In vivo adenoviral delivery of recombinant human protein kinase C-ζ stimulates glucose transport activity in rat skeletal muscle

Abstract

An in vivo adenoviral gene delivery system was utilized to assess the effect of overexpressing protein kinase C (PKC)-ζ on rat skeletal muscle glucose transport activity. Female lean Zucker rats were injected with adenoviral/human PKC-ζ (hPKC-ζ) and adenoviral/LacZ in opposing tibialis anterior muscles. One week subsequent to adenoviral/gene delivery rats were subjected to hind limb perfusion. The hPKC-ζ protein was expressed at the same level (fast-twitch white) or at ~80% of the level (fast-twitch red) of endogenous PKC-ζ, thus approximately doubling the amount of PKC-ζ in tibialis anterior. Basal glucose transport activity was elevated ~3.4- and 2-fold, respectively, in fast-twitch white and red hPKC-ζ muscle relative to control. Submaximal insulin-stimulated glucose transport activity, corrected for basal transport, was ~90 and 40% over control values, respectively, in fast-twitch white and red hPKC-ζ muscle. The enhancement of glucose transport activity in muscle expressing hPKC-ζ occurred in the absence of any change in GLUT1 or GLUT4 protein levels, suggesting a redistribution of existing transporters to the cell surface. These results demonstrate that an adenoviral vector can be used to deliver expressible hPKC-ζ to adult rat skeletal muscle in vivo and also affirm a role for PKC-ζ in the regulation of glucose transport activity.