Acute impairment of insulin signalling by dexamethasone in primary cultured rat skeletal myocytes.
In this study, we examined the cellular content of the insulin receptor substrate (IRS)-1, the levels of phosphorylated tyrosine (pY) and serine (pS) residues in IRS-1, and the glucose transporters GLUT-1 and GLUT-4 in primary cultured rat skeletal myocytes treated with the glucocorticoid, dexamethasone. Dexamethasone markedly increased basal and insulin-stimulated IRS-1 content 4 to 5-fold (p < 0.01). A similar level of increase was observed for IRS-1 pY content. However, dexamethasone treatment had no effect on IRS-1 pS content. Further, dexamethasone reduced the cellular content of GLUT-1 when insulin and glucose were absent (p < 0.05), but did not significantly affect the expression of GLUT-4 in the presence of insulin (p > 0.05). We conclude that dexamethasone treatment impairs insulin signalling by a mechanism independent of serine-phosphorylation-mediated IRS-1 depletion, or of impairment of GLUT-1 expression. Instead, dexamethasone-induced insulin resistance may be mediated via reduced cellular content of IRS-1 accompanied by parallel reduction in tyrosine phosphorylation in IRS-1.
Brown
Paul D
PD
Department of Basic Medical Sciences (Biochemistry section), University of the West Indies, Kingston, Jamaica. paul.brown@uwimona.edu.jm
Badal
Simone
S
Morrison
Seian
S
Ragoobirsingh
Dalip
D
D000818:Animals; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000187:drug effects*; D010750:Phosphoproteins / Q000378:metabolism; D010768:Phosphoserine / Q000378:metabolism; D019000:Phosphotyrosine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*
D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D010750:Phosphoproteins; D010768:Phosphoserine; D019000:Phosphotyrosine; D003907:Dexamethasone