| First Author | Otani K | Year | 2006 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 291 |
| Issue | 3 | Pages | E544-8 |
| PubMed ID | 16705056 | Mgi Jnum | J:112313 |
| Mgi Id | MGI:3656102 | Doi | 10.1152/ajpendo.00510.2005 |
| Citation | Otani K, et al. (2006) Inhibition of calpain results in impaired contraction-stimulated GLUT4 translocation in skeletal muscle. Am J Physiol Endocrinol Metab 291(3):E544-8 |
| abstractText | 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. |
