Myotonic dystrophy type 1 is the second most common form of muscular dystrophy and the form most likely to occur in adults. The disorder is characterized by weakness and atrophy of type 1 (or slow) muscle fibers through mechanisms that, until recently, were not understood. Now, Zhihua Gao and Thomas A. Cooper (Baylor College of Medicine, Houston, TX) have shown that aberrant alternative splicing is to blame for the muscle wasting. In type 1 muscle fibers, alternative splicing shifts expression of the enzyme pyruvate kinase to favor an embryonic isoform (PKM2) that alters glucose metabolism in the muscle cells, affecting their energy balance and potentially leading to atrophy (Proc. Natl. Acad. Sci. USA published online 29 July 2013; doi:10.1073/pnas.1308806110).
The research used mice engineered to express high levels of Pkm2 in type 1 skeletal muscle fibers and found that expression of Pkm2 resulted in the use of glucose instead of fat as fuel and increased activity-related energy expenditure. These changes disrupt cellular metabolic homeostasis and introduce energy deficits that may contribute to muscle wasting. As Cooper stated in a press release, “The muscle wasting in this disease could be due to an imbalance of metabolism.”
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