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Objective: Insulin resistance is a hallmark of type 2 diabetes mellitus (T2DM).In this study, the effects of genipin, which is the extract of Gardenia jasminoides Ellis fruits, on insulin resistance and the relevant mechanisms were explored in palmitate-treated L02 hepatocytes.Methods: L02 cells were cultivated in 0.15mM sodium palmitate with or without genipin for 24 h.The glucose consumption and the glycogen synthesis were evaluated in basal and insulin-stimulated status by commercial kits.The mitochondrial membrane potential (MMP) and intracellular reactive oxygen species (ROS) were detected by fluorescence spectrophotometry.An bioluminescence assay kit was used to determine the intracellular ATP level.Results: Genipin promoted insulinstimulated glucose consumption and glycogen synthesis impaired by palmitate.In addition, genipin alleviated palmitate-induced mitochondrial dysfunction through elevation of MMP and ATP levels, and reduction of ROS content.Conclusion: Genipin increased insulin sensitivity in palmitate-treated L02 hepatocytes, in which the improvement of mitochondial functions was involved.