Dexamethasone treatment causes resistance to insulin-stimulated cellular potassium uptake in the rat.

Abstract

Patients treated with glucocorticoids have elevated skeletal muscle ouabain binding sites. The major Na(+)-K(+)-ATPase (NKA) isoform proteins found in muscle, alpha2 and beta1, 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 K+ 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(-1).day(-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 (K+(inf)) 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. K+(inf) (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 alpha2-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 alpha1-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.

• Authors: Michael S Rhee, Anjana Perianayagam, Pei Chen, Jang H Youn, Alicia A McDonough
• Journal: American journal of physiology. Cell physiology (Am J Physiol Cell Physiol) Vol. 287 Issue 5 Pg. C1229-37 (Nov 2004) ISSN: 0363-6143 [Print] United States
• PMID: 15213056 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Blood Glucose
• Glucocorticoids
• Insulin
• Isoenzymes
• Dexamethasone
• Sodium-Potassium-Exchanging ATPase
• Glucose
• Potassium

Topics

• Animals
• Blood Glucose (drug effects, metabolism)
• Dexamethasone (pharmacology)
• Dose-Response Relationship, Drug
• Glucocorticoids (pharmacology)
• Glucose (metabolism)
• Glucose Clamp Technique
• Immunoblotting
• Insulin (metabolism, pharmacology)
• Insulin Resistance (physiology)
• Isoenzymes (metabolism)
• Male
• Potassium (blood, metabolism, urine)
• Rats
• Rats, Sprague-Dawley
• Sodium-Potassium-Exchanging ATPase (metabolism)