okadaic-acid has been researched along with 4-bromocrotonic-acid* in 1 studies
1 other study(ies) available for okadaic-acid and 4-bromocrotonic-acid
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Mechanism of inhibition of insulin-stimulated glucose transport by 4-bromocrotonic acid in 3T3-L1 adipocytes.
We have demonstrated previously that 4-bromocrotonic acid (Br-C4) inhibited insulin-stimulated glucose transport by interfering with GLUT4 translocation. In the present study, we further examined the underlying mechanism involved. Since insulin-induced insulin receptor substrate-1-associated phosphatidylinositol (PI) 3-kinase activity was not altered by Br-C4, we determined and found insulin activation of protein kinase B (PKB) and protein kinase Clambda (PKClambda) were both inhibited. However, time-course studies showed that only the inhibition of PKB activation correlated with the inhibition of insulin-stimulated glucose transport. In concert, insulin-stimulated Ser(473/474) phosphorylation on PKB(alpha/beta) were similarly decreased by Br-C4. The finding that okadaic acid-stimulated glucose transport and PKClambda activity were both inhibited by Br-C4 suggested that the effect of Br-C4 on Ser(473/474) phosphorylation was not mediated by protein phosphatase 2A. Moreover, whereas Br-C4 nearly abolished insulin-stimulated integrin-linked kinase (ILK) activity, it only inhibited insulin-stimulated PKB activity by 20%, implying that ILK was not the major kinase for Ser(473/474) phosphorylation. Taken together, these results support the notion that PKB is involved in insulin-stimulated glucose transport. In addition, Br-C4 seems to inhibit insulin-stimulated glucose transport via inhibiting insulin activation of PKB, probably by interfering with insulin activation of an upstream kinase responsible for the phosphorylation of Ser(473/474) residue. Topics: 3T3 Cells; Adipocytes; Animals; Biological Transport; Crotonates; Glucose; Hypoglycemic Agents; Insulin; Insulin Receptor Substrate Proteins; Ionophores; Isoenzymes; Mice; Okadaic Acid; Phosphatidylinositol 3-Kinases; Phosphoproteins; Phosphorylation; Protein Kinase C; Protein Kinase C beta; Protein Kinase C-alpha; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Tyrosine | 2003 |