Mediation of protein kinase C zeta in μ-opioid receptor activation for increase of glucose uptake into cultured myoblast C2C12 cells

The present study is designed to investigate the role of atypical protein kinase C (PKC) in the signaling of μ-opioid receptors (MOR) for glucose uptake in myoblast C2C12 cells. Loperamide enhanced the uptake of radioactive deoxyglucose into C2C12 cells in a concentration-dependent manner that was abolished in cells pre-incubated with GF109203X at concentrations sufficient to block PKC. Inhibition of the atypical zeta (ζ) isoform of PKC using myristoylated PKC pseudosubstrate resulted in a concentration-dependent decrease of loperamide-stimulated glucose uptake into C2C12 cells. In addition, loperamide elicited the phosphorylation of PKC-ζ in C2C12 cells in a concentration-dependent manner that was abolished by pretreatment with naloxonazine at concentrations sufficient to block MOR. These results suggest the mediation of PKC-ζ in MOR signaling for glucose uptake in C2C12 cells. Activation of PKC-ζ by MOR stimulation is highly relevant to the search for therapeutic targets for glucose transport in insulin-sensitive tissues.