OKADAIC ACID, VANADATE, AND PHENYLARSINE OXIDE STIMULATE 2-DEOXYGLUCOSE TRANSPORT IN INSULIN-RESISTANT HUMAN SKELETAL-MUSCLE

In response to insulin, several proteins are phosphorylated on tyrosin e and on serine/threonine residues, Decreased phosphorylation of signa ling peptides by a defective insulin receptor kinase may be a cause of insulin resistance, Accordingly, inhibition of the appropriate phosph atases might increase the phosphorylation state of these signaling pep tides and thereby elicit increased glucose transport, The purpose of t his study was to examine the effect of the serine/threonine phosphatas e inhibitor okadaic acid and the tyrosine phosphatase inhibitors pheny larsine oxide and vanadate on 2-deoxyglucose transport in insulin-resi stant human skeletal muscle, Ad three phosphatase inhibitors stimulate d 2-deoxyglucose transport in insulin-resistant skeletal muscle, These data suggest that these compounds have bypassed a defect in at least one of the signaling pathways leading to glucose transport, Furthermor e, maximal transport rates induced by the simultaneous presence of ins ulin and phosphatase inhibitor in insulin-resistant muscle were equal to insulin-stimulated rates in lean control subjects. However, both va nadate alone and vanadate plus insulin stimulated 2-deoxyglucose trans port significantly more in insulin-sensitive tissue than in insulin-re sistant tissue, These results demonstrate that although vanadate is ab le to stimulate glucose transport in insulin-resistant muscle, it is n ot able to normalize transport to the same rate achieved in insulin-se nsitive muscle.