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Mechanism discovered for muscle wasting seen in diabetes, AIDS and other diseases

BOSTON -- Muscle wasting is associated with aging and a serious consequence of different diseases, including cancer and diabetes. Researchers at Joslin Diabetes Center, with the assistance of other collaborating researchers, have discovered an important biochemical pathway for muscle wasting--as well as a potential target for drug therapy. The study will be published in the Oct. 15 issue of the journal Cell.

Muscle wasting is a hallmark of a number of diseases, including cancer, bacterial sepsis, AIDS, diabetes, and end-stage heart, kidney and obstructive pulmonary disease. Muscle wasting can cause generalized weakness and debilitation and in its extreme, when respiratory muscles are involved, asphyxia and even death.

Dongsheng Cai, M.D., Ph.D., a postdoctoral Fellow at Joslin Diabetes Center and Steven Shoelson, M.D., Ph.D., Helen and Morton Adler Chair and Associate Research Director at Joslin Diabetes Center, and Professor of Medicine at Harvard Medical School in Boston, along with their colleagues at Joslin, Beth Israel Deaconess Medical Center, The Children's Hospital Boston, Spaulding Rehabilitation Hospital, and Regeneron Pharmaceuticals in Tarrytown, NY, used transgenic (genetically altered) mice to study the biochemical pathways underlying muscle wasting. Their studies zeroed in on a transcription factor called NF-kB, which is well known for its importance in immune cells but was previously not known to be a critical mediator of muscle wasting.

The investigators created two different strains of transgenic mice--MIKK mice, in which NF-kB was activated selectively in muscle tissue, and MISR mice, in which NF-kB activation was inhibited in muscle. The MIKK mice were viable and appeared normal at birth, but as they matured, their body weight was reduced due to decreases in skeletal muscle mass. Their muscle fibers were also smaller than those of their non-genetically altered littermates. On the other hand, the MISR mice were
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Contact: Marjorie Dwyer
marjorie.dwyer@joslin.harvard.edu
617-732-2415
Joslin Diabetes Center
14-Oct-2004


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