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1 Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario N1G 2W1; 3 Department of Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada; and 2 Department of Biochemistry and Molecular Biology, Indiana University, School of Medicine, Indianapolis, Indiana 46202
Fiber type
specificity for expression of all three rat skeletal muscle pyruvate
dehydrogenase kinase (PDK) isoforms (PDK1, 2, and 4) was determined in
fed and 24-h fasted rats. PDK activity and isoform protein and mRNA
contents were determined in white gastrocnemius (WG; fast-twitch
glycolytic), red gastrocnemius (RG; fast-twitch oxidative), and soleus
(Sol; slow-twitch oxidative) muscles. PDK activity was lower in
WG compared with oxidative muscles (RG, Sol) in both fed and fasted
rats. PDK activities from fed muscles were 0.12 ± 0.04, 0.30 ± 0.01, and 0.36 ± 0.08 min
1 in WG, Sol,
and RG, respectively, and increased in fasted muscles (0.36 ± 0.09, 0.68 ± 0.18, and 0.80 ± 0.14 min
1).
This correlated with increased PDK4 protein and to a lesser extent with
PDK4 mRNA. PDK2 protein was not different between fiber types in fed or
fasted rats, but PDK2 mRNA content was twofold greater in RG from
fasted rats compared with fed rats. PDK1 was unaltered by fasting in
all muscle types at both the protein and mRNA level, but in both fed
and fasted rats had much greater protein and mRNA content in the
oxidative vs. glycolytic muscles. In conclusion, PDK activity and PDK1
and 4 protein and mRNA were lower in glycolytic vs. oxidative muscles
from fed and fasted rats. Fasting for 24 h induced a two- to
threefold increase in PDK activity that was mainly due to increases in
PDK4 protein and mRNA. PDK1 and 2 protein and mRNA were generally
unaltered by fasting in all fiber types, except for increased PDK2 mRNA
in the fast oxidative fibers. Because the PDK isoforms vary greatly in
their kinetic properties, their relative proportions in the three fiber
types at any given time during fasting could significantly alter the
acute regulation of the pyruvate dehydrogenase complex.
starvation; carbohydrate metabolism; oxidative fibers; glycolytic fibers; pyruvate dehydrogenase kinase isoform mRNA and protein; pyruvate dehydrogenase regulation
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