TY - JOUR

T1 - Altered expression and insulin-induced trafficking of Na+-K+-ATPase in rat skeletal muscle

T2 - effects of high-fat diet and exercise

AU - Galuska, Dana

AU - Kotova, Olga

AU - Barres, Romain

AU - Chibalina, Daria

AU - Benziane, Boubacar

AU - Chibalin, Alexander V

PY - 2009/7

Y1 - 2009/7

N2 - 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.

AB - 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.

KW - Animals

KW - Diabetes Mellitus, Type 2

KW - Diet, Atherogenic

KW - Dietary Fats

KW - Female

KW - Gene Expression Regulation, Enzymologic

KW - Insulin

KW - Insulin Resistance

KW - Muscle, Skeletal

KW - Obesity

KW - Ouabain

KW - Physical Conditioning, Animal

KW - Protein Transport

KW - Rats

KW - Rats, Wistar

KW - Sodium-Potassium-Exchanging ATPase

KW - Swimming

KW - Tritium

U2 - 10.1152/ajpendo.90990.2008

DO - 10.1152/ajpendo.90990.2008

M3 - Journal article

C2 - 19366873

VL - 297

SP - E38-49

JO - A J P: Endocrinology and Metabolism (Online)

JF - A J P: Endocrinology and Metabolism (Online)

SN - 1522-1555

IS - 1

ER -