title: Active involvement of PKC for insulin-mediated rates of muscle protein synthesis in Zucker rats.
abstract: 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 approximately 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.
authors.affiliation: Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA. fluckeyjamesd@uams.edu
authors.forename: James D
authors.initials: JD
authors.lastname: Fluckey
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Cortright
authors.forename: Edward
authors.initials: E
authors.lastname: Tapscott
authors.forename: Timothy
authors.initials: T
authors.lastname: Koves
authors.forename: Latasha
authors.initials: L
authors.lastname: Smith
authors.forename: Steven
authors.initials: S
authors.lastname: Pohnert
authors.forename: G Lynis
authors.initials: GL
authors.lastname: Dohm
mesh_terms: D000818:Animals; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007328:Insulin / Q000502:physiology*; D008301:Maleimides / Q000494:pharmacology; D009124:Muscle Proteins / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D011924:Rats, Zucker
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D007328:Insulin; D008301:Maleimides; D009124:Muscle Proteins; D011493:Protein Kinase C; C070515:bisindolylmaleimide I