Okadaic acid inhibits insulin‐induced glucose transport in fetal brown adipocytes in an Akt‐independent and protein kinase C ζ‐dependent manner

FEBS Letters

Lorenzo, Margarita¹  Valverde, Angela M.¹  Navarro, Paloma¹  Mur, Cecilia¹  Benito, Manuel¹ 

[1] Departamento de Bioquı́mica y Biologı́a Molecular, Centro Mixto CSIC/UCM, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain

关键词: Insulin signaling;    Okadaic acid;    Serine/threonine phosphorylation;    Insulin receptor substrate;    Glucose transport;    Protein kinase C ζ;    Insulin resistance;    IRS;    insulin receptor substrate;    PI;    phosphatidylinositol;    FCS;    fetal calf serum;    PBS;    phosphate buffered saline;   

DOI  :  10.1016/S0014-5793(00)01448-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

In the present study we have investigated the effect of increased serine/threonine phosphorylation of insulin receptor substrates-1 and -2 (IRS-1 and IRS-2) by okadaic acid pretreatment on brown adipocyte insulin signalling leading to glucose transport, an important metabolic effect of insulin in brown adipose tissue. Okadaic acid pretreatment before insulin stimulation decreased IRS-1 and IRS-2 tyrosine phosphorylation in parallel to a decrease in their sodium dodecyl sulfate–polyacrylamide gel electrophoresis mobility. IRS-1/IRS-2-associated p85α and phosphatidylinositol (PI) 3-kinase enzymatic activity were partly reduced in brown adipocytes pretreated with okadaic acid upon stimulation with insulin. Furthermore, insulin-induced glucose uptake was totally abolished by the inhibitor in parallel with a total inhibition of insulin-induced protein kinase C (PKC) ζ activity. However, activation of Akt/PKB or p70 S6 kinase (p70^s6k) by insulin remained unaltered. Our results suggest that downstream of PI 3-kinase, insulin signalling diverges into at least two independent pathways through Akt/PKB and PKC ζ, the PKC ζ pathway contributing to glucose transport induced by insulin in fetal brown adipocytes.

【 授权许可】

Unknown