Twenty-four hours physical inactivity induce insulin resistance in the muscle.

• Project/Area Number: 18K11029
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Juntendo University
• Principal Investigator: Kakehi Saori 順天堂大学, 医学(系)研究科(研究院), 特任助教 (00450560)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 骨格筋 / インスリン感受性 / 不活動 / 骨格筋細胞内脂質 / Lipin1 / インスリン抵抗性 / 筋量

Outline of Final Research Achievements

Physical inactivity (PI) has been shown to impair muscle insulin sensitivity (M-IS); however, its mechanisms have not been elucidated yet. To elucidate the mechanism by which inactivity induces skeletal muscle insulin resistance, we immobilized the unilateral lower limb of mice for 24 hours and assessed soleus and plantaris as a model of inactivity. However, the mechanism of this phenomenon was different among muscle fiber types. The mechanism of this phenomenon was different depending on the muscle fiber type. In soleus, which is predominantly slow-twitch muscle, there was intracellular DAG accumulation due to changes in Lipin1 expression and activity, while in plantaris, which is predominantly fast-twitch muscle, it was suggested that PTP1B may reduce insulin signaling.
These results indicate that the mechanism by which physical inactivity reduces insulin sensitivity differs among muscle fiber types.

Academic Significance and Societal Importance of the Research Achievements

日本における糖尿病患者の平均BMIは23 kg/m2と正常レベルであることを考えると、日本人などの東洋人の糖尿病や動脈硬化症の病態を考える上で、非肥満者に認められるインスリン抵抗性の病態生理学の確立が必要であると考えられる。その点において不活動のインスリン抵抗性惹起メカニズムが明らかになることは、これからの健康寿命増進や医療経済への貢献は計り知れないものであると思われる。

Research Products

• [Journal Article] Author Correction: Both higher fitness level and higher current physical activity level may be required for intramyocellular lipid accumulation in non-athlete men (2021)
  • Author(s): Yamasaki N, Tamura Y, Takeno K, Kakehi S, Someya Y, Funayama T, Furukawa Y, Kaga H, Suzuki R, Sugimoto D, Kadowaki S, Sato M, Nakagata T, Nishitani-Yokoyama M, Shimada K, Daida H, Aoki S, Satoh H, Kawamori R, Watada H.
  • Journal Title: Sci Rep Volume: 25 Issue: 1 Pages: 7304-7304
  • DOI: 10.1038/s41598-021-86892-x
  • Peer Reviewed / Open Access
• [Journal Article] A chronic high-fat diet exacerbates contractile dysfunction with impaired intracellular Ca 2+ release capacity in the skeletal muscle of aged mice (2020)
  • Author(s): Eshima H, Tamura Y, Kakehi S, Kakigi R, Hashimoto R, Funai K, Kawamori R, Watada H.
  • Journal Title: J Appl Physiol (1985). Volume: 128 Issue: 5 Pages: 1153-1162
  • DOI: 10.1152/japplphysiol.00530.2019
  • Peer Reviewed
• [Journal Article] Shape of the glucose response curve during an oral glucose tolerance test is associated with insulin clearance and muscle insulin sensitivity in healthy non-obese men. (2020)
  • Author(s): Kaga H, Tamura Y, Takeno K, Kakehi S, Someya Y, Funayama T, Furukawa Y, Suzuki R, Sugimoto D, Kadowaki S, Nishitani-Yokoyama M, Shimada K, Daida H, Aoki S, Giacca A, Sato H, Kawamori R, Watada H.
  • Journal Title: J Diabetes Investig. Volume: . Issue: 4 Pages: 874-877
  • DOI: 10.1111/jdi.13227
  • Peer Reviewed / Open Access
• [Journal Article] Effects of blood flow restriction on muscle size and gene expression in muscle during immobilization: A pilot study (2020)
  • Author(s): Kakehi S, Tamura Y, Kubota A, Takeno K, Kawaguchi M, Sakuraba K, Kawamori R, Watada H.
  • Journal Title: Physiol Rep. Volume: 8 Issue: 14
  • DOI: 10.14814/phy2.14516
  • Peer Reviewed / Open Access
• [Journal Article] Characteristics associated with elevated 1-h plasma glucose levels during a 75-g oral glucose tolerance test in non-obese Japanese men. (2020)
  • Author(s): Sato M, Tamura Y, Someya Y, Takeno K, Kaga H, Kadowaki S, Sugimoto D, Kakehi S, Funayama T, Furukawa Y, Suzuki R, Nakagata T, Nishitani-Yokoyama M, Shimada K, Daida H, Aoki S, Sato H, Kawamori R, Watada H.
  • Journal Title: J Diabetes Investig Volume: . Issue: 6 Pages: 1520-1523
  • DOI: 10.1111/jdi.13245
  • Peer Reviewed / Open Access
• [Journal Article] Decreased Muscle Strength of Knee Flexors is Associated with Impaired Muscle Insulin Sensitivity in Non-Diabetic Middle-Aged Japanese Male Subjects (2020)
  • Author(s): Someya Y, Tamura Y, Takeno K, Kakehi S, Funayama T, Furukawa Y, Eshima H, Watanabe K, Kurihara T, Yanagiya T, Kaga H, Suzuki R, Sugimoto D, Kadowaki S, Kawamori R, Watada H.
  • Journal Title: Diabetes Ther. Volume: 11 Issue: 10 Pages: 2401-2410
  • DOI: 10.1007/s13300-020-00895-x
  • Peer Reviewed / Open Access
• [Journal Article] Endurance runners with intramyocellular lipid accumulation and high insulin sensitivity have enhanced expression of genes related to lipid metabolism in muscle (2020)
  • Author(s): Kakehi Saori、Tamura Yoshifumi、Takeno Kageumi、Ikeda Shin-ichi、Ogura Yuji、Saga Norio、Miyatsuka Takeshi、Naito Hisashi、Kawamori Ryuzo、Watada Hirotaka
  • Journal Title: Journal of Clinical Medicine Volume: 9 Issue: 12 Pages: 1
  • DOI: 10.3390/jcm9123951
  • URL: https://localhost/en/publications/18ea17d9-c471-4dee-bae3-5a6e8c72c9aa
  • Peer Reviewed / Open Access
• [Journal Article] Both higher fitness level and higher current physical activity level may be required for intramyocellular lipid accumulation in non-athlete men. (2020)
  • Author(s): Yamasaki N, Tamura Y, Takeno K, Kakehi S, Someya Y, Funayama T, Furukawa Y, Kaga H, Suzuki R, Sugimoto D, Kadowaki S, Sato M, Nakagata T, Nishitani-Yokoyama M, Shimada K, Daida H, Aoki S, Sato H, Kawamori R, Watada H.
  • Journal Title: Sci Rep. Volume: 10 Issue: 1 Pages: 4102-4102
  • DOI: 10.1038/s41598-020-61080-5
  • Peer Reviewed / Open Access
• [Journal Article] Clinical Features of Nonobese, Apparently Healthy, Japanese Men With Reduced Adipose Tissue Insulin Sensitivity. (2019)
  • Author(s): Sugimoto D, Tamura Y, Takeno K, Kaga H, Someya Y, Kakehi S, Funayama T, Furukawa Y, Suzuki R, Kadowaki S, Nishitani-Yokoyama M, Shimada K, Daida H, Aoki S, Kanazawa A, Kawamori R, Watada H.
  • Journal Title: J Clin Endocrinol Metab Volume: 104 Issue: 6 Pages: 2325-2333
  • DOI: 10.1210/jc.2018-02190
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Three days of a eucaloric, low-carbohydrate/high-fat diet increases insulin clearance in healthy non-obese Japanese men. (2019)
  • Author(s): Suzuki R, Tamura Y, Takeno K, Kakehi S, Funayama T, Furukawa Y, Kaga H, Sugimoto D, Kadowaki S, Someya Y, Kanazawa A, Kawamori R, Watada H.
  • Journal Title: Sci Rep. Volume: 9 Issue: 1 Pages: 3857-3857
  • DOI: 10.1038/s41598-019-40498-6
  • Peer Reviewed / Open Access
• [Journal Article] Fatty Liver Has Stronger Association With Insulin Resistance Than Visceral Fat Accumulation in Nonobese Japanese Men. (2019)
  • Author(s): Kadowaki S, Tamura Y, Someya Y, Takeno K, Kaga H, Sugimoto D, Kakehi S, Funayama T, Furukawa Y, Suzuki R, Nishitani-Yokoyama M, Shimada K, Daida H, Aoki S, Kanazawa A, Kawamori R, Watada H.
  • Journal Title: J Endocr Soc. Volume: 3 Issue: 7 Pages: 1409-1416
  • DOI: 10.1210/js.2019-00052
  • Peer Reviewed / Open Access
• [Journal Article] Higher C-Peptide Level During Glucose Clamp Is Associated With Muscle Insulin Resistance in Nonobese Japanese Men. (2019)
  • Author(s): Kaga H, Tamura Y, Takeno K, Kakehi S, Someya Y, Funayama T, Furukawa Y, Suzuki R, Sugimoto D, Kadowaki S, Nishitani-Yokoyama M, Shimada K, Daida H, Aoki S, Giacca A, Kanazawa A, Kawamori R, Watada H.
  • Journal Title: J Endocr Soc Volume: 3 Issue: 10 Pages: 1847-1857
  • DOI: 10.1210/js.2019-00167
  • Peer Reviewed / Open Access
• [Journal Article] Dysfunction of muscle contraction with impaired intracellular Ca2+ handling in skeletal muscle and the effect of exercise training in male db/db mice (2019)
  • Author(s): Eshima Hiroaki、Tamura Yoshifumi、Kakehi Saori、Nakamura Kyoko、Kurebayashi Nagomi、Murayama Takashi、Kakigi Ryo、Sakurai Takashi、Kawamori Ryuzo、Watada Hirotaka
  • Journal Title: Journal of Applied Physiology Volume: 126 Issue: 1 Pages: 170-182
  • DOI: 10.1152/japplphysiol.00048.2018
  • Peer Reviewed / Open Access / Int'l Joint Research