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369 EFFECTS OF DEXAMETHASONE ON INSULIN-STIMULATED K+ UPTAKE: EVIDENCE FOR DEXAMETHASONE INDUCED INSULIN RESISTANCE
  1. M. Rhee,
  2. A. Perianayagam,
  3. P. Chen,
  4. J. H. Youn,
  5. A. A. McDonough
  1. USC Keck School of Medicine, Los Angeles

Abstract

Background Patients treated with adrenal steroids for chronic obstructive lung disease have elevated skeletal muscle ouabain binding sites. We have recently shown that rats treated for 14 days with the synthetic glucocorticoid dexamethasone (dex) have 50% increases in Na,K-ATPase (NKA) α2 and β1 isoform protein levels, the major isoform in muscle. These findings raise the concern that in this group acute stimulation of an increased pool of muscle NKA by catecholamines or insulin could precipitate acute hypokalemia.

Aim determine if the dex induced increase in muscle sodium pumps provokes an increase in insulin stimulated cellular K+ uptake. Alternatively, dex treatment could provoke insulin resistance of cellular K+ uptake analogous to dex induced insulin resistance of glucose uptake.

Method Rats were treated with dex (0.1 mg/kg/day) or vehicle via subcutaneous osmotic mini-pumps for 7 days (n=6 each). Vehicle infused rats were paired by weight to dex infused rats since dex treatment slowed weight gain. In conscious rats with tail venous and arterial cannulas, insulin (5 mU/kg.min) stimulated cellular uptake of K+ and glucose were measured by determining the amount of exogenous K+ infusion (Kinf) and glucose infusion (Ginf) needed to clamp plasma K+ and glucose at their baseline levels, measured at 10 min intervals over 2.5 hrs.

Results In the dex treated group insulin stimulated cellular uptake of glucose was reduced, as expected (Ginf (mmol/kg/hr): 10.2 ± 0.6 in shams, 5.2 ± 0.6 in dex treated). Insulin stimulated cellular uptake of K+ was, likewise, reduced (Kinf (μmol/kg/hr): 533 ± 77 in shams, 266 ± 82 in dex treated). NKA α2 levels in dex treated group, measured by immunoblots, were increased 1.67 ± 0.03 fold in gastrocnemius and 1.35 ± 0.1 in soleus; NKA α1 levels were unchanged.

Conclusion These results demonstrate that although dexamethasone treatment significantly increases muscle Na K ATPase levels, insulin stimulated cellular K+ uptake is significantly depressed, novel evidence for insulin resistance of K+ clearance during chronic dexamethasone treatment. DK057678.

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