title: 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.
abstract: The effects of the serine/threonine phosphatase inhibitor, okadaic acid, and insulin on glucose transport activity, glucose transporter 4 translocation to the plasma membrane, and the signaling pathway of insulin were examined in human adipocytes. Okadaic acid consistently produced a greater increase than insulin in the rate of glucose transport, and both agents together had a partial additive effect. Both insulin alone and okadaic acid alone stimulated the translocation of glucose transporter 4 to the plasma membrane. Insulin, but not okadaic acid, stimulated phosphatidylinositol 3-kinase (PI 3-kinase) activity, and wortmannin completely inhibited the effect of insulin on glucose transport. When the cells were incubated with both agents, okadaic acid inhibited insulin-stimulated PI 3-kinase activity but did not block the association of the p85 or p110 subunits of PI 3-kinase with insulin receptor substrate 1. Insulin-stimulated tyrosine phosphorylation of insulin receptor 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 glucose transporter 4 translocation and increased glucose transport.
authors.affiliation: Lundberg Laboratory for Diabetes Research, Department of Internal Medicine, Sahlgrenska University Hospital, University of Goteborg, S-413 45 Goteborg, Sweden.
authors.forename: C M
authors.initials: CM
authors.lastname: Rondinone
authors.forename: U
authors.initials: U
authors.lastname: Smith
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000595:Amino Acid Sequence; D001692:Biological Transport / Q000187:drug effects; D002451:Cell Compartmentation / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D004347:Drug Interactions; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D019319:Okadaic Acid; D019869:Phosphatidylinositol 3-Kinases; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D004988:Ethers, Cyclic; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; C526292:IRS1 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D010750:Phosphoproteins; C495692:SLC2A4 protein, human; D019319:Okadaic Acid; D014443:Tyrosine; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D010749:Phosphoprotein Phosphatases; D005947:Glucose