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• W1996983786 abstract "Despite the important physiological role of insulin in the regulation of ionic homeostasis, primarily mediated by the Na+/K+-ATPase and Na+/K+/2Cl– cotransporter, the intracellular signalling molecules mediating this effect of insulin have not been elucidated. Treatment of 3T3-L1 fibroblasts with insulin increased total 86Rb+ (K+) uptake from 0.8 ± 0.04 to 1.02 ± 0.05 nmol · mg–1· protein–1· min–1 (p < 0.005). These changes in K+ flux, though small, can alter the membrane potential. Uptake occurred through both the Na+/K+-ATPase and Na+/K+/2Cl– cotransporter and both were stimulated by insulin. Interestingly, when bumetanide was used to inhibit the Na+/K+/2Cl– cotransporter prior to insulin action, no increase in 86Rb+ uptake via the Na+/K+-ATPase was observed. The structurally distinct phosphatidylinositol 3-kinase inhibitors wortmannin (50–200 nmol/l) and LY294 002 (50 μmol/l) attenuated both total insulin-stimulated 86Rb+ uptake as well as uptake via the Na+/K+-ATPase and Na+/K+/2Cl– cotransporter. Neither the inhibitor of p70 S6 kinase activation, rapamycin (30 ng/ml) nor the mitogen activated protein kinase kinase inhibitor, PD098 059 (50 μmol/l), had any effect on insulin's stimulation of K+ influx. A 10 μmol/l concentration of the protein kinase C (PKC) inhibitor bisindolylmaleimide attenuated insulin action but at 1 μmol/l it was ineffective, suggesting involvement of the atypical PKC-ζ isoform. We conclude that insulin-stimulated K+ uptake in 3T3-L1 fibroblasts appears to involve concerted regulation of both the Na+/K+-ATPase and Na+/K+/2Cl– cotransporter and we show for the first time that this process is signalled via a pathway involving phosphatidylinositol 3-kinase and PKC-ζ. [Diabetologia (1998) 41: 1199–1204]" @default.
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• W1996983786 date "1998-09-18" @default.
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• W1996983786 title "Insulin stimulation of K + uptake in 3T3-L1 fibroblasts involves phosphatidylinositol 3-kinase and protein kinase C-zeta" @default.
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• W1996983786 doi "https://doi.org/10.1007/s001250051052" @default.
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