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1 Physiology and Biophysics, University of Southern California Keck School of Medicine, Los Angeles, CA, USA
* To whom correspondence should be addressed. E-mail: mcdonoug{at}usc.edu.
Patients treated with glucocorticoids have elevated skeletal muscle ouabain binding sites. The major Na,K-ATPase (NKA) isoform proteins found in muscle: 
2 and 
1, are increased 50% in rats treated for 14 days with the synthetic glucocorticoid dexamethasone (dex). This study addressed whether the dex induced increase in muscle NKA pool leads to increased insulin stimulated cellular K+ uptake which could precipitate hypokalemia. Rats were treated with dex or vehicle via osmotic mini-pumps at one of two doses: 0.02 mg/kg/day for 14 days ("low dex," n=5 pairs) or 0.1 mg/kg/day for 7 days ("high dex," n=6 pairs). Insulin was infused at 5 mU/kg.min over 2.5 hr in conscious rats. Insulin stimulated cellular K+ and glucose uptake rates were assessed in vivo by measuring the exogenous K+ infusion (Kinf) and glucose infusion (Ginf) rates needed to maintain constant plasma [K+] and [glucose] during insulin infusion. Dex at both doses decreased insulin stimulated glucose uptake, as previously reported. Ginf (mmol/kg/hr) was 10.2 ± 0.6 in vehicle, 5.8 ± 0.8 in low dex and 5.2 ± 0.6 in high dex treated. High dex also reduced insulin stimulated K+ uptake. Kinf (mmol/kg/hr) was 0.53 ± 0.08 in vehicle, 0.49 ± 0.14 in low dex and 0.27 ± 0.08 in high dex treated rats. Dex treatment did not alter urinary K+ excretion. NKA 2 levels in the low dex treated group, measured by immunoblots, were unchanged, but increased 38 ± 15 % (soleus) and 67 ± 3 % (gastrocnemius) in the high dex group; NKA 1 was unchanged. These results provide novel evidence for insulin resistance of K+ clearance during chronic dexamethasone treatment: insulin stimulated cellular K+ uptake is significantly depressed despite increased muscle sodium pump pool size.
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