TY - JOUR

T1 - Regulation of Dishevelled and β-catenin in rat skeletal muscle

T2 - An alternative exercise-induced GSK-3β signaling pathway

AU - Aschenbach, William G.

AU - Ho, Richard C.

AU - Sakamoto, Kei

AU - Fujii, Nobuharu

AU - Li, Yangfeng

AU - Kim, Young Bum

AU - Hirshman, Michael F.

AU - Goodyear, Laurie J.

PY - 2006/7/17

Y1 - 2006/7/17

N2 - β-catenin is a multifunctional protein involved in cell-cell adhesion and the Wnt signaling pathway. β-Catenin is activated upon its dephosphorylation, an event triggered by Dishevelled (Dvl)-mediated phosphorylation and deactivation of glycogen synthase kinase-3β (GSK-3β). In skeletal muscle, both insulin and exercise decrease GSK-3β activity, and we tested the hypothesis that these two stimuli regulate β-catenin. Immunoblotting demonstrated that Dvl, Axin, GSK-3β, and β-catenin proteins are expressed in rat red and white gastrocnemius muscles. Treadmill running exercise in vivo significantly decreased β-catenin phosphorylation in both muscle types, with complete dephosphorylation being elicited by maximal exercise. β-Catenin dephosphorylation was intensity dependent, as dephosphorylation was highly correlated with muscle glycogen depletion during exercise (r2 = 0.84, P < 0.001). β-Catenin dephosphorylation was accompanied by increases in GSK-3β Ser9 phosphorylation and Dvl-GSK-3β association. In contrast to exercise, maximal insulin treatment (1 U/kg body wt) had no effect on skeletal muscle β-catenin phosphorylation or Dvl-GSK-3β interaction. In conclusion, exercise in vivo, but not insulin, increases the association between Dvl and GSK-3β in skeletal muscle, an event paralleled by β-catenin dephosphorylation.

AB - β-catenin is a multifunctional protein involved in cell-cell adhesion and the Wnt signaling pathway. β-Catenin is activated upon its dephosphorylation, an event triggered by Dishevelled (Dvl)-mediated phosphorylation and deactivation of glycogen synthase kinase-3β (GSK-3β). In skeletal muscle, both insulin and exercise decrease GSK-3β activity, and we tested the hypothesis that these two stimuli regulate β-catenin. Immunoblotting demonstrated that Dvl, Axin, GSK-3β, and β-catenin proteins are expressed in rat red and white gastrocnemius muscles. Treadmill running exercise in vivo significantly decreased β-catenin phosphorylation in both muscle types, with complete dephosphorylation being elicited by maximal exercise. β-Catenin dephosphorylation was intensity dependent, as dephosphorylation was highly correlated with muscle glycogen depletion during exercise (r2 = 0.84, P < 0.001). β-Catenin dephosphorylation was accompanied by increases in GSK-3β Ser9 phosphorylation and Dvl-GSK-3β association. In contrast to exercise, maximal insulin treatment (1 U/kg body wt) had no effect on skeletal muscle β-catenin phosphorylation or Dvl-GSK-3β interaction. In conclusion, exercise in vivo, but not insulin, increases the association between Dvl and GSK-3β in skeletal muscle, an event paralleled by β-catenin dephosphorylation.

KW - Akt

KW - Glycogen-synthase kinase-3β

KW - Insulin

KW - Protein kinase C

KW - Wnt

UR - http://www.scopus.com/inward/record.url?scp=33745857968&partnerID=8YFLogxK

U2 - 10.1152/ajpendo.00180.2005

DO - 10.1152/ajpendo.00180.2005

M3 - Journal article

C2 - 16478782

AN - SCOPUS:33745857968

VL - 291

SP - E152-E158

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

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

SN - 1522-1555

IS - 1

ER -