Skeletal muscle serves an important role in the utilization of glucose during insulin‑stimulated conditions. Excessive saturated fatty acids are considered to be a major contributing factor to insulin resistance in skeletal muscle cells. The present study investigated the effects of hispidin on palmitate‑induced insulin resistance in C2C12 skeletal muscle myotubes via an MTT assay, glucose uptake assay, Oil‑Red‑O staining and western blot analysis. Hispidin reversed the palmitate‑induced inhibition of glucose uptake, and inhibited palmitate‑induced intracellular lipid accumulation. Hispidin suppressed insulin receptor substrate‑1 Ser307 phosphorylation, and significantly promoted the activation of phosphatidylinositol‑3‑kinase and Akt, via inhibition of protein kinase C theta. Furthermore, hispidin treatment of C2C12 muscle cells increased glucose uptake via activation of adenosine monophosphate‑activated protein kinase. These findings indicated that hispidin may improve palmitate‑induced insulin resistance in skeletal muscle myotubes, and therefore hispidin treatment may be beneficial for patients with diabetes.

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