Effect of young apple (Malus domestica Borkh. cv. Red Fuji) polyphenols on alleviating insulin resistance

Abstract Insulin resistance (IR) has an important role in the development of type 2 diabetes (T2DM). This study aimed to investigate the effect of young apple (Malus domestica Borkh. cv. Red Fuji) polyphenols (YAP) on IR in HepG2 cells. It was found that YAP and its two main components, phlorizin and chlorogenic acid, could increase glucose uptake, glucose consumption and glycogen content. YAP and phlorizin activated the insulin receptor substrate 2/phosphatidylinositol 3-kinase/phosphorylation of the protein kinase B (IRS2/PI3K/AKT) signal pathway, as well as its downstream proteins glycogen synthase kinase-3β (GSK3β) and forkhead box protein O1 (FOXO1), which were further confirmed by application of the PI3K inhibitor LY294002. YAP and phlorizin also improved mitochondrial dysfunction by reducing mitochondrial reactive oxygen species (ROS) accumulation, restoring ATP production and the mitochondrial membrane potential (MMP). This study suggested that YAP has the potential to alleviate T2DM symptoms.