Physical inactivity induces insulin resistance in plantaris muscle through protein tyrosine phosphatase 1B activation in mice
Inactivity causes insulin resistance in skeletal muscle and exacerbates various lifestyle-related diseases. We previously found that 24-h hindlimb cast immobilization (HCI) of the predominantly slow-twitch soleus muscle increased intramyocellular diacylglycerol (IMDG) and insulin resistance by activ...
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| Format: | Article |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2023.1198390/full |
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| author | Saori Kakehi Saori Kakehi Yoshifumi Tamura Yoshifumi Tamura Shin-ichi Ikeda Shin-ichi Ikeda Naoko Kaga Hikari Taka Yuya Nishida Ryuzo Kawamori Ryuzo Kawamori Hirotaka Watada Hirotaka Watada |
| author_facet | Saori Kakehi Saori Kakehi Yoshifumi Tamura Yoshifumi Tamura Shin-ichi Ikeda Shin-ichi Ikeda Naoko Kaga Hikari Taka Yuya Nishida Ryuzo Kawamori Ryuzo Kawamori Hirotaka Watada Hirotaka Watada |
| author_sort | Saori Kakehi |
| collection | DOAJ |
| description | Inactivity causes insulin resistance in skeletal muscle and exacerbates various lifestyle-related diseases. We previously found that 24-h hindlimb cast immobilization (HCI) of the predominantly slow-twitch soleus muscle increased intramyocellular diacylglycerol (IMDG) and insulin resistance by activation of lipin1, and HCI after a high-fat diet (HFD) further aggravated insulin resistance. Here, we investigated the effects of HCI on the fast-twitch–predominant plantaris muscle. HCI reduced the insulin sensitivity of plantaris muscle by approximately 30%, and HCI following HFD dramatically reduced insulin sensitivity by approximately 70% without significant changes in the amount of IMDG. Insulin-stimulated phosphorylation levels of insulin receptor (IR), IR substrate-1, and Akt were reduced in parallel with the decrease in insulin sensitivity. Furthermore, tyrosine phosphatase 1B (PTP1B), a protein known to inhibit insulin action by dephosphorylating IR, was activated, and PTP1B inhibition canceled HCI-induced insulin resistance. In conclusion, HCI causes insulin resistance in the fast-twitch–predominant plantaris muscle as well as in the slow-twitch–predominant soleus muscle, and HFD potentiates these effects in both muscle types. However, the mechanism differed between soleus and plantaris muscles, since insulin resistance was mediated by the PTP1B inhibition at IR in plantaris muscle. |
| first_indexed | 2024-03-13T05:38:35Z |
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| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-03-13T05:38:35Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-679f5dd1cbf64525a1e88f561ea72b202023-06-14T04:53:22ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2023-06-011410.3389/fphys.2023.11983901198390Physical inactivity induces insulin resistance in plantaris muscle through protein tyrosine phosphatase 1B activation in miceSaori Kakehi0Saori Kakehi1Yoshifumi Tamura2Yoshifumi Tamura3Shin-ichi Ikeda4Shin-ichi Ikeda5Naoko Kaga6Hikari Taka7Yuya Nishida8Ryuzo Kawamori9Ryuzo Kawamori10Hirotaka Watada11Hirotaka Watada12Department of Metabolism and Endocrinology, Tokyo, JapanSportology Center, Tokyo, JapanDepartment of Metabolism and Endocrinology, Tokyo, JapanSportology Center, Tokyo, JapanDepartment of Metabolism and Endocrinology, Tokyo, JapanSportology Center, Tokyo, JapanDivision of Proteomics and Biomolecular Science, Juntendo University Graduate School of Medicine, Tokyo, JapanDivision of Proteomics and Biomolecular Science, Juntendo University Graduate School of Medicine, Tokyo, JapanDepartment of Metabolism and Endocrinology, Tokyo, JapanDepartment of Metabolism and Endocrinology, Tokyo, JapanSportology Center, Tokyo, JapanDepartment of Metabolism and Endocrinology, Tokyo, JapanSportology Center, Tokyo, JapanInactivity causes insulin resistance in skeletal muscle and exacerbates various lifestyle-related diseases. We previously found that 24-h hindlimb cast immobilization (HCI) of the predominantly slow-twitch soleus muscle increased intramyocellular diacylglycerol (IMDG) and insulin resistance by activation of lipin1, and HCI after a high-fat diet (HFD) further aggravated insulin resistance. Here, we investigated the effects of HCI on the fast-twitch–predominant plantaris muscle. HCI reduced the insulin sensitivity of plantaris muscle by approximately 30%, and HCI following HFD dramatically reduced insulin sensitivity by approximately 70% without significant changes in the amount of IMDG. Insulin-stimulated phosphorylation levels of insulin receptor (IR), IR substrate-1, and Akt were reduced in parallel with the decrease in insulin sensitivity. Furthermore, tyrosine phosphatase 1B (PTP1B), a protein known to inhibit insulin action by dephosphorylating IR, was activated, and PTP1B inhibition canceled HCI-induced insulin resistance. In conclusion, HCI causes insulin resistance in the fast-twitch–predominant plantaris muscle as well as in the slow-twitch–predominant soleus muscle, and HFD potentiates these effects in both muscle types. However, the mechanism differed between soleus and plantaris muscles, since insulin resistance was mediated by the PTP1B inhibition at IR in plantaris muscle.https://www.frontiersin.org/articles/10.3389/fphys.2023.1198390/fullinsulin resistancephysical inactivityhigh fat dietskeletal musclePTP1B |
| spellingShingle | Saori Kakehi Saori Kakehi Yoshifumi Tamura Yoshifumi Tamura Shin-ichi Ikeda Shin-ichi Ikeda Naoko Kaga Hikari Taka Yuya Nishida Ryuzo Kawamori Ryuzo Kawamori Hirotaka Watada Hirotaka Watada Physical inactivity induces insulin resistance in plantaris muscle through protein tyrosine phosphatase 1B activation in mice Frontiers in Physiology insulin resistance physical inactivity high fat diet skeletal muscle PTP1B |
| title | Physical inactivity induces insulin resistance in plantaris muscle through protein tyrosine phosphatase 1B activation in mice |
| title_full | Physical inactivity induces insulin resistance in plantaris muscle through protein tyrosine phosphatase 1B activation in mice |
| title_fullStr | Physical inactivity induces insulin resistance in plantaris muscle through protein tyrosine phosphatase 1B activation in mice |
| title_full_unstemmed | Physical inactivity induces insulin resistance in plantaris muscle through protein tyrosine phosphatase 1B activation in mice |
| title_short | Physical inactivity induces insulin resistance in plantaris muscle through protein tyrosine phosphatase 1B activation in mice |
| title_sort | physical inactivity induces insulin resistance in plantaris muscle through protein tyrosine phosphatase 1b activation in mice |
| topic | insulin resistance physical inactivity high fat diet skeletal muscle PTP1B |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2023.1198390/full |
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