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SGK1 dependence of insulin induced hypokalemia

  • Signaling and Cell Physiology
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Abstract

Insulin stimulates cellular K+ uptake leading to hypokalemia. Cellular K+ uptake is accomplished by parallel stimulation of Na+/H+ exchange, Na+,K+,2Cl co-transport, and Na+/K+ ATPase and leads to cell swelling, a prerequisite for several metabolic effects of the hormone. Little is known about underlying signaling. Insulin is known to activate the serum and glucocorticoid-inducible kinase SGK1, which in turn enhances the activity of all three transport proteins. The present study thus explored the contribution of SGK1 to insulin-induced hypokalemia. To this end, gene-targeted mice lacking SGK1 (sgk1 −/−) and their wild-type littermates (sgk1 +/+) have been infused with insulin (2 mU kg−1 min−1) and glucose at rates leaving the plasma glucose concentration constant. Moreover, isolated liver perfusion experiments have been performed to determine stimulation of cellular K+ uptake by insulin (100 nM). As a result, combined glucose and insulin infusion significantly decreased plasma K+ concentration despite a significant decrease of urinary K+ excretion in sgk1 +/+ but not in sgk1 −/− mice. Accordingly, the plasma K+ concentration was within 60 min significantly lower in sgk1 +/+ than in sgk1 −/− mice. In isolated liver perfusion experiments, cellular K+ uptake was stimulated by insulin (100 nM), an effect blunted by 72% in sgk1 −/− mice as compared to sgk1 +/+ mice. Accordingly, insulin-induced cell hydration was 63% lower in sgk1 −/− mice than in sgk1 +/+mice. Moreover, volume regulatory K+ release was 31% smaller in sgk1 −/− mice than in sgk1 +/+ mice. In conclusion, the serum and glucocorticoid-inducible kinase SGK1 participates in the signaling mediating the hypokalemic effect of insulin.

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Acknowledgments

This work was supported by grants from DFG and BMBF (D.K., F.L, D.H., D.G.).

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Correspondence to Florian Lang.

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Boini, K.M., Graf, D., Kuhl, D. et al. SGK1 dependence of insulin induced hypokalemia. Pflugers Arch - Eur J Physiol 457, 955–961 (2009). https://doi.org/10.1007/s00424-008-0559-5

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