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Telmisartan Improves Insulin Resistance of Skeletal Muscle Through Peroxisome Proliferator–Activated Receptor-δ Activation
The mechanisms of the improvement of glucose homeostasis through angiotensin receptor blockers are not fully elucidated in hypertensive patients. We investigated the effects of telmisartan on insulin signaling and glucose uptake in cultured myotubes and skeletal muscle from wild-type and muscle-spec...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581229/ https://www.ncbi.nlm.nih.gov/pubmed/23238297 http://dx.doi.org/10.2337/db12-0570 |
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author | Li, Li Luo, Zhidan Yu, Hao Feng, Xiaoli Wang, Peijian Chen, Jian Pu, Yunfei Zhao, Yu He, Hongbo Zhong, Jian Liu, Daoyan Zhu, Zhiming |
author_facet | Li, Li Luo, Zhidan Yu, Hao Feng, Xiaoli Wang, Peijian Chen, Jian Pu, Yunfei Zhao, Yu He, Hongbo Zhong, Jian Liu, Daoyan Zhu, Zhiming |
author_sort | Li, Li |
collection | PubMed |
description | The mechanisms of the improvement of glucose homeostasis through angiotensin receptor blockers are not fully elucidated in hypertensive patients. We investigated the effects of telmisartan on insulin signaling and glucose uptake in cultured myotubes and skeletal muscle from wild-type and muscle-specific peroxisome proliferator–activated receptor (PPAR) δ knockout (MCK-PPARδ(−/−)) mice. Telmisartan increased PPARδ expression and activated PPARδ transcriptional activity in cultured C2C12 myotubes. In palmitate-induced insulin-resistant C2C12 myotubes, telmisartan enhanced insulin-stimulated Akt and Akt substrate of 160 kDa (AS160) phosphorylation as well as Glut4 translocation to the plasma membrane. These effects were inhibited by antagonizing PPARδ or phosphatidylinositol-3 kinase, but not by PPARγ and PPARα inhibition. Palmitate reducing the insulin-stimulated glucose uptake in C2C12 myotubes could be restored by telmisartan. In vivo experiments showed that telmisartan treatment reversed high-fat diet–induced insulin resistance and glucose intolerance in wild-type mice but not in MCK-PPARδ(−/−) mice. The protein levels of PPARδ, phospho-Akt, phospho-AS160, and Glut4 translocation to the plasma membrane in the skeletal muscle on insulin stimulation were reduced by high-fat diet and were restored by telmisartan administration in wild-type mice. These effects were absent in MCK-PPARδ(−/−) mice. These findings implicate PPARδ as a potential therapeutic target in the treatment of hypertensive subjects with insulin resistance. |
format | Online Article Text |
id | pubmed-3581229 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-35812292014-03-01 Telmisartan Improves Insulin Resistance of Skeletal Muscle Through Peroxisome Proliferator–Activated Receptor-δ Activation Li, Li Luo, Zhidan Yu, Hao Feng, Xiaoli Wang, Peijian Chen, Jian Pu, Yunfei Zhao, Yu He, Hongbo Zhong, Jian Liu, Daoyan Zhu, Zhiming Diabetes Metabolism The mechanisms of the improvement of glucose homeostasis through angiotensin receptor blockers are not fully elucidated in hypertensive patients. We investigated the effects of telmisartan on insulin signaling and glucose uptake in cultured myotubes and skeletal muscle from wild-type and muscle-specific peroxisome proliferator–activated receptor (PPAR) δ knockout (MCK-PPARδ(−/−)) mice. Telmisartan increased PPARδ expression and activated PPARδ transcriptional activity in cultured C2C12 myotubes. In palmitate-induced insulin-resistant C2C12 myotubes, telmisartan enhanced insulin-stimulated Akt and Akt substrate of 160 kDa (AS160) phosphorylation as well as Glut4 translocation to the plasma membrane. These effects were inhibited by antagonizing PPARδ or phosphatidylinositol-3 kinase, but not by PPARγ and PPARα inhibition. Palmitate reducing the insulin-stimulated glucose uptake in C2C12 myotubes could be restored by telmisartan. In vivo experiments showed that telmisartan treatment reversed high-fat diet–induced insulin resistance and glucose intolerance in wild-type mice but not in MCK-PPARδ(−/−) mice. The protein levels of PPARδ, phospho-Akt, phospho-AS160, and Glut4 translocation to the plasma membrane in the skeletal muscle on insulin stimulation were reduced by high-fat diet and were restored by telmisartan administration in wild-type mice. These effects were absent in MCK-PPARδ(−/−) mice. These findings implicate PPARδ as a potential therapeutic target in the treatment of hypertensive subjects with insulin resistance. American Diabetes Association 2013-03 2013-02-14 /pmc/articles/PMC3581229/ /pubmed/23238297 http://dx.doi.org/10.2337/db12-0570 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Metabolism Li, Li Luo, Zhidan Yu, Hao Feng, Xiaoli Wang, Peijian Chen, Jian Pu, Yunfei Zhao, Yu He, Hongbo Zhong, Jian Liu, Daoyan Zhu, Zhiming Telmisartan Improves Insulin Resistance of Skeletal Muscle Through Peroxisome Proliferator–Activated Receptor-δ Activation |
title | Telmisartan Improves Insulin Resistance of Skeletal Muscle Through Peroxisome Proliferator–Activated Receptor-δ Activation |
title_full | Telmisartan Improves Insulin Resistance of Skeletal Muscle Through Peroxisome Proliferator–Activated Receptor-δ Activation |
title_fullStr | Telmisartan Improves Insulin Resistance of Skeletal Muscle Through Peroxisome Proliferator–Activated Receptor-δ Activation |
title_full_unstemmed | Telmisartan Improves Insulin Resistance of Skeletal Muscle Through Peroxisome Proliferator–Activated Receptor-δ Activation |
title_short | Telmisartan Improves Insulin Resistance of Skeletal Muscle Through Peroxisome Proliferator–Activated Receptor-δ Activation |
title_sort | telmisartan improves insulin resistance of skeletal muscle through peroxisome proliferator–activated receptor-δ activation |
topic | Metabolism |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581229/ https://www.ncbi.nlm.nih.gov/pubmed/23238297 http://dx.doi.org/10.2337/db12-0570 |
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