| Autor: |
Rhee, Michael S., Perianayagam, Anjana, Pei Chen, Youn, Jang H., McDonough, Alicia A. |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Cell Physiology; Nov2004, Vol. 287 Issue 5, pC1229-C1237, 9p |
| Abstrakt: |
Patients treated with glucocorticoids have elevated skeletal muscle ouabain binding sites. The major Na+-K+-ATPase (NKA) isoform proteins found in muscle, α2 and β1, are increased by 50% in rats treated for 14 days with the synthetic glucocorticoid dexamethasone (DEX). This study addressed whether the DEX-induced increase in the muscle NKA pool leads to increased insulin-stimulated cellular K2+ uptake that could precipitate hypokalemia. Rats were treated with DEX or vehicle via osmotic minipumps at one of two doses: 0.02 mg.kg-1 .day-1 for 14 days (low DEX; n = 5 pairs) or 0.1 mg.kg-1day-1 for 7 days (high DEX; n 6 pairs). Insulin was infused at a rate of 5 mU.kg-1. min-1 over 2.5 h 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 concentrations during insulin infusion. DEX at both doses decreased insulin-stimulated glucose uptake as previously reported. Ginf (in mmol.kg-1 .h-1) was 10.2 ± 0.6 in vehicle-treated rats, 5.8 ± 0.8 in low-DEX-treated rats, and 5.2 ± 0.6 in high-DEX-treated rats. High DEX treatment also reduced insulin-stimulated K+ uptake. Kinf+ (in mmol.kg-1 h -1) was 0.53 ± 0.08 in vehicle-treated rats, 0.49 ± 0.14 in low-DEX-treated rats, and 0.27 ± 0.08 in high-DEX-treated rats. DEX treatment did not alter urinary K+ excretion. NKA α2-isoform levels in the low-DEX- treated group, measured by immunoblotting, were unchanged, but they increased by 38 ± 15% (soleus) and by 67 ± 3% (gastrocnemius) in the high-DEX treatment group. The NKA α1-isoform level was unchanged. These results provide novel evidence for the insulin resistance of K+ clearance during chronic DEX treatment. Insulin-stimulated cellular K+ uptake was significantly depressed despite increased muscle sodium pump pool size. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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