Activation of GLUT1 by metabolic and osmotic stress: Potential involvement of AMP-activated protein kinase (AMPK)

Kay Barnes*, Jean C. Ingram, Omar H. Porras, L. Felipe Barros, Emma R. Hudson, Lee G.D. Fryer, Fabienne Foufelle, David Carling, D. Grahame Hardie, Stephen A. Baldwin

*Autor correspondiente de este trabajo

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

257 Citas (Scopus)

Resumen

In the rat liver epithelial cell line Clone 9, the Vmax for glucose uptake is acutely increased by inhibition of oxidative phosphorylation and by osmotic stress. By using a membrane-impermeant photoaffinity labelling reagent together with an isoform-specific antibody, we have, for the first time, provided direct evidence for the involvement of the GLUT1 glucose transporter isoform in this response. Transport stimulation was found to be associated with enhanced accessibility of GLUT1 to its substrate and with photolabelling of formerly 'cryptic' exofacial substrate binding sites in GLUT1 molecules. The total amount of cell surface GLUT1 remained constant. The precise mechanism for this binding site 'unmasking' is unclear but appears to involve AMP-activated protein kinase: in the current study, osmotic and metabolic stresses were found to result in activation of the α1 isoform of AMP-activated protein kinase, and transport stimulation could be mimicked both by 5-aminoimidazole-4-carboxamide ribonucleoside and by infection of cells with a recombinant adenovirus encoding constitutively active AMP-activated protein kinase. The effect of 5-aminoimidazole-4-carboxamide ribonucleoside, as for metabolic stress, was on the Vmax rather than on the Km for transport and did not affect the cell-surface concentration of GLUT1. The relevant downstream target(s) of AMP-activated protein kinase have not yet been identified, but stimulation of transport by inhibition of oxidative phosphorylation or by 5-aminoimidazole-4-carboxamide ribonucleoside was not prevented by either inhibitors of conventional and novel protein kinase C isoforms or inhibitors of nitric oxide synthase. These enzymes, which have been implicated in stress-regulated pathways in other cell types, are therefore unlikely to play a role in transport regulation by stress in Clone 9 cells.

Idioma originalInglés
Páginas (desde-hasta)2433-2442
Número de páginas10
PublicaciónJournal of Cell Science
Volumen115
N.º11
EstadoPublicada - 2002
Publicado de forma externa

Áreas temáticas de ASJC Scopus

  • Biología celular

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