Investigation of the role of advanced glycation end products in musculoskeletal vascular disease and exploration of novel therapeutic mechanisms induced by exercise

• Project/Area Number: 18K17697
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 59010:Rehabilitation science-related
• Research Institution: Okayama Healthcare Professional University (2020-2022); Osaka University of Human Sciences (2018-2019)
• Principal Investigator: Tanaka Masayuki 岡山医療専門職大学, 健康科学部 理学療法学科, 助教 (10780497)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 骨格筋 / 血管障害 / 運動 / 終末糖化産物 / 毛細血管 / 糖化ストレス

Outline of Final Research Achievements

The purpose of this study was to elucidate 1) the effects of glycation stress on the capillary network of skeletal muscle and 2) the effects of exercise intervention on muscle capillary rarefaction caused by glycation stress. Glycation stress mainly induced capillary rarefaction in fast-twitch skeletal muscle. In addition, glycation stress attenuated the effect of exercise intervention on capillary growth in fast-twitch skeletal muscle. This effect involved the fact that glycation stress attenuated the increase in angiogenic factors induced by exercise. These results suggest that glycation stress impairs muscle capillary capillary architecture and its adaptability to exercise.

Academic Significance and Societal Importance of the Research Achievements

骨格筋内の毛細血管は筋細胞に酸素や糖など筋の成長や代謝活動に必要な物質を送達する重要な役割を担っており、筋の量や持久力、糖代謝能などを規定している。加齢や慢性疾患により身体は糖化ストレスに曝されるが、これまで糖化ストレスが骨格筋内の血管構築に及ぼす影響は不明であった。本研究では糖化ストレスが骨格筋の毛細血管構築を障害すること、および運動による筋内の毛細血管新生を減弱することが明らかとなり、骨格筋内の毛細血管の健康を維持するには糖化ストレスを制御することが重要であることを示唆できた。本研究成果は、骨格筋の健康維持を目的とした糖化ストレス制御に焦点を当てた介入戦略の構築に有益な情報となると考える。

Research Products

• [Journal Article] Brazilian propolis intake decreases body fat mass and oxidative stress in community-dwelling elderly females: A randomized placebo-controlled trial. (2023)
  • Author(s): Kanazashi M, Iida T, Nakanishi R, Tanaka M, Ikeda H, Takamiya N, Maeshige N, Kondo H, Nishigami T, Harada T, Fujino H.
  • Journal Title: Nutrients Volume: 15 Issue: 2 Pages: 364-364
  • DOI: 10.3390/nu15020364
  • Peer Reviewed / Open Access
• [Journal Article] Impacts of astaxanthin supplementation on walking capacity by reducing oxidative stress in nursing home residents. (2022)
  • Author(s): Nakanishi R, Kanazashi M, Tanaka M, Tanaka M, Fujino H.
  • Journal Title: Int J Environ Res Public Health Volume: 19 Issue: 20 Pages: 13492-13492
  • DOI: 10.3390/ijerph192013492
  • Peer Reviewed / Open Access
• [Journal Article] Effect of Stretching on Periarticular Muscles in Ankle and Foot (2022)
  • Author(s): 前重 伯壮、吉川 義之、植村 弥希子、平沢 良和、田中 雅侑、河辺 信秀、藤井 美樹、寺師 浩人、藤野 英己
  • Journal Title: Journal of Japanese Society for Foot Care and Podiatric Medicine Volume: 3 Issue: 2 Pages: 71-75
  • DOI: 10.34466/jjsfcpm.3.2_71
  • ISSN: 2435-4775, 2435-4783
  • Open Access
• [Journal Article] Prediction of callus and ulcer development in patients with diabetic peripheral neuropathy by isosceles triangle-forming tuning fork (2022)
  • Author(s): Yoshikawa Y, Maeshige N, Uemura M, Tanaka M, Kawabe N, Yamaguchi A, Fujino H, Terashi H
  • Journal Title: SAGE Open Med Volume: 15
  • DOI: 10.1177/20503121221085097
  • Peer Reviewed
• [Journal Article] Time course of capillary regression and an expression balance between vascular endothelial growth factor-A and thrombospondin-1 in the soleus muscle of hindlimb unloaded rats (2022)
  • Author(s): Tanaka M, Kanazashi M, Kondo H, Fujino H.
  • Journal Title: Muscle Nerve Volume: 63 Issue: 3 Pages: 350-360
  • DOI: 10.1002/mus.27478
  • Peer Reviewed
• [Journal Article] Relationship between the cleaning frequency and healing time of pressure ulcers in elderly receiving home care: An observational pilot study (2022)
  • Author(s): Yoshikawa Yoshiyuki、Maeshige Noriaki、Tanaka Masayuki、Uemura Mikiko、Hiramatsu Terutaka、Fujino Hidemi、Sugimoto Masaharu、Terashi Hiroto
  • Journal Title: Journal of Wound Care Volume: in press
  • Peer Reviewed
• [Journal Article] Mild hyperbaric oxygen exposure attenuates rarefaction of capillary vessels in streptozotocin-induced diabetic soleus muscle in rats (2021)
  • Author(s): TANAKA Masayuki、KANAZASHI Miho、MATSUMOTO Tomohiro、KONDO Hiroyo、ISHIHARA Akihiko、FUJINO Hidemi
  • Journal Title: Biomedical Research Volume: 42 Issue: 1 Pages: 1-11
  • DOI: 10.2220/biomedres.42.1
  • NAID: 130007983457
  • ISSN: 0388-6107, 1880-313X
  • Year and Date: 2021-02-10
  • Peer Reviewed / Open Access
• [Journal Article] Licorice flavonoid oil supplementation promotes a reduction of visceral fat in exercised rats (2021)
  • Author(s): TANAKA Masayuki、KANAZASHI Miho、KONDO Hiroyo、ISHIHARA Akihiko、FUJINO Hidemi
  • Journal Title: The Journal of Sports Medicine and Physical Fitness Volume: 61 Issue: 3 Pages: 480-488
  • DOI: 10.23736/s0022-4707.20.11260-x
  • Peer Reviewed / Open Access
• [Journal Article] Effects of reloading after chronic neuromuscular inactivity on the three-dimensional capillary architecture in rat soleus muscle (2020)
  • Author(s): Kanazashi Miho、Tanaka Masayuki、Maezawa Toshiyuki、Fujino Hidemi
  • Journal Title: Acta Histochemica Volume: 122 Issue: 7 Pages: 151617-151617
  • DOI: 10.1016/j.acthis.2020.151617
  • Peer Reviewed
• [Journal Article] Effects of astaxanthin supplementation and electrical stimulation on muscle atrophy and decreased oxidative capacity in soleus muscle during hindlimb unloading in rats (2019)
  • Author(s): Kanazashi M, Tanaka M, Nakanishi R, Maeshige N, Fujino H.
  • Journal Title: J Physiol Sci Volume: 69 Issue: 5 Pages: 757-767
  • DOI: 10.1007/s12576-019-00692-7
  • NAID: 40022006466
  • Peer Reviewed / Open Access
• [Journal Article] Transcutaneous carbon dioxide attenuates impaired oxidative capacity in skeletal muscle in hyperglycemia model (2019)
  • Author(s): Matsumoto T.、Tanaka M.、Nakanishi R.、Takuwa M.、Hirabayashi T.、Ono K.、Ikeji T.、Maeshige N.、Sakai Y.、Akisue T.、Kondo H.、Ishihara A.、Fujino H.
  • Journal Title: General physiology and biophysics Volume: 38 Issue: 03 Pages: 237-244
  • DOI: 10.4149/gpb_2018048
  • Peer Reviewed / Open Access
• [Journal Article] Application of transcutaneous carbon dioxide improves capillary regression of skeletal muscle in hyperglycemia (2019)
  • Author(s): Matsumoto T, Tanaka M, Ikeji T, Maeshige N, Sakai Y, Akisue T, Kondo H, Ishihara A, Fujino H
  • Journal Title: J Physiol Sci Volume: 69 Issue: 2 Pages: 223-233
  • DOI: 10.1007/s12576-018-0648-y
  • NAID: 40021819003
  • Peer Reviewed
• [Journal Article] Protective effects of Brazilian propolis supplementation on capillary regression in the soleus muscle of hindlimb-unloaded rats (2018)
  • Author(s): Tanaka Masayuki、Kanazashi Miho、Maeshige Noriaki、Kondo Hiroyo、Ishihara Akihiko、Fujino Hidemi
  • Journal Title: The Journal of Physiological Sciences Volume: 69 Issue: 2 Pages: 223-233
  • DOI: 10.1007/s12576-018-0639-z
  • NAID: 40021818923
  • Peer Reviewed / Open Access
• [Journal Article] モノクロタリン誘発性肺高血圧症ラットのヒラメ筋におけるミトコンドリア機能障害と毛細血管退行に対する中周波電気刺激の介入効果 (2018)
  • Author(s): 田中雅侑，前重伯壮，金指美帆，中西亮介，藤野英己
  • Journal Title: 物理療法科学 Volume: 25 Pages: 42-49
  • NAID: 40021724120
  • Peer Reviewed
• [Journal Article] 心不全による骨格筋の毛細血管退行に対するレーザー照射の治療効果 (2018)
  • Author(s): 上野瑞季，田中雅侑，平山佑介，金指美帆，松本智博，前重伯壮，藤野英己
  • Journal Title: 物理療法科学 Volume: 25 Pages: 50-56
  • NAID: 40021724149
  • Peer Reviewed
• [Presentation] 電気刺激が骨格筋肥大と血管新生の分子シグナルに及ぼす効果は糖化ストレスにより減弱する (2023)
  • Author(s): 田中雅侑, 金指美帆, 近藤浩代, 藤野英己.
  • Organizer: 日本物理療法合同学術大会2023
• [Presentation] 糖化ストレスはラット前脛骨筋におけるレジスタンス運動誘発性の筋タンパク質合成を減弱する (2022)
  • Author(s): 田中雅侑, 金指美帆, 近藤浩代, 藤野英己.
  • Organizer: 第27回日本基礎理学療法学会学術大会
• [Presentation] 高脂肪食摂取に起因する筋内脂肪蓄積に対する交流磁場刺激の予防効果 (2022)
  • Author(s): 中西亮介, 田中雅侑, 藤野英己.
  • Organizer: 第87回日本温泉気候物理医学会総会・学術大会
• [Presentation] 終末糖化産物前駆体の摂取はレジスタンス運動による筋タンパク質合成を減弱させる (2021)
  • Author(s): 田中雅侑, 金指美帆, 近藤浩代, 藤野英己.
  • Organizer: 第76回日本体力医学会大会
• [Presentation] 高脂肪食由来の筋内脂肪蓄積に対する交流磁気刺激の効果 (2021)
  • Author(s): 中西亮介, Badur un Nisa, 志水沙耶果, 田中雅侑, 平林卓己, 田中稔, 藤野英己.
  • Organizer: 第76回日本体力医学会大会
• [Presentation] 後肢非荷重期間がラットヒラメ筋における毛細血管と血管新生及び退行因子の発現動態に及ぼす経時的変化 (2020)
  • Author(s): 田中雅侑，金指美帆，藤野英己．
  • Organizer: 第75回日本体力医学会（web開催）
• [Presentation] 後肢非荷重期間におけるプラゾシンの投与がラットヒラメ筋に与える影響 (2020)
  • Author(s): 金指美帆，田中雅侑，奥村将太，佐竹弘吉，津森登志子．
  • Organizer: 第75回日本体力医学会（web開催）
• [Presentation] 軽度高気圧高酸素曝露が糖尿病による速筋の筋量及び代謝機能障害に及ぼす影響 (2020)
  • Author(s): 天野英紀，藤澤秋子，Zeidan Hala，田中雅侑，近藤浩代，石原昭彦，藤野英己．
  • Organizer: 第75回日本体力医学会（web開催）
• [Presentation] Combinational effects of electrical stimulation and antioxidant astaxanthin supplementation on muscle atrophy and impaired oxidative capacity within unloaded skeletal muscle (2019)
  • Author(s): Miho Kanazashi, Masayuki Tanaka, Noriaki Maeshige, Hidemi Fujino
  • Organizer: World Confederation for Physical Therapy Conference, (Geneva
• [Presentation] 高血糖曝露に伴う骨格筋毛細血管退行に対する高気圧高酸素療法の介入効果 (2019)
  • Author(s): 田中雅侑， 金指美帆，中西亮介，近藤浩代，藤野英己
  • Organizer: 第74回日本体力医学会大会（茨城県）
• [Presentation] 地域高齢者の運動器症候群に対するプロポリス摂取による酸化ストレスの抑制を介した予防効果 (2019)
  • Author(s): 金指美帆，飯田忠行，池田ひろみ，髙宮尚美，原田俊英，中西亮介，田中雅侑，藤野英己
  • Organizer: 第74回日本体力医学会大会（茨城県）
• [Presentation] 高脂質食誘導性肥満の骨格筋における筋損傷治癒遅延に対するパルスモード超音波の効果 (2018)
  • Author(s): 松本智博，田中雅侑，池冶拓也，前重伯壮，藤野英己
  • Organizer: 第26回日本物理療法学会学術大会