Promoter in 3T3-L1 Adipocytes (2013)
  • Author(s): Kuroda M, Sakaue H
  • Organizer: 国際肥満学会
  • Place of Presentation: Kuala Lumpur, Malaysia(Convention Centre)
• [Presentation] Role of DNA methylation for Leptin Gene Promoter in 3T3-L1 Adipocytes (2013)
  • Author(s): Kuroda M, Sakaue H
  • Organizer: 米国糖尿病学会
  • Place of Presentation: Cicago, USA（McCormick Place）
• [Presentation] 細胞骨格制御分子による糖取り込み機構の解析 (2013)
  • Author(s): 興津 理絵, 阪上 浩
  • Organizer: 日本肥満学会
  • Place of Presentation: 東京都（国際フォーラム）
• [Presentation] 細胞骨格制御分子による糖取り込み機構の解析 (2013)
  • Author(s): 興津 理絵, 阪上 浩
  • Organizer: 日本糖尿病学会
  • Place of Presentation: 熊本（ホテル日航熊本）
• [Presentation] レプチン発現制御機構を検討し得る培養脂肪細胞の作製 (2012)
  • Author(s): 福田 亜希子, 他
  • Organizer: 日本肥満学会
  • Place of Presentation: 京都国際会館（京都府）
• [Presentation] PGC1α新規アイソフォームの肥満病態形成における役割 (2012)
  • Author(s): 野村 和弘, 他
  • Organizer: 日本肥満学会
  • Place of Presentation: 京都国際会館（京都府）
• [Presentation] 中枢神経系におけるグレリンの摂食と運動調節経路の解析 (2012)
  • Author(s): 二見 明香理, 他
  • Organizer: 日本肥満学会
  • Place of Presentation: 京都国際会館（京都府）
• [Presentation] Adipocyte turnover and its proliferation (2012)
  • Author(s): 阪上 浩
  • Organizer: 国際肥満シンポジウム
  • Place of Presentation: 京都国際会館（京都府）
  • Invited
• [Presentation] 培養脂肪細胞でのレプチン発現はDNA脱メチル化と転写因子による活性化の2つのステップで制御されている (2012)
  • Author(s): 福田 亜希子, 他
  • Organizer: 日本栄養・食糧学会大会
  • Place of Presentation: 東北大学（宮城県）
• [Book] 肥満と肥満症基礎研究の進歩 脂肪細胞の肥大と増殖 (2014)
  • Author(s): 黒田雅士、阪上浩
  • Total Pages: 728
  • Publisher: 日本臨床社
• [Book] Diabetes Strategy (2013)
  • Author(s): 黒田 雅士、阪上 浩
  • Publisher: 先端医学社
• [Book] Diabetes Strategy (2013)
  • Author(s): 阪上 浩
  • Total Pages: 19
  • Publisher: 先端医学社
• [Book] 細胞工学 (2013)
  • Author(s): 黒田 雅士、阪上 浩
  • Total Pages: 5
  • Publisher: 学研メディカル秀潤社
• [Book] 救急・集中治療 (2012)
  • Author(s): 黒田 雅士, 他
  • Total Pages: 2
  • Publisher: 総合医学社