Elucidation of mechanisms by which exercise improves inflammation induced by type 2 diabetes

• Project/Area Number: 24591314
• 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 Tokyo
• Principal Investigator: FUJISHIRO Midori 東京大学, 医学部附属病院, 助教 (50420211)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 糖尿病

Outline of Final Research Achievements

To elucidate mechanisms by which exercise improves inflammation induced by type 2 diabetes, we chose the unique method which we have previously taken (J Biol Chem. 2011;286:20812-22, J Biol Chem. 2010;285:33018-27). The Myc-TEV-FLAG (MEF) tag cassette was generated by DNA synthesis and inserted into cloning sites in the mammalian expression vector pcDNA3. To create the N-terminally MEF-tagged MAP kinase constructs, each cDNA of three MAP kinases was inserted into pcDNA3-MEF. Then the coding portion of MEF-tagged MAPK was isolated from pcDNA3-MEF-MAPK, and the recombinant adenoviruses containing the cDNA coding for MEF-tagged MAPK were constructed. Recombinant adenoviruses expressing MAPK with the N-terminal MEF tag were used for adenoviral gene transfer to mouse muscles as previously described (Am J Physiol Endocrinol Metab. 2002;282:E1239-44). Subsequent purification of the complex containing MAPKs will clarify the key protein which binds to MAPKs in mouse muscles during exercise.

Research Products

• [Journal Article] Mosapride citrate improves nonalcoholic steatohepatitis with increased fecal lactic acid bacteria and plasma glucagon-like peptide-1 level in a rodent model. (2015)
  • Author(s): Hirofumi Okubo, Yusuke Nakatsu, Hideyuki Sakoda, Akifumi Kushiyama, Midori Fujishiro, Toshiaki Fukushima, Yasuka Matsunaga, Haruya Ohno, Masayasu Yoneda, Hideaki Kamata, Takanori Shinjo, Misaki Iwashita, Fusanori Nishimura, and Tomoichiro Asano
  • Journal Title: Am. J. Physiol. Gastrointest. Liver Physiol. Volume: 308 Issue: 2 Pages: 151-158
  • DOI: 10.1152/ajpgi.00198.2014
  • Peer Reviewed
• [Journal Article] Lung abscess without sepsis in a patient with diabetes with refractory episodes of spontaneous hypoglycemia: a case report and review of the literature. (2014)
  • Author(s): Toda G, Fujishiro M, Yamada T, Shojima N, Sakoda H, Suzuki R, Yamauchi T, Ueki K, Kadowaki T.
  • Journal Title: J Med Case Rep Volume: 8 Issue: 1 Pages: 51-51
  • DOI: 10.1186/1752-1947-8-51
  • Peer Reviewed
• [Journal Article] Detection of novel visible-light region absorbance peaks in the urine after alkalization in patients with alkaptonuria. (2014)
  • Author(s): Tokuhara Y, Shukuya K, Tanaka M, Mouri M, Ohkawa R, Fujishiro M, Takahashi T, Okubo S, Yokota H, Kurano M, Ikeda H, Yamaguchi S, Inagaki S, Ishige-Wada M, Usui H, Yatomi Y, Shimosawa T.
  • Journal Title: PLoS One Volume: 9 Issue: 1 Pages: e86606-e86606
  • DOI: 10.1371/journal.pone.0086606
  • Peer Reviewed
• [Journal Article] Par14 associates with IRS-1, thereby enhancing insulin-induced IRS-1 phosphorylation and metabolic actions. (2013)
  • Author(s): Zhang J, Nakatsu Y, Sinjo T, Guo Y, Sakoda H, Yamamotoya T, Otani Y, Okubo H, Kushiyama A, Fujishiro M, Fukushima T, Tsuchiya Y, Kamata H, Nishimura F, Katagiri H, Takahashi SI, Kurihara H, Uchida T, Asano T.
  • Journal Title: Ｊournal of Biological Chemistry Volume: 288 Issue: 28 Pages: 20692-20701
  • DOI: 10.1074/jbc.m113.485730
  • Peer Reviewed
• [Journal Article] Lactobacillus casei strain Shirota protects against non-alcoholic steatohepatitis development in a rodent model (2013)
  • Author(s): Okubo H, Sakoda H, Kushiyama A, Fujishiro M, Nakatsu Y, Fukushima T, Matsunaga Y, Kamata H, Asahara T, Yoshida Y, Chonan O, Iwashita M, Nishimura F, Asano T
  • Journal Title: American Journal Physiolgy-Gastrointestinal and Liver Physiogy Volume: 305 Issue: 12 Pages: 911-918
  • DOI: 10.1152/ajpgi.00225.2013
  • Peer Reviewed
• [Journal Article] Resistin-Like Molecule β Is Abundantly Expressed in Foam Cells and Is Involved in Atherosclerosis Development. (2013)
  • Author(s): Kushiyama A, Sakoda H, Oue N, Okubo M, Nakatsu Y, Ono H, Fukushima T, Kamata H, Nishimura F, Kikuchi T, Fujishiro M, Nishiyama K, Aburatani H, Kushiyama S, Iizuka M, Taki N, Encinas J, Sentani K, Ogonuki N, Ogura A, Kawazu S, Yasui W, Higashi Y, Kurihara H, Katagiri H, Asano T.
  • Journal Title: Arteriosclerosis, Thrombosis, and Vascular Biology Volume: 33 Issue: 8 Pages: 1986-1993
  • DOI: 10.1161/atvbaha.113.301546
  • Peer Reviewed / Open Access
• [Journal Article] Integrator complex plays anessential role inadipose differentiation (2013)
  • Author(s): Otani Y, Nakatsu Y, Sakoda H, Fukushima T, Fujishiro M, Kushiyama A, Okubo H, Tsuchiya Y, Ohno H, Takahashi S, Nishimura F, Kamata H, Katagiri H, Asano T.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 434 Issue: 2 Pages: 197-202
  • DOI: 10.1016/j.bbrc.2013.03.029
  • Peer Reviewed
• [Journal Article] Valsartan restores inflammatory response by macrophages in adipose and hepatic tissues of LPS-infused mice (2013)
  • Author(s): Iwashita M, Nakatsu Y, Sakoda H, Fujishiro M, Kushiyama A, Fukushima T, Kumamoto S, Shinjo T, Kamata H, Nishimura F, Asano T
  • Journal Title: Adipocyte Volume: 2(1) Issue: 1 Pages: 28-32
  • DOI: 10.4161/adip.21837
  • Peer Reviewed
• [Journal Article] Role of Pin1 in the pathogenesis of non-alcoholic steatohepatitis in a rodent model (2012)
  • Author(s): Nakatsu Y, Otani Y, Sakoda H, Zhang J, Guo Y, Okubo H, Kushiyama A, Fujishiro M, Kikuchi T, Fukushima T, Ohno H, Tsuchiya Y, Kamata H, Nagamachi A, Inaba T, Nishimura F, Katagiri H, Takahashi SI, Kurihara H, Uchida T, Asano T
  • Journal Title: J Biol Chem Volume: 287 Issue: 53 Pages: 44526-44535
  • DOI: 10.1074/jbc.m112.397133
  • Peer Reviewed
• [Presentation] Mosapride citrate improves non-alcoholic steatohepatitis with increased faecal lactic acid bacteria and plasma glucagon-like peptide-1 level in a rodent model. (2014)
  • Author(s): H. Okubo, M. Yoneda, H. Sakoda, A. Kushiyama, M. Fujishiro, Y. Nakatsu, T. Fukushima1, Y. Matsunaga, H. Kamata, M. Iwashita, F. Nishimura, A. Tomoichiro
  • Organizer: 50th EASD Annual Meeting
  • Place of Presentation: Vienna
  • Year and Date: 2014-09-15 – 2014-09-19
• [Presentation] The Role of Linear Ubiquitin Chain Assembly Complex (LUBAC) and its Components in Insulin Signal Transduction. (2014)
  • Author(s): Yamamotoya T, Sakoda H, Fujishiro M, Kaneko S, Yamazaki H, Kikuchi T, Kushiyama A, Asano T
  • Organizer: 74th Scientific Sessions of the American Diabetes Association
  • Place of Presentation: San Francisco
  • Year and Date: 2014-06-13 – 2014-06-17
• [Presentation] キサンチンオキシターゼ阻害剤FebuxostatによるNASH改善作用の検討 (2014)
  • Author(s): 藤城緑, 迫田秀之, 山本屋武, 中津祐介, 福嶋俊明, 松永泰花, 浅野知一郎, 櫛山暁史, 西村英紀
  • Organizer: 第57回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] 非アルコール性脂肪肝炎発症におけるLUBAC形成障害の役割 (2014)
  • Author(s): 松永泰花, 中津祐介, 鎌田英明, 福嶋俊明, 岩下未咲, 新城尊徳, 浅野知一郎, 菊池貴子, 藤城緑
  • Organizer: 第57回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] LUBAC(linear ubiquitin chain assembly complex)のインスリンシグナル伝達系における役割の検討 (2014)
  • Author(s): 山本屋武, 迫田秀之, 藤城緑, 山崎広貴, 菊池貴子, 櫛山暁史, 浅野知一郎
  • Organizer: 第57回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] マクロファージとの共培養系においてValsartanが脂肪細胞の遺伝子発現に与える影響 (2012)
  • Author(s): 藤城 緑，郭 榮，張 君，中津 祐介，櫛山 暁史，福嶋 俊明， 鎌田 英明，栗原 裕基，内田 隆史，迫田 秀之，浅野 知一郎
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: パシフィコ横浜
• [Presentation] 非アルコール性脂肪肝炎(NASH)に対するクエン酸モサプリド投与の効果
  • Author(s): 藤城緑、中津祐介、大谷裕一郎、大久保博史、岩下未咲、西村英紀、迫田秀之、櫛山暁史、菊池貴子、浅野知一郎
  • Organizer: 第 56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本
• [Presentation] 糖尿病外来における消化器症状調査結果
  • Author(s): 山崎 広貴，藤城 緑，金子 直，纐纈 優子，山本屋 武，迫田 秀之，植木 浩二郎，門脇 孝
  • Organizer: 第 56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本