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Opposite effects of glucose on plasma membrane Ca2+-ATPase and Na/Ca exchanger transcription, expression, and activity in rat pancreatic beta-cells.

par Ximenes, Helena Maria;Kamagate, Adama ;Van Eylen, Françoise ;Carpinelli, Angelo;Herchuelz, André
Référence The Journal of biological chemistry, 278, 25, page (22956-22963)
Publication Publié, 2003-06

Article révisé par les pairs

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Résumé :

When stimulated by glucose the pancreatic beta-cell displays large oscillations of the intracellular free Ca2+concentration, resulting from intermittent Ca2+ entry from the outside and outflow from the inside, the latter process being mediated by the plasma membrane Ca2+-ATPase (PMCA) and the Na+/Ca2+ exchanger (NCX). To understand the respective role of these two mechanisms, we studied the effect of glucose on PMCA and NCX transcription, expression, and activity in rat pancreatic islet cells. Glucose (11.1 and 22.2 mm) induced a parallel decrease in PMCA transcription, expression, and activity. In contrast the sugar induced a parallel increase in NCX transcription, expression, and activity. The effects of the sugar were mimicked by the metabolizable insulin secretagogue alpha-ketoisocaproate and persisted in the presence of the Ca2+-channel blocker nifedipine. The above results are compatible with the view that, when stimulated, the beta-cell switches from a low efficiency Ca2+-extruding mechanism, the PMCA, to a high capacity system, the Na/Ca exchanger, to better face the increase in Ca2+ inflow. These effects of glucose do not result from a direct effect of the sugar itself and are not mediated by the increase in intracellular free Ca2+ concentration induced by the sugar.