NOS3 and Insulin resistance: This improvement in insulin resistance was associated with the activation of insulin receptor signaling and adiponectin-mediated AMPK signaling pathways.442,446 CYP2J3 gene delivery markedly reversed insulin resistance via upregulated AMPK signaling, which was associated with decreased ER stress response in adipose tissue.442 CYP2J3-derived EETs alleviate insulin resistance, at least in part through upregulated endothelial nitric oxide synthase expression in rats treated with fructose, which was associated with activation of MAPK and protein kinase C signaling pathways.