Protein Kinase C (PKC)-a Activation Inhibits PKC-z and Mediates the Action of PED/PEA-15 on Glucose Transport in the L6 Skeletal Muscle Cells

Overexpression of the PED/PEA-15 protein in muscle and adipose cells increases glucose transport and im-pairs further insulin induction. Like glucose transport, protein kinase C (PKC)-a and-b are also constitutively activated and are not further stimulatable by insulin in L6 skeletal muscle cells overexpressing PED (L6PED). PKC-z features no basal change but completely loses insulin sensitivity in L6PED. In these cells, blockage of PKC-a and-b additively returns 2-deoxy-D-glucose (2-DG) uptake to the levels of cells expressing only endog-enous PED (L6WT). Blockage of PKC-a and-b also restores insulin activation of PKC-z in L6PED cells, with that of PKC-a sixfold more effective than PKC-b. Simi-lar effects on 2-DG uptake and PKC-z were also achieved by 50-fold overexpression of PKC-z in L6PED. In L6WT