Surgery-induced insulin resistance in human patients: relation to glucose transport and utilization

To investigate the underlying molecular mechanisms for surgery-induced insu lin resistance in skeletal muscle, six otherwise healthy patients undergoin g total hip replacement were studied before, during, and after surgery. Pat ients were studied under basal conditions and during physiological hyperins ulinemia (60 mu U/ml). Biopsies of vastus lateralis muscle were used to mea sure GLUT-4 translocation, glucose transport, and glycogen synthase activit ies. Surgery reduced insulin-stimulated glucose disposal (P < 0.05) without altering the insulin-stimulated increase in glucose oxidation or suppressi on of endogenous glucose production. Preoperatively, insulin infusion incre ased plasma membrane GLUT-4 in all six subjects (P < 0.05), whereas insulin -stimulated GLUT-4 translocation only occurred in three patients postoperat ively (not significant). Moreover, nonoxidative glucose disposal rates and basal levels of glycogen synthase activities in muscle were reduced postope ratively (P ( 0.05). These findings demonstrate that peripheral insulin res istance develops immediately postoperatively and that this condition might be associated with perturbations in insulin-stimulated GLUT-4 translocation as well as nonoxidative glucose disposal, presumably at the level of glyco gen synthesis.