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This Article Full Text Full Text (PDF) All Versions of this Article: 291/3/E544    most recent 00510.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Otani, K. Articles by Han, D.-H. Search for Related Content PubMed PubMed Citation Articles by Otani, K. Articles by Han, D.-H.

Inhibition of calpain results in impaired contraction-stimulated GLUT4 translocation in skeletal muscle

Department of Medicine, Washington University School of Medicine, St. Louis, Missouri

Submitted 21 October 2005 ; accepted in final form 13 April 2006

It was previously found that transgenic mice that overexpress the calpain inhibitor calpastatin (CsTg) have an 3-fold increase in GLUT4 protein in their skeletal muscles. Despite the increase in GLUT4, which appears to be due to inhibition of its proteolysis by calpain, insulin-stimulated glucose transport is not increased in CsTg muscles. PKB (Akt) protein level is reduced 60% in CsTg muscles, suggesting a possible mechanism for the relative insulin resistance. Muscle contractions stimulate glucose transport by a mechanism that is independent of insulin signaling. The purpose of this study was to test the hypothesis that the threefold increase in GLUT4 in CsTg would result in a large increase in contraction-stimulated glucose transport. CAMKII and AMPK mediate steps in the contraction-stimulated pathway. The protein levels of AMPK and CAMKII were increased three- to fourfold in CsTg muscles, suggesting that these proteins are also calpain substrates. Despite the large increases in GLUT4, AMPK, and CAMKII, contraction-stimulated GLUT4 translocation and glucose transport were not increased above wild-type values. These findings suggest that inhibition of calpain results in impairment of a step in the GLUT4 translocation process downstream of the insulin- and contraction-signaling pathways. They also provide evidence that CAMKII and AMPK are calpain substrates.

adenosine monophosphate-activated protein kinase; calpastatin; calcium/calmodulin-dependent protein kinase-II

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