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This Article Full Text Full Text (PDF) All Versions of this Article: 286/5/E753    most recent 00155.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Fluckey, J. D. Articles by Dohm, G. L. Search for Related Content PubMed PubMed Citation Articles by Fluckey, J. D. Articles by Dohm, G. L.

Active involvement of PKC for insulin-mediated rates of muscle protein synthesis in Zucker rats

¹Departments of Geriatrics, and Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205; Departments of ²Exercise, and Sport Science, and ³Physiology, East Carolina University, Greenville 27858; and ⁴Department of Medicine-Cardiology, Duke University, Durham, North Carolina 27710

Submitted 9 April 2003 ; accepted in final form 17 December 2003

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 whether 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) compared with no insulin, but overall activity was greater in obese animals (by 27% compared with lean, P < 0.05). To determine whether PKC plays a role in muscle protein synthesis, hindlimbs (n = 6–8 for each phenotype) were bilaterally perfused with or without insulin and/or GF-109203X (GF; 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 plus insulin resulted in elevated rates of protein synthesis in both phenotypes that were similar to rates of 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.

protein kinase C; obesity; bilateral hindlimb perfusion; gastrocnemius; phorbol esters