Regulation of GLUT1-mediated glucose uptake by PKCλ–PKCβ_II interactions in 3T3-L1 adipocytes

Members of the PKC (protein kinase C) superfamily play key regulatory roles in glucose transport. How the different PKC isotypes are involved in the regulation of glucose transport is still poorly defined. PMA is a potent activator of conventional and novel PKCs and PMA increases the rate of glucose uptake in many different cell systems. In the present study, we show that PMA treatment increases glucose uptake in 3T3-L1 adipocytes by two mechanisms: a mitogen-activated protein kinase kinase-dependent increase in GLUT1 (glucose transporter 1) expression levels and a PKCλ-dependent translocation of GLUT1 towards the plasma membrane. Intriguingly, PKCλ co-immunoprecipitated with PKCβ_II and did not with PKCβ_I. Previously, we have described that down-regulation of PKCβ_II protein levels or inhibiting PKCβ_II by means of the myristoylated PKCβC2–4 peptide inhibitor induced GLUT1 translocation towards the plasma membrane in 3T3-L1 adipocytes. Combined with the present findings, these results suggest that the liberation of PKCλ from PKCβ_II is an important factor in the regulation of GLUT1 distribution in 3T3-L1 adipocytes.