title: In vivo adenoviral delivery of recombinant human protein kinase C-zeta 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)-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.
authors.affiliation: Diabetes Research, Endocrine Division, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA. Etgen_Garret_J@Lilly.com
authors.forename: G J
authors.initials: GJ
authors.lastname: Etgen
authors.forename: K M
authors.initials: KM
authors.lastname: Valasek
authors.forename: C L
authors.initials: CL
authors.lastname: Broderick
authors.forename: A R
authors.initials: AR
authors.lastname: Miller
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003847:Deoxyglucose / Q000378:metabolism; D005260:Female; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D006801:Humans; D007273:Injections, Intramuscular; D007328:Insulin / Q000494:pharmacology; D009004:Monosaccharide Transport Proteins / Q000032:analysis; D018656:Muscle Fibers, Fast-Twitch / Q000201:enzymology; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology; D011493:Protein Kinase C / Q000235:genetics / Q000494:pharmacology*; D051381:Rats; D011924:Rats, Zucker; D011994:Recombinant Proteins / Q000494:pharmacology; D000099221:Protein Kinase C zeta
chemical_list: D003847:Deoxyglucose; D005947:Glucose; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D011493:Protein Kinase C; D011994:Recombinant Proteins; D000099221:Protein Kinase C zeta; C495677:SLC2A1 protein, human; C495692:SLC2A4 protein, human; C495679:Slc2a1 protein, rat; C495694:Slc2a4 protein, rat