Glucocorticoid-induced insulin resistance of protein synthesis is independent of the rapamycin-sensitive pathways in rat 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 pathways in the insulin resistance of muscle protein synthesis observed during glucocorticoid treatment. Dexamethasone treatment decreased the effect of insulin on protein synthesis (-35. 2%) in epitrochlearis muscle incubated in vitro. This resistance is associated with a total blockage of the stimulation of p70(S6K) by insulin without any significant decrease in the amount of the kinase. However, the effect of rapamycin (inhibitor of several intracellular pathways including p70(S6K) pathways) on muscle protein synthesis was not modified by dexamethasone in rat muscles. This suggested that 'rapamycin-sensitive pathways' associated with the insulin stimulation of protein synthesis were not altered by glucocorticoids and thus are not responsible for the insulin resistance observed. As incubation of muscles with a MAP kinase inhibitor (PD98059) did not modify the stimulation of protein synthesis by insulin and as glucocorticoids did not alter the effect of insulin on p90(RSK )activity, our results provide evidence that glucocorticoid-induced alterations in muscle protein synthesis regulation by insulin do not involve factors or kinases that are dependent on MAP kinase and/or p90(RSK).
Dardevet
D
D
Unité d'Etude du Métabolisme Azoté, Institut National de la Recherche Agronomique, 63122 Ceyrat, France.
Sornet
C
C
Grizard
J
J
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis*; D003907:Dexamethasone / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D018482:Muscle, Skeletal; D051381:Rats; D017207:Rats, Sprague-Dawley; D019893:Ribosomal Protein S6 Kinases / Q000096:biosynthesis*; D020123:Sirolimus / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D005419:Flavonoids; D005938:Glucocorticoids; D003907:Dexamethasone; D019893:Ribosomal Protein S6 Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D020123:Sirolimus