Abstract
BackgroundFatty acid-induced insulin resistance and impaired glucose uptake activity in muscle cells are fundamental events in the development of type 2 diabetes and hyperglycemia. There is an increasing demand for compounds including drugs and functional foods that can prevent myocellular insulin resistance.MethodsIn this study, we established a high-throughput assay to screen for compounds that can improve myocellular insulin resistance, which was based on a previously reported non-radioisotope 2-deoxyglucose (2DG) uptake assay. Insulin-resistant muscle cells were prepared by treating rat L6 skeletal muscle cells with 750 μM palmitic acid for 14 h. Using the established assay, the impacts of several fatty acids on myocellular insulin resistance were determined.ResultsIn normal L6 cells, treatment with saturated palmitic or stearic acid alone decreased 2DG uptake, whereas unsaturated fatty acids did not. Moreover, co-treatment with oleic acid canceled the palmitic acid-induced decrease in 2DG uptake activity. Using the developed assay with palmitic acid-induced insulin-resistant L6 cells, we determined the effects of other unsaturated fatty acids. We found that arachidonic, eicosapentaenoic and docosahexaenoic acids improved palmitic acid-decreased 2DG uptake at lower concentrations than the other unsaturated fatty acids, including oleic acid, as 10 μM arachidonic acid showed similar effects to 750 μM oleic acid.ConclusionsWe have found that polyunsaturated fatty acids, in particular arachidonic and eicosapentaenoic acids prevent palmitic acid-induced myocellular insulin resistance.
Highlights
Fatty acid-induced insulin resistance and impaired glucose uptake activity in muscle cells are fundamental events in the development of type 2 diabetes and hyperglycemia
Determination of optimum treatment time and concentration of palmitic acid To induce insulin resistance in muscle cells, we treated differentiated L6 skeletal muscle cells with palmitic acid according to a method reported by Chaves et al [7]
After we confirmed that palmitic acid did not show significant cytotoxicity by 900 μM, the treatment concentration was fixed at 750 μM according to the previous reports [4,6] (Figure 1B)
Summary
Fatty acid-induced insulin resistance and impaired glucose uptake activity in muscle cells are fundamental events in the development of type 2 diabetes and hyperglycemia. There is an increasing demand for compounds including drugs and functional foods that can prevent myocellular insulin resistance. Several unsaturated fatty acids, including palmitoleic and oleic acids, were reported to ameliorate palmitic acid-induced insulin resistance in myotubes [4,12,13]. Chen et al have reported that berberine, an isoquinoline alkaloid, improves palmitic acid-induced insulin resistance in L6 myotubes by inhibiting peroxisome proliferator-activated receptor (PPAR)-g [14]. Other than these compounds, little is known about inhibitors of palmitic acid-induced insulin resistance in muscle cells
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