Opposite Effects of Glucose on Plasma Membrane Ca2+-ATPase and Na/Ca Exchanger Transcription, Expression, and Activity in Rat Pancreatic β-Cells

• Published in: The Journal of biological chemistry 2003-06, Vol.278 (25), p.22956
• Main Authors: Helena Maria Ximenes, Adama Kamagate, Françoise Van Eylen, Angelo Carpinelli, André Herchuelz
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M212339200

When stimulated by glucose the pancreatic β-cell displays large oscillations of the intracellular free Ca 2 + concentration, resulting from intermittent Ca 2 + entry from the outside and outflow from the inside, the latter process being mediated by the plasma membrane Ca 2 + -ATPase (PMCA) and the Na + /Ca 2 + 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 m m ) 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 α-ketoisocaproate and persisted in the presence of the Ca 2 + -channel blocker nifedipine. The above results are compatible with the view that, when stimulated, the β-cell switches from a low efficiency Ca 2 + -extruding mechanism, the PMCA, to a high capacity system, the Na/Ca exchanger, to better face the increase in Ca 2 + 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 Ca 2 + concentration induced by the sugar.