Glucocorticoid-induced insulin resistance of protein synthesis is independent of the rapamycin-sensitive pathways in vat skeletal muscle

This study was designed to evaluate the role of p70 S6 kinase (p70(S6K) ), p90 S6 kinase (p90(RSK)) and mitogen-activated protein (MAP) kinase pathway s in the insulin resistance of muscle protein synthesis observed during glu cocorticoid treatment. Dexamethasone treatment decreased the effect of insu lin on protein synthesis (-35.2%) in epitrochlearis muscle incubated in vit ro. This resistance is associated with a total blockage of the stimulation of p70(S6K) by insulin without any significant decrease in the amount of th e kinase. However, the effect of rapamycin (inhibitor of several intracellu lar pathways including p70(S6K) pathways) on muscle protein synthesis was n ot modified by dexamethasone in rat muscles. This suggested that 'rapamycin -sensitive pathways' associated with the insulin stimulation of protein syn thesis were not altered by glucocorticoids and thus are not responsible for the insulin resistance observed. As incubation of muscles with a MAP kinas e inhibitor (PD98059) did not modify the stimulation of protein synthesis b y insulin and as glucocorticoids did not alter the effect of insulin on p90 (RSK) activity, our results provide evidence that glucocorticoid-induced al terations in muscle protein synthesis regulation by insulin do not involve factors or kinases that are dependent on MAP kinase and/or p90(RSK)