アスリートパラドックスの全容解明と臨床応用の検討

2015 Fiscal Year Annual Research Report

• Project/Area Number: 15H03097
• Research Institution: Juntendo University
• Principal Investigator: 河盛 隆造 順天堂大学, 医学(系)研究科(研究院), 教授 (00116021)
• Co-Investigator(Kenkyū-buntansha): 筧 佐織 順天堂大学, 医学(系)研究科(研究院), 特任助教 (00450560) ; 田村 好史 順天堂大学, 医学部, 准教授 (80420834)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 骨格筋 / 骨格筋細胞内脂質 / アスリートパラドックス / インスリン感受性

Outline of Annual Research Achievements

長距離ランナーでは骨格筋細胞内脂質が多いにも関わらずインスリン感受性が高いことが明らかとなってきており、さらに肥満者などでも強度の比較的強い有酸素運動することにより同様の現象が生じうるということが明らかとなってきている。これら一連の逆説的な事象は「アスリートパラドックス」と呼ばれている。本研究では、アスリートパラドックスのメカニズム解明のため、本学陸上部の長距離ランナーから骨格筋サンプルを採取し、マイクロアレイ解析により新規候補遺伝子抽出を行った。対象は、長距離ランナーで特に骨格筋細胞内脂質が多く蓄積しているが、インスリン感受性が高く保たれている者5名とBMIをマッチさせた健常者7名とした。長距離ランナーでは、骨格筋細胞内脂質は健常者の4倍と極めて高かったが、インスリン感受性は両群とも同等で正常であった。骨格筋における遺伝子発現解析をマイクロアレイによる解析とその後のC2C12マウス筋管細胞を用いたin vitroでのスクリーニングによって、アスリートパラドックスのメカニズムに関わっている可能性が高い候補遺伝子を3遺伝子まで絞り込んだ。次年度は抽出された候補遺伝子に対してさらなるメカニズムの解明を行う。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

当初の研究計画に沿って順調に研究を行えている。

Strategy for Future Research Activity

今後も共同研究者と緊密に連携を取りながら研究を進める。

Research Products

• [Journal Article] Increased intramyocellular lipid/impaired insulin sensitivity is associated with altered lipid metabolic genes in muscle of high responders to a high-fat diet. (2016)
  • Author(s): Kakehi S, Tamura Y, Takeno K, Sakurai Y, Kawaguchi M, Watanabe T, Funayama T, Sato F, Ikeda S, Kanazawa A, Fujitani Y, Kawamori R, Watada H
  • Journal Title: Am J Physiol Endocrinol Metab. Volume: 310 Pages: 32-40
  • DOI: 10.1152/ajpendo.00220.2015.
  • Peer Reviewed
• [Journal Article] Efficacy and safety of 40 mg or 60 mg duloxetine in Japanese adults with diabetic neuropathic pain: Results from a randomized, 52-week, open-label study. (2016)
  • Author(s): Yasuda H, Hotta N, Kasuga M, Kashiwagi A, Kawamori R, Yamada T, Baba Y, Alev L, Nakajo K.
  • Journal Title: J Diabetes Investig Volume: 7 Pages: 100-108
  • DOI: 10.1111/jdi.12361.
  • Peer Reviewed
• [Journal Article] Dynamic prediction model and risk assessment chart for cardiovascular disease based on on-treatment blood pressure and baseline risk factors. (2016)
  • Author(s): Teramukai S, Okuda Y, Miyazaki S, Kawamori R, Shirayama M, Teramoto T.
  • Journal Title: Hypertens Res Volume: 39 Pages: 113-8
  • DOI: 10.1038/hr.2015.120.
  • Peer Reviewed
• [Journal Article] Does the treatment of type 2 diabetes mellitus with the DPP -4 inhibitor vildagliptin reduce HbA1c to a greater extent in Japanese patients than in Caucasian patients? (2016)
  • Author(s): James E Foley, Vaishali Bhosekar, Kawamori R.
  • Journal Title: Vascular Health and Risk Management Volume: 12 Pages: 9-12
  • DOI: 10.2147/VHRM.S96971.
  • Peer Reviewed
• [Journal Article] Effects of Pioglitazone for Secondary Stroke Prevention in Patients with Impaired Glucose Tolerance and Newly Diagnosed Diabetes: The J-SPIRIT Study (2015)
  • Author(s): Tanaka R, Yamashiro K, Okuma Y, Shimura H, Nakamura S, Ueno Y, Tanaka Y, Miyamoto N, Tomizawa Y, Nakahara T, Furukawa Y, Watada H, Kawamori R, Hattori N, Urabe T.
  • Journal Title: J Atheroscler Thromb Volume: 22 Pages: 1305-16
  • DOI: 10.5551/jat.30007
  • Peer Reviewed
• [Journal Article] Replication Study in a Japanese Population to Evaluate the Association between 10 SNP Loci, Identified in European Genome-Wide Association Studies, and Type 2 Diabetes. (2015)
  • Author(s): Matsuba R, Sakai K, Imamura M, Tanaka Y, Iwata M, Hirose H, Kaku K, Maegawa H, Watada H, Tobe K, Kashiwagi A, Kawamori R, Maeda S.
  • Journal Title: PLoS One Volume: 10 Pages: e0126363
  • DOI: 10.1371/journal.pone.0126363.
  • Peer Reviewed
• [Journal Article] Evaluation of myocardial triglyceride accumulation assessed on 1H-magnetic resonance spectroscopy in apparently healthy Japanese subjects. (2015)
  • Author(s): Sai E, Shimada K, Yokoyama T, Sato S, Nishizaki Y, Miyazaki T, Hiki M, Tamura Y, Aoki S, Watada H, Kawamori R,Daida H.
  • Journal Title: Journal of Diabetes Investigation Volume: 6 Pages: 164-172
  • DOI: 10.2169/internalmedicine.54.3024.
  • Peer Reviewed
• [Journal Article] Effects of sitagliptin on ectopic fat contents and glucose metabolism in type 2 diabetic patients with fatty liver: A pilot study. (2015)
  • Author(s): Watanabe T, Tamura Y, Kakehi S, Funayama T, Takeno K, Kawaguchi M, Yamamoto L, Sato F, Ikeda S, Taka H, Fujimura T, Fujitani Y, Kawamori R,Watada H.
  • Journal Title: Journal of Diabetes Investigation Volume: 6 Pages: 164-172
  • DOI: 10.1111/jdi.12262
  • Peer Reviewed
• [Journal Article] Four-year evolution of insulin regimens, glycaemic control, hypoglycaemia and body weight after starting insulin therapy in type 2 diabetes across three continents. (2015)
  • Author(s): Home PD, Dain M-P, Freemantle N, Kawamori R, Pfohl M, Brette S, Pilorget V, Scherbaum WA, Vespasiani G, Vincent M, Balkau B.
  • Journal Title: Diabetes Res Clin Pract Volume: 108 Pages: 350-9
  • DOI: 10.1016/j.diabres.2015.01.030.
  • Peer Reviewed
• [Journal Article] The factors that affect exercise therapy for patients with type 2 diabetes in Japan: a nationwide survey. (2015)
  • Author(s): Arakawa S, Watanabe T, Sone H, Tamura Y, Kobayashi M, Kawamori R, Atsumi Y, Oshida Y, Tanaka S, Suzuki S, Makita S, Ohsawa I, Sato Yuzo.
  • Journal Title: Diabetol Int Volume: 6 Pages: 19-25
  • Peer Reviewed
• [Journal Article] Lipid and blood pressure control for the prevention of cardiovascular disease in hypertensive patients: a subanalysis of the OMEGA study. (2015)
  • Author(s): Teramoto T, Kawamori R, Miyazaki S, Teramukai S, Sato Y, Okuda Y, Shirayama M.
  • Journal Title: J Atheroscler Thromb Volume: 22 Pages: 62-75
  • DOI: 10.5551/jat.25304
  • Peer Reviewed
• [Presentation] 高脂肪・不活動による骨格筋インスリン抵抗性惹起メカニズム (2015)
  • Author(s): 筧 佐織、田村 好史、池田 真一、加賀 直子、河盛 隆造、綿田 裕孝
  • Organizer: 分子糖尿病学シンポジウム
  • Place of Presentation: 東京、千代田区、丸ビルホール&コンファレンススクエア
  • Year and Date: 2015-12-05
• [Presentation] 24時間の脚ギプス固定は、骨格筋細胞内のジアシルグリセロールを増加させ、インスリン抵抗性を惹起する (2015)
  • Author(s): 筧 佐織、田村 好史、池田 真一、河盛 隆造、綿田 裕孝
  • Organizer: 第70回体力医学会大会
  • Place of Presentation: 和歌山、和歌山市、和歌山県民文化会館
  • Year and Date: 2015-09-18 – 2015-09-20
• [Presentation] Intramyocellular lipid accumulation after high-fat diet is associated with the gene expression involved in lipid metabolism in skeletal muscle of non-obese men (2015)
  • Author(s): Kakehi S, Tamura Y, Takeno K, Sakurai Y, Kawaguchi M, Watanabe T, Funayama T, Sato F, Ikeda S, Kanazawa A, Fujitani Y, Kawamori R, Watada H
  • Organizer: 2nd Congress, International Academy of Sportology.
  • Place of Presentation: 東京、文京区、順天堂大学
  • Year and Date: 2015-09-12
• [Presentation] Physical inactivity and high fat diet synergistically enhance the accumulation of intramyocellular diacylglycerol and induce insulin resistance in murine soleus muscle (2015)
  • Author(s): Kakehi S, Tamura Y, Kawamori R, Watada H
  • Organizer: Cell Symposia: Exercise Metabolism.
  • Place of Presentation: アムステルダム、オランダ
  • Year and Date: 2015-07-12 – 2015-07-14
• [Presentation] 「Potential usefulness of intrahepatic lipid accumulation and liver function tests to identify insulin resistance phenotype in non-obese type 2 diabetes.」 (2015)
  • Author(s): Y. Furukawa, Y. Tamura, K. Takeno, T. Funayama, R. Suzuki, H. Kaga, T. Watanabe, Y. Someya, Y. Fujitani, R. Kawamori, H. Watada
  • Organizer: American Diabetes Association 75th scientific sessions
  • Place of Presentation: ボストン、アメリカ合衆国
  • Year and Date: 2015-06-05 – 2015-06-09
• [Presentation] Mechanisums of insulin resistance after 24hours physical inactivity in murine soleus muscle (2015)
  • Author(s): Kakehi S, Tamura Y, Ikeda S, Kawamori R, Watada H
  • Organizer: 62nd Annual Meeting of American College of Sports Medicine.
  • Place of Presentation: サンディエゴ、アメリカ合衆国
  • Year and Date: 2015-05-26 – 2015-05-30