Submitted on April 9, 2003
Accepted on December 17, 2003
Active involvement of PKC for insulin mediated rates of muscle protein synthesis in Zucker rats
James D. Fluckey1*, Ronald N. Cortright2, Edward Tapscott3, Timothy Koves3, Latasha Smith1, Steven Pohnert4, and G. Lynis Dohm5
1 Departments of Geriatrics, and Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
2 Department of Exercise and Sport Science, East Carolina University, Greenville, NC, USA; Department of Physiology, East Carolina University, Greenville, NC, USA
3 Department of Exercise and Sport Science, East Carolina University, Greenville, NC, USA
4 Department of Medicine-Cardiology, Duke University, Durham, NC, USA
5 Department of Physiology, East Carolina University, Greenville, NC, USA
* To whom correspondence should be addressed. E-mail: fluckeyjamesd{at}uams.edu.
A recent report from our group demonstrated that insulin facilitates
muscle protein synthesis in obese Zucker rats. The purpose of this study was to
determine if protein kinase C (PKC), a probable modulator of insulin signal transduction
and/or mRNA translation, has a role in this insulin-mediated anabolic response. In the
first portion of the study, gastrocnemius muscles of lean and obese Zucker rats (n=5-7 for
each phenotype) were bilaterally perfused with or without insulin to assess cytosolic and
membrane PKC activity. Limbs perfused with insulin demonstrated greater PKC activity
in both lean and obese Zucker rats (p<0.05) when compared to no insulin, but overall
activity was greater in obese animals (by ~27% compared to lean; p<0.05). To determine
if PKC plays a role in muscle protein synthesis, hindlimbs (n=6-8 for each phenotype)
were bilaterally perfused with or without insulin and/or GF109203X (a PKC inhibitor).
The presence of GF did not influence the rates of insulin mediated protein synthesis in
gastrocnemius muscle of lean Zucker rats. However, when obese rats were perfused with
GF (p<0.05) the effect of insulin on elevating rates of protein synthesis was not observed.
We also used phorbol 12-myristate 13-acetate (TPA, a PKC activator; n=5-7 for each
phenotype) with and without insulin to determine the effect of PKC activation on muscle
protein synthesis. TPA alone did not elevate muscle protein synthesis in lean or obese
rats. However, TPA + insulin resulted in elevated rates of protein synthesis in both
phenotypes that was similar to insulin alone of obese rats. These results suggest that
PKC is a modulator, and is necessary but not sufficient for insulin-mediated, protein
anabolic responses in skeletal muscle.
