High glucose levels induce inhibition of Na,K-ATPase via stimulation of aldose reductase, formation of microtubules and formation of an acetylated tubulin/Na,K-ATPase complex

RIVELLI, J.F.; AMAIDEN, M.R.; MONESTEROLO, N.E.; PREVITALI, G; SANTANDER, V.S; FERNANDEZ, A.; ARCE, C.A.; CASALE, C.H

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2012 vol. 44 p. 1203 - 1203

ur previous studies demonstrated that acetylated tubulin forms a complex with Na+,K+-ATPase and thereby inhibits its enzyme activity in cultured COS and CAD cells. The enzyme activity was restored by treatment of cells with l-glutamate, which caused dissociation of the acetylated tubulin/Na+,K+-ATPase complex. Addition of glucose, but not elimination of glutamate, led to re-formation of the complex and inhibition of the Na+,K+-ATPase activity. The purpose of the present study was to elucidate the mechanism underlying this effect of glucose. We found that exposure of cells to high glucose concentrations induced: (a) microtubule formation; (b) activation of aldose reductase by the microtubules; (c) association of tubulin with membrane; (d) formation of the acetylated tubulin/Na+,K+-ATPase complex and consequent inhibition of enzyme activity. Exposure of cells to sorbitol caused similar effects. Studies on erythrocytes from diabetic patients and on tissues containing insulin-insensitive