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Ascorbate Rescues Peroxide Induced Insulin Resistance in Skeletal Muscle
Author(s) -
Eccardt Amanda,
Mattathil Lyn,
Bell Thomas,
Patel Rishi,
Mannino Mark,
Fisher Jonathan
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.618.27
Subject(s) - insulin resistance , reactive oxygen species , chemistry , protein kinase b , oxidative stress , insulin , antioxidant , myogenesis , biochemistry , nadph oxidase , glucose uptake , peroxidase , medicine , endocrinology , biology , phosphorylation , enzyme , in vitro
Ascorbate plays a key antioxidant role in protection of cells from damage by reactive oxygen species, which have been implicated in causing metabolic dysfunction such as diabetes. Thus, we hypothesized that ascorbate could aid in rescue from insulin resistance brought on by exposure to reactive oxygen species. In addition, we hypothesized that the peroxidase mimetic Fe(III)tetrakis(4‐benzoic acid)porphyrin (FeTBAP) could act synergistically with ascorbate in defense against oxidative stress. In order to measure the protective effect of ascorbate, we pretreated C2C12 myotubes with ascorbate. We then exposed the myotubes to glucose oxidase (GO), an enzyme that utilizes glucose to produce hydrogen peroxide, thus mimicking a state of oxidative stress prior to exposure to insulin. Data were quantified via western blot analysis monitoring phosphorylated AKT and total AKT. In order to assay the ability of FeTBAP in conjunction with ascorbate to protect against insulin resistance, C2C12 myotubes and isolated soleus were first pretreated with ascorbate and FeTBAP and then exposed to glucose oxidase followed by insulin. We found that ascorbate rescues insulin resistance brought on by exposure to reactive oxygen species. In addition, preliminary data from C2C12 myotubes and soleus illustrated a trend in which FeTBAP in combination with ascorbate protected against insulin resistance. Taken together, these data demonstrate a functional role of ascorbate in which the antioxidant on its own and in conjunction with FeTBAP rescues cells from peroxide induced insulin resistance. Support or Funding Information This project was supported by United States Public Health Service award R15DK102122 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .