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

• Published in: The Journal of biological chemistry 1999-08, Vol.274 (32), p.22139-22142
• Main Authors: Etgen, G J, Valasek, K M, Broderick, C L, Miller, A R
• Format: Article
• Language: English
• Subjects: Adenoviridae - genetics; Adenovirus; Animals; Biological Transport - drug effects; Deoxyglucose - metabolism; Female; Gene Transfer Techniques; Genetic Vectors; Glucose - metabolism; Glucose Transporter Type 1; Glucose Transporter Type 4; Humans; Injections, Intramuscular; Insulin - pharmacology; Monosaccharide Transport Proteins - analysis; Muscle Fibers, Fast-Twitch - enzymology; Muscle Proteins; Muscle, Skeletal - drug effects; Muscle, Skeletal - enzymology; Protein Kinase C - genetics; Protein Kinase C - pharmacology; Rats; Rats, Zucker; Recombinant Proteins - pharmacology
• ISSN: 0021-9258
• DOI: 10.1074/jbc.274.32.22139

An in vivo adenoviral gene delivery system was utilized to assess the effect of overexpressing protein kinase C (PKC)-zeta on rat skeletal muscle glucose transport activity. Female lean Zucker rats were injected with adenoviral/human PKC-zeta (hPKC-zeta) and adenoviral/LacZ in opposing tibialis anterior muscles. One week subsequent to adenoviral/gene delivery rats were subjected to hind limb perfusion. The hPKC-zeta protein was expressed at the same level (fast-twitch white) or at approximately 80% of the level (fast-twitch red) of endogenous PKC-zeta, thus approximately doubling the amount of PKC-zeta in tibialis anterior. Basal glucose transport activity was elevated approximately 3.4- and 2-fold, respectively, in fast-twitch white and red hPKC-zeta muscle relative to control. Submaximal insulin-stimulated glucose transport activity, corrected for basal transport, was approximately 90 and 40% over control values, respectively, in fast-twitch white and red hPKC-zeta muscle. The enhancement of glucose transport activity in muscle expressing hPKC-zeta 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-zeta to adult rat skeletal muscle in vivo and also affirm a role for PKC-zeta in the regulation of glucose transport activity.