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The effects of LPS plus pro-inflammatory cytokines on glycogen synthesis in C2C12 myocytes

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posted on 2023-06-07, 15:45 authored by Francois-Xavier P.G. Roeseler de Rivera
Culturing C2C12 myoblasts and myotubes with a combination of LPS, TNF-a, IFN-? and IL1ß for 18 hours was used to determine the effects of endotoxic shock on possible causes of the dysregulation of glucose homeostasis associated with the syndrome. The in vitro model was confirmed by the significant production of NO in both myoblasts and myotubes following treatment. The treatment resulted in significantly different results between both myocyte preparations with regards to the regulation of glycogen synthesis. In the myoblasts, the treatment significantly increased myoblast glycogen synthesis, in a NO-independent manner, as seen by the inclusion of the NO synthase inhibitor L-NAME. This stimulation was unlikely to be due to a change in either GS or Phosphorylase activity. However it may have been caused by a significant increase in glucose transport induced by the treatment. This latter increase was also NO-independent, as well as not requiring reactive oxygen species. Insulin-induced myoblast protein synthesis was impaired by the treatment, which is likely due to an impairment of insulin-stimulated ERK1/2 phosphorylation. In the myotubes the case was different, as the treatment significantly reduced glycogen synthesis in a NO-dependent manner. This correlated with a NO-dependent increase in GS phosphorylation, indicating it was less active, however measurements of GS fractional activity failed to confirm this. Insulin stimulation of myotube glycogen synthesis was impaired by the treatment in a NO-independent manner, which may have involved an impairment of the insulin signal to ERK1/2. However the latter impairment was NO-dependent, suggesting other contributory mechanisms. Endotoxic treatment significantly increased myoblast protein content, but failed to do so in myotubes. This effect in the myoblasts may be explained by a significant increase in protein synthesis between 6 and 12 hours of treatment. None of the effects observed in the study were due to the treatment compromising cell viability.


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