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Topical Review |
1 Departments of Internal Medicine and Cellular and Molecular Physiology, Yale University School of Medicine, Howard Hughes Medical Institute, New Haven, CT, USA
While it has been known for more than 75 years that physical activity is associated with increased mitochondrial content in muscle, the molecular mechanism for this adaptive process has only recently been elucidated. This brief review examines existing studies that have identified AMPK-activated protein kinase (AMPK) and several other key regulators of mitochondrial biogenesis, including peroxisome proliferator-activated receptor-
coactivator-1
and -1ß, calcium/calmodulin-dependent protein kinase IV, and nitric oxide. In addition, the potential role of mitochondrial dysfunction in the pathogenesis of insulin resistance associated with ageing and type 2 diabetes mellitus is also discussed.
(Received 27 March 2006;
accepted after revision 15 May 2006;
first published online 18 May 2006)
Corresponding author G. I. Shulman: Yale University School of Medicine, Howard Hughes Medical Institute, New Haven, CT, USA. Email: gerald.shulman{at}yale.edu
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