Received for publication June 25, 2004.
Revised October 19, 2004.
Accepted for publication October 19, 2004.

Protein Kinase C-Independent Effects of Protein Kinase D3 in Glucose Transport in L6 Myotubes

Abstract

Protein kinase C (PKC) and protein kinase D (PKD) coordinate and regulate many fundamental cellular processes. In this study, we evaluate the role of classical and novel PKCs (c/nPKC) and PKD in glucose transport in L6 myotubes. c/nPKC is either activated by short-term PMA treatment or down-regulated by prolonged PMA treatment at high dose in L6 myotubes. Our results indicate that PMA treatments have little impact on basal and insulin- stimulated glucose uptake and on insulin-induced Akt activation. In contrast, the PKC inhibitors Go6976, Go6983, GF 109203X, and Ro 31-8220 block basal and insulin-stimulated glucose uptake, and their inhibitory effects persist upon down-regulation of c/nPKC by PMA, implying the presence of PKC-independent effecters in mediating their inhibition of glucose uptake. Go6976, the potent cPKC inhibitor that also effectively inhibits PKD, dose-dependently blocks basal glucose uptake in L6 myotubes, while Go6983, the non-selective PKC inhibitor that is ineffective for PKD, has little effect on basal glucose uptake, implying the involvement of PKD in this process. Most prominently, adenoviral gene expression of a dominant-negative PKD isoform PKD3 inhibits primarily basal glucose uptake and, to a small extent, insulin-stimulated glucose uptake, while overexpression of wild-type PKD3 significantly enhances basal glucose uptake. Moreover, expression of a PKD3-targeted siRNA significantly inhibits basal glucose uptake. Taken together, our results indicate that PKD, specifically PKD3, directly contributes to insulin-independent basal glucose uptake in L6 skeletal muscle cells.

Key words: Insulin, Protein Kinase C, Protein Kinases (other)

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