Modulation of the caveolin-3 and Akt status in caveolae by insulin resistance in H9c2 cardiomyoblasts.
We investigated glucose uptake and the translocation of Akt and caveolin-3 in response to insulin in H9c2 cardiomyoblasts exposed to an experimental insulin resistance condition of 100 nM insulin in a 25 mM glucose containing media for 24 h. The cells under the insulin resistance condition exhibited a decrease in insulin-stimulated 2-deoxy[(3)H]glucose uptake as compared to control cells grown in 5 mM glucose media. In addition to a reduction in insulin-induced Akt translocation to membranes, we observed a significant decrease in insulin-stimulated membrane association of phosphorylated Akt with a consequent increase of the cytosolic pool. Actin remodeling in response to insulin was also greatly retarded in the cells. When translocation of Akt and caveolin-3 to caveolae was examined, the insulin resistance condition attenuated localization of Akt and caveolin-3 to caveolae from cytosol. As a result, insulin-stimulated Akt activation in caveolae was significantly decreased. Taken together, our data indicate that the decrease of glucose uptake into the cells is related to their reduced levels of caveolin-3, Akt and phosphorylated Akt in caveolae. We conclude that the insulin resistance condition induced the retardation of their translocation to caveolae and in turn caused an attenuation in insulin signaling, namely activation of Akt in caveolae for glucose uptake into H9c2 cardiomyoblasts.
Department of Biochemistry, Division of Life Science, College of Natural Sciences, Graduate School of Applied Life Science, Gyeongsang National University, Jinju 660-701, Korea.
Hyunil
H
Ha
Yunbae
Y
Pak
D000818:Animals; D001692:Biological Transport; D021941:Caveolae / Q000187:drug effects / Q000378:metabolism*; D051244:Caveolin 3; D022461:Caveolins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D006321:Heart / Q000196:embryology; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats
C495549:Cav3 protein, rat; D051244:Caveolin 3; D022461:Caveolins; D007328:Insulin; D011518:Proto-Oncogene Proteins; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose