期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 15, 期 7, 页码 1572-1581出版社
WILEY
DOI: 10.1111/j.1582-4934.2010.01085.x
关键词
peroxisome proliferator activated receptor delta; adenosine monophosphate-activated protein kinase; telmisartan; skeletal muscle; running endurance
资金
- Natural Science Foundation of China [30890042]
- National Basic Research Program (973 Program) of China [2006CB503905, 2006CB503804]
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 delta (PPAR-delta) 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-delta-deficient mice. Administration of telmisartan up-regulated levels of PPAR-delta and phospho-AMPK alpha in cultured myotubes. However, PPAR-delta gene deficiency completely abolished the telmisartan effect on phospho-AMPK alpha 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-delta-deficient mice. The mechanism is involved in PPAR-delta-mediated stimulation of the AMPK pathway. Compared to the control mice, phospho-AMPK alpha level in skeletal muscle was up-regulated in mice treated with telmisartan. In contrast, phospho-AMPK alpha expression in skeletal muscle was unchanged in PPAR-delta-deficient mice treated with telmisartan. These findings highlight the ability of telmisartan to improve skeletal muscle function, and they implicate PPAR-delta as a potential therapeutic target for the prevention of type 2 diabetes.
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