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Altered expression and insulin-induced trafficking of Na+-K+-ATPase in rat skeletal muscle: effects of high-fat diet and exercise.

Abstract
Skeletal muscle Na(+)-K(+)-ATPase plays a central role in the clearance of K(+) from the extracellular fluid, therefore maintaining blood [K(+)]. Na(+)-K(+)-ATPase activity in peripheral tissue is impaired in insulin resistant states. We determined effects of high-fat diet (HFD) and exercise training (ET) on skeletal muscle Na(+)-K(+)-ATPase subunit expression and insulin-stimulated translocation. Skeletal muscle expression of Na(+)-K(+)-ATPase isoforms and transcription factor DNA binding was determined before or after 5 days of swim training in Wistar rats fed chow or HFD for 4 or 12 wk. Skeletal muscle insulin resistance was observed after 12 wk of HFD. Na(+)-K(+)-ATPase alpha(1)-subunit protein expression was increased 1.6-fold (P < 0.05), whereas alpha(2)- and beta(1)-subunits and protein expression were decreased twofold (P < 0.01) in parallel with decrease in plasma membrane Na(+)-K(+)-ATPase activity after 4 wk of HFD. Exercise training restored alpha(1)-, alpha(2)-, and beta(1)-subunit expression and Na(+)-K(+)-ATPase activity to control levels and reduced beta(2)-subunit expression 2.2-fold (P < 0.05). DNA binding activity of the alpha(1)-subunit-regulating transcription factor ZEB (AREB6) and alpha(1) mRNA expression were increased after HFD and restored by ET. DNA binding activity of Sp-1, a transcription factor involved in the regulation of alpha(2)- and beta(1)-subunit expression, was decreased after HFD. ET increased phosphorylation of the Na(+)-K(+)-ATPase regulatory protein phospholemman. Phospholemman mRNA and protein expression were increased after HFD and restored to control levels after ET. Insulin-stimulated translocation of the alpha(2)-subunit to plasma membrane was impaired by HFD, whereas alpha(1)-subunit translocation remained unchanged. Alterations in sodium pump function precede the development of skeletal muscle insulin resistance. Disturbances in skeletal muscle Na(+)-K(+)-ATPase regulation, particularly the alpha(2)-subunit, may contribute to impaired ion homeostasis in insulin-resistant states such as obesity and type 2 diabetes.
AuthorsDana Galuska, Olga Kotova, Romain Barrès, Daria Chibalina, Boubacar Benziane, Alexander V Chibalin
JournalAmerican journal of physiology. Endocrinology and metabolism (Am J Physiol Endocrinol Metab) Vol. 297 Issue 1 Pg. E38-49 (Jul 2009) ISSN: 1522-1555 [Electronic] United States
PMID19366873 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Validation Study)
Chemical References
  • Dietary Fats
  • Insulin
  • Tritium
  • Ouabain
  • Sodium-Potassium-Exchanging ATPase
Topics
  • Animals
  • Diabetes Mellitus, Type 2 (complications, genetics, metabolism)
  • Diet, Atherogenic
  • Dietary Fats (pharmacology)
  • Female
  • Gene Expression Regulation, Enzymologic (drug effects)
  • Insulin (pharmacology)
  • Insulin Resistance (genetics)
  • Muscle, Skeletal (drug effects, metabolism, physiology)
  • Obesity (complications, genetics, metabolism)
  • Ouabain (pharmacokinetics)
  • Physical Conditioning, Animal (physiology)
  • Protein Transport (drug effects)
  • Rats
  • Rats, Wistar
  • Sodium-Potassium-Exchanging ATPase (genetics, metabolism)
  • Swimming
  • Tritium (pharmacokinetics)

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