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|Title:||Calpain system regulates muscle mass and glucose transporter GLUT4 turnover|
Ford, Eric L.
García-Roves, Pablo M. (Pablo Miguel)
Bell, Graeme I.
Holloszy, John O.
Polonsky, Kenneth S.
|Publisher:||American Society for Biochemistry and Molecular Biology|
|Abstract:||The experiments in this study were undertaken to determine whether inhibition of calpain activity in skeletal muscle is associated with alterations in muscle metabolism. Transgenic mice that overexpress human calpastatin, an endogenous calpain inhibitor, in skeletal muscle were produced. Compared with wild type controls, muscle calpastatin mice demonstrated normal glucose tolerance. Levels of the glucose transporter GLUT4 were increased more than 3-fold in the transgenic mice by Western blotting while mRNA levels for GLUT4 and myocyte enhancer factors, MEF 2A and MEF 2D, protein levels were decreased. We found that GLUT4 can be degraded by calpain-2, suggesting that diminished degradation is responsible for the increase in muscle GLUT4 in the calpastatin transgenic mice. Despite the increase in GLUT4, glucose transport into isolated muscles from transgenic mice was not increased in response to insulin. The expression of protein kinase B was decreased by approximately 60% in calpastatin transgenic muscle. This decrease could play a role in accounting for the insulin resistance relative to GLUT4 content of calpastatin transgenic muscle. The muscle weights of transgenic animals were substantially increased compared with controls. These results are consistent with the conclusion that calpain-mediated pathways play an important role in the regulation of GLUT4 degradation in muscle and in the regulation of muscle mass. Inhibition of calpain activity in muscle by overexpression of calpastatin is associated with an increase in GLUT4 protein without a proportional increase in insulin-stimulated glucose transport. These findings provide evidence for a physiological role for calpains in the regulation of muscle glucose metabolism and muscle mass.|
|Note:||Reproducció del document publicat a: https://doi.org/10.1074/jbc.M400213200|
|It is part of:||Journal of Biological Chemistry, 2004, vol. 279, num. 20, p. 20915-20920|
|Appears in Collections:||Articles publicats en revistes (Ciències Fisiològiques)|
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