Passive stretching produces Akt- and MAPK-dependent augmentations of GLUT4 translocation and glucose uptake in skeletal muscles of mice
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Muscle contraction is accompanied by passive stretching or deformation of cells and tissues. The present study aims to clarify whether or not acute passive stretching evokes glucose transporter 4 (GLUT4) translocation and glucose uptake in skeletal muscles of mice. Passive stretching mainly induced GLUT4 translocation from an intracellular membrane-rich fraction (PF5) to a plasma membrane-rich fraction (F2) and accelerated glucose uptake in hindlimb muscles; whereas electrical stimulation, which mimics physical exercise in vivo, and insulin, each induced GLUT4 translocation from an intracellular membrane-rich fraction (PF5) to a fraction rich in plasma membrane (F2), and to one rich in transverse tubules (PF3), along with subsequent glucose uptake. Mechanical stretching increased phosphorylation of Akt and p38 mitogen-activated protein kinase (p38 MAPK), but it had no apparent effect on the activity of AMP-activated protein kinase (AMPK). Electrical stimulation augmented the activity of not only AMPK but also phosphorylation of Akt and p38 MAPK. Our results suggest that passive stretching produces translocation of GLUT4 mainly from the fraction rich in intracellular membrane to that rich in plasma membrane, and that the glucose uptake could be Akt- and p38 MAPK-dependent, but AMPK-independent manners.
KeywordsAkt AMPK Contraction Glucose uptake GLUT4 translocation Mechanical stretching P38 MAPK Skeletal muscle
The present study was supported in part by grants-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, by grants from the Shizuoka Research and Development Foundation, and by The Nakatomi Foundation.
- 1.Ai H, Ihlemann J, Hellsten Y, Lauritzen HPMM, Hardie DG, Galbo H, Ploug T (2002) Effect of fiber type and nutritional state on AICAR- and contraction-stimulated glucose transport in rat muscle. Am J Physiol 282:E1291–E1300Google Scholar
- 11.Douen AG, Ramlal T, Rastogi S, Bilan PJ, Cartee GD, Vranic M, Holloszy JO, Klip A (1990) Exercise induces recruitment of the “insulin-responsive glucose transporter”. Evidence for distinct intracellular insulin- and exercise-recruitable transporter pools in skeletal muscle. J Biol Chem 265:13427–13430PubMedGoogle Scholar
- 13.Fujishiro M, Gotoh Y, Katagiri H, Sakoda H, Ogihara T, Anai M, Onishi Y, Ono H, Funaki M, Inukai K, Fukushima Y, Kikuchi M, Oka Y, Asano T (2001) MKK6/3 and p38 MAPK pathway activation is not necessary for insulin-induced glucose uptake but regulates glucose transporter expression. J Biol Chem 276:19800–19806CrossRefPubMedGoogle Scholar
- 20.Holmes BF, Lang DB, Birnbaum MJ, Mu J, Dohm GL (2004) AMP kinase is not required for the GLUT4 response to exercise and denervation in skeletal muscle. Am J Physiol 287:E739–E743Google Scholar
- 22.Hornberger TA, Armstrong DD, Koh TJ (2005) Intracellular signaling specificity in response to uniaxial vs. multiaxial stretch: implications for mechanotransduction. Am J Physiol 288:C185–C194Google Scholar
- 25.Ito Y, Ikeda R, Obara K, Nakayama K (2004) Passive stretch produces AMPK-independent translocation of GLUT4 and augmentation of glucose uptake in murine skeletal muscles. Physiologist 47:330Google Scholar
- 39.Sakamoto K, Aschenbach WG, Hirshman MF, Goodyear LJ (2003) Akt signaling in skeletal muscle: regulation by exercise and passive stretch. Am J Physiol 285:E1081–E1088Google Scholar
- 42.Suzuma I, Suzuma K, Ueki K, Hata Y, Feener EP, King GL, Aiello LP (2002) Stretch-induced retinal vascular endothelial growth factor expression is mediated by phosphatidylinositol 3-kinase and protein kinase C (PKC)-zeta but not by stretch-induced ERK1/2, Akt, Ras, or classical/novel PKC pathway. J Biol Chem 277:1047–1057CrossRefPubMedGoogle Scholar
- 47.Wojtaszewski JF, Higaki Y, Hirshman MF, Michael MD, Dufresne SD, Kahn CR, Goodyear LJ (1999) Exercise modulates photoreceptor insulin signaling and glucose transport in muscle-specific insulin receptor knockout mice. J Clin Invest 1041:1257–1264Google Scholar
- 48.Wojtaszewski JF, Nielsen JN, Jorgensen SB, Frosig C, Birk JB, Richter EA (2003) Transgenic models—a scientific tool to understand exercise-induced metabolism: the regulatory role of AMPK (5′-AMP-activated protein kinase) in glucose transport and glycogen synthase activity in skeletal muscle. Biochem Soc Trans 31:1290–1294PubMedGoogle Scholar