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Aims: <b>Nelumbo nucifera</b> (Gaertn.) leaves are used widely in modulating obesity in traditional Chinese medicine. Our previous work demonstrated that aporphine alkaloids from it increased the glucose consumption in mature 3T3-L1 adipocytes. However, the underlying mechanisms of this increase remain unclear. Here we investigated the modulating effects of pronuciferine and nuciferine on lipogenesis and glucose uptake in insulin resistant 3T3-L1 adipocytes <b>in vitro</b>.<br>Main methods: Insulin resistant 3T3-L1 mature adipocytes were induced with dexamethasone, 3-isobutyl-methylxanthine and insulin. The lipid droplets and the intracellular triglyceride contents in mature adipocytes were detected by Oil red O staining and colorimetry respectively. The glucose uptake was measured with a fluorescent deoxyglucose analog (2-NBDG). The glucose transporter type 4 (GLUT-4) expression was measured by fluorescent-immunohistochemistry and the activation of 5′-AMP-activated protein kinase (AMPK) was detected by its alpha subunit phosphorylation.<br>Key findings: Both nuciferine and pronuciferine treatments significantly decreased the lipid droplets and the intracellular triglyceride contents but increased the glucose uptake in the insulin resistant 3T3-L1 adipocytes. Furthermore, both pronuciferine and nuciferine showed the ability to up-regulate the expression of GLUT4, triggering the phosphorylation of AMPK in mature 3T3-L1 adipocytes, although pronuciferine exhibited a more powerful effect compared to nuciferine.<br>Significance: In summary, all the results demonstrate that pronuciferine and nuciferine ameliorate the glucose and lipid metabolism in insulin-resistant 3T3-L1 adipocytes, which might be due to the activation of the AMPK signaling pathway.