Nobiletin activated mitogen-activated protein kinase-extracellular signal-related kinase (MAPK/ERK), resulting in the marked inhibition of apolipoprotein B100 secretion. It neither induced the phosphorylation of the insulin receptor (IR) or insulin receptor substrate-1(IRS-1) tyrosine nor triggered lipogenesis associated with insulin resistance. This evidence concerns the gene IRS1 and Insulin resistance.