In conclusion, our study demonstrates that decreased endogenous H2S may be involved in the onset of insulin resistance induced by PA, However, exogenous NaHS attenuates PA-induced insulin resistance in C2C12 cells through the phosphorylation and activation of the insulin signalling pathway as well as the protection of mitochondrial function, which was at least partially mediated by the Ca2+-CaMKKβ-AMPK pathway and the PI3K/AKT pathway. Here, INS is linked to Insulin resistance.