16705056

pubmed:Citation

3

It was previously found that transgenic mice that overexpress the calpain inhibitor calpastatin (CsTg) have an approximately 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 approximately 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.

eng

IM

MEDLINE

0193-1849

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NLM

E544-8

pubmed-meshheading:16705056-AMP-Activated Protein Kinases, pubmed-meshheading:16705056-Animals, pubmed-meshheading:16705056-Calcium-Binding Proteins, pubmed-meshheading:16705056-Calcium-Calmodulin-Dependent Protein Kinase Type 2, pubmed-meshheading:16705056-Calcium-Calmodulin-Dependent Protein Kinases, pubmed-meshheading:16705056-Calpain, pubmed-meshheading:16705056-Deoxyglucose, pubmed-meshheading:16705056-Gene Expression, pubmed-meshheading:16705056-Glucose Transporter Type 4, pubmed-meshheading:16705056-Glycogen, pubmed-meshheading:16705056-Mice, pubmed-meshheading:16705056-Mice, Transgenic, pubmed-meshheading:16705056-Multienzyme Complexes, pubmed-meshheading:16705056-Muscle, Skeletal, pubmed-meshheading:16705056-Muscle Contraction, pubmed-meshheading:16705056-Phosphorylation, pubmed-meshheading:16705056-Protein Transport, pubmed-meshheading:16705056-Protein-Serine-Threonine Kinases

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

Journal Article, Research Support, N.I.H., Extramural