OKADAIC ACID EXERTS A FULL INSULIN-LIKE EFFECT ON GLUCOSE-TRANSPORT AND GLUCOSE-TRANSPORTER-4 TRANSLOCATION IN HUMAN ADIPOCYTES - EVIDENCE FOR A PHOSPHATIDYLINOSITOL 3-KINASE-INDEPENDENT PATHWAY

The effects of the serine/threonine phosphatase inhibitor, okadaic aci d, and insulin on glucose transport activity, glucose transporter 4 tr anslocation to the plasma membrane, and the signaling pathway of insul in were examined in human adipocytes, Okadaic acid consistently produc ed a greater increase than insulin in the rate of glucose transport, a nd both agents together had a partial additive effect, Both insulin al one and okadaic acid alone stimulated the translocation of glucose tra nsporter 4 to the plasma membrane, Insulin, but not okadaic acid, stim ulated phosphatidylinositol 3-kinase (PI 3-kinase) activity, and wortm annin completely inhibited the effect of insulin on glucose transport, When the cells were incubated with both agents, okadaic acid inhibite d insulin-stimulated PI 3-kinase activity but did not block the associ ation of the p85 or p110 subunits of PI 3-kinase with insulin receptor substrate 1, Insulin-stimulated tyrosine phosphorylation of insulin r eceptor substrate 1 was only slightly reduced (15-30%) by okadaic acid , These data demonstrate that okadaic acid exerts a full insulin-like effect independent of the activation of PI 3-kinase. Thus, PI 3-kinase lipid kinase is not essential for glucose transporter 4 translocation in human adipocytes, and different pathways exist that lead to glucos e transporter 4 translocation and increased glucose transport.