Reversal of chronic alterations of skeletal muscle protein kinase c
from fat-fed rats by brl 49653..
Schmitz-Peiffer, Carsten, Nicholas D. Oakes, Carol L. Browne, Edward
W. Kraegen, and Trevor J. Biden.
Garvan Institute of Medical Research, Sydney, NSW 2010,
Australia.
APStracts 4:0170E, 1997.
We have recently shown that the reduction in insulin sensitivity of
rats fed a high-fat diet is associated with the translocation of the
novel protein kinase C e (nPKC e) from cytosolic to particulate
fractions in red skeletal muscle and also the down-regulation of
cytosolic nPKC q. Here we have further investigated the link between
insulin resistance and PKC by assessing the effects of the
thiazolidinedione insulin-sensitiser BRL 49653 on PKC isoenzymes in
muscle. BRL 49653 increased the recovery of nPKC isoenzymes in
cytosolic fractions of red muscle from fat-fed rats, reducing their
apparent activation and/or down-regulation, while PKC in control rats
was unaffected. Since BRL 49653 also improves insulin-stimulated
glucose uptake in fat-fed rats, and reduces muscle lipid storage,
especially diglyceride content, these results strengthen the
association between lipid availability, nPKC activation and skeletal
muscle insulin resistance, and support the hypothesis that chronic
activation of nPKC isoenzymes is involved in the generation of muscle
insulin resistance in fat-fed rats.
Received 23 May 1997; accepted in final form 23 July 1997.
APS Manuscript Number E234-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 27 August 1997