Dataset Information

Angiotensin II receptor blocker telmisartan enhances running endurance of skeletal muscle through activation of the PPAR-?/AMPK pathway.

ABSTRACT: Clinical trials have shown that angiotensin II receptor blockers reduce the new onset of diabetes in hypertensives; however, the underlying mechanisms remain unknown. We investigated the effects of telmisartan on peroxisome proliferator activated receptor ? (PPAR-?) and the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway in cultured myotubes, as well as on the running endurance of wild-type and PPAR-?-deficient mice. Administration of telmisartan up-regulated levels of PPAR-? and phospho-AMPK? in cultured myotubes. However, PPAR-? gene deficiency completely abolished the telmisartan effect on phospho-AMPK?in vitro. Chronic administration of telmisartan remarkably prevented weight gain, enhanced running endurance and post-exercise oxygen consumption, and increased slow-twitch skeletal muscle fibres in wild-type mice, but these effects were absent in PPAR-?-deficient mice. The mechanism is involved in PPAR-?-mediated stimulation of the AMPK pathway. Compared to the control mice, phospho-AMPK? level in skeletal muscle was up-regulated in mice treated with telmisartan. In contrast, phospho-AMPK? expression in skeletal muscle was unchanged in PPAR-?-deficient mice treated with telmisartan. These findings highlight the ability of telmisartan to improve skeletal muscle function, and they implicate PPAR-? as a potential therapeutic target for the prevention of type 2 diabetes.

SUBMITTER: Feng X

PROVIDER: S-EPMC3823201 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Angiotensin II receptor blocker telmisartan enhances running endurance of skeletal muscle through activation of the PPAR-δ/AMPK pathway.

Feng Xiaoli X Luo Zhidan Z Ma Liqun L Ma Shuangtao S Yang Dachun D Zhao Zhigang Z Yan Zhencheng Z He Hongbo H Cao Tingbing T Liu Daoyan D Zhu Zhiming Z

Journal of cellular and molecular medicine 20100514 7

Clinical trials have shown that angiotensin II receptor blockers reduce the new onset of diabetes in hypertensives; however, the underlying mechanisms remain unknown. We investigated the effects of telmisartan on peroxisome proliferator activated receptor γ (PPAR-δ) and the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway in cultured myotubes, as well as on the running endurance of wild-type and PPAR-δ-deficient mice. Administration of telmisartan up-regulated levels of PPAR ...[more]

PMID: 20477906

Similar Datasets

Project description:Key pointsAMP-activated protein kinase (AMPK) is considered a major regulator of skeletal muscle metabolism during exercise. However, we previously showed that, although AMPK activity increases by 8-10-fold during ∼120 min of exercise at ∼65% V̇O2peak in untrained individuals, there is no increase in these individuals after only 10 days of exercise training (longitudinal study). In a cross-sectional study, we show that there is also a lack of activation of skeletal muscle AMPK during 120 min of cycling exercise at 65% V̇O2peak in endurance-trained individuals. These findings indicate that AMPK is not an important regulator of exercise metabolism during 120 min of exercise at 65% V̇O2peak in endurance trained men. It is important that more energy is directed towards examining other potential regulators of exercise metabolism.AbstractAMP-activated protein kinase (AMPK) is considered a major regulator of skeletal muscle metabolism during exercise. Indeed, AMPK is activated during exercise and activation of AMPK by 5-aminoimidazole-4-carboxyamide-ribonucleoside (AICAR) increases skeletal muscle glucose uptake and fat oxidation. However, we have previously shown that, although AMPK activity increases by 8-10-fold during ∼120 min of exercise at ∼65% V̇O2peak in untrained individuals, there is no increase in these individuals after only 10 days of exercise training (longitudinal study). In a cross-sectional study, we examined whether there is also a lack of activation of skeletal muscle AMPK during 120 min of cycling exercise at 65% V̇O2peak in endurance-trained individuals. Eleven untrained (UT; V̇O2peak = 37.9 ± 5.6 ml.kg-1 min-1 ) and seven endurance trained (ET; V̇O2peak = 61.8 ± 2.2 ml.kg-1 min-1 ) males completed 120 min of cycling exercise at 66 ± 4% V̇O2peak (UT: 100 ± 21 W; ET: 190 ± 15 W). Muscle biopsies were obtained at rest and following 30 and 120 min of exercise. Muscle glycogen was significantly (P < 0.05) higher before exercise in ET and decreased similarly during exercise in the ET and UT individuals. Exercise significantly increased calculated skeletal muscle free AMP content and more so in the UT individuals. Exercise significantly (P < 0.05) increased skeletal muscle AMPK α2 activity (4-fold), AMPK αThr172 phosphorylation (2-fold) and ACCβ Ser222 phosphorylation (2-fold) in the UT individuals but not in the ET individuals. These findings indicate that AMPK is not an important regulator of exercise metabolism during 120 min of exercise at 65% V̇O2peak in endurance trained men.

Dataset Information

Angiotensin II receptor blocker telmisartan enhances running endurance of skeletal muscle through activation of the PPAR-?/AMPK pathway.

Publications

Angiotensin II receptor blocker telmisartan enhances running endurance of skeletal muscle through activation of the PPAR-δ/AMPK pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets