Journal
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
Volume 295, Issue 3, Pages E545-E552Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.90259.2008
Keywords
adenosine 5'-monophosphate-activated protein kinase
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Funding
- European Foundation for the Study of Diabetes
- Swedish Research Council
- Swedish Diabetes Association
- Strategic Research Foundation
- Knut and Alice Wallenberg Foundation
- Commission of the European Communities [LSHM-CT-2004-005272 EXGENESIS, LSHM-CT-2004-512013 EUGENE2]
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Skeletal muscle fibers differ considerably in their metabolic and physiological properties. Skeletal muscle displays a high degree of metabolic flexibility, which allows the myofibers to adapt to various physiological demands by shifting energy substrate utilization. Transcriptional events play a pivotal role in the metabolic adaptations of skeletal muscle. The expression of genes essential for skeletal muscle glucose and lipid metabolism is tightly coordinated in support of a shift in substrate utilization. AMP-activated protein kinase (AMPK) and calcineurin (a calcium-regulated serine/threonine protein phosphatase) regulate skeletal muscle metabolic gene expression programs in response to changes in the energy status and levels of neuronal input, respectively. AMPK and calcineurin activate transcriptional regulators such as peroxisome proliferator-activated receptor-gamma coactivator-1 alpha and myocyte enhancer factor as well as increase skeletal muscle oxidative capacity and mitochondrial gene expression. Activation of either the AMPK or calcineurin pathway can also enhance the glycogen storage capacity and insulin sensitivity in skeletal muscle. Characterization of pathways governing skeletal muscle metabolism offers insight into physiological and pharmacological strategies to prevent or ameliorate peripheral insulin resistance associated with metabolic disorders such as type 2 diabetes.
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