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Lycium barbarum  polysaccharide (LBP), an antioxidant from  wolfberry , displays the antioxidative and anti-inflammatory effects on experimental models of insulin resistance  in vivo . However, the effective mechanism of LBP on high-fat diet-induced insulin resistance is still unknown. The objective of the study was to investigate the mechanism involved in LBP-mediated phosphatidylinositol 3-kinase (PI3K)/AKT/Nrf2 axis against high-fat-induced insulin resistance. HepG2 cells were incubated with LBP for 12 hrs in the presence of palmitate. C57BL/6J mice were fed a high-fat diet supplemented with LBP for 24 weeks. We analyzed the expression of nuclear factor-E2-related factor 2 (Nrf2), Jun N-terminal kinases (JNK), and glycogen synthase kinase 3 β  (GSK3 β ) involved in insulin signaling pathway  in vivo  and  in vitro .  First , LBP significantly induced phosphorylation of Nrf2 through PI3K/AKT signaling.  Second , LBP obviously increased detoxification and antioxidant enzymes expression and reduced reactive oxygen species (ROS) levels via PI3K/AKT/Nrf2 axis.  Third , LBP also regulated phosphorylation levels of GSK3 β  and JNK through PI3K/AKT signaling.  Finally , LBP significantly reversed glycolytic and gluconeogenic genes expression via the activation of Nrf2-mediated cytoprotective effects. In summary, LBP is novel antioxidant against insulin resistance induced by high-fat diet via activation of PI3K/AKT/Nrf2 pathway.

oxidative medicine and cellular longevity

Dietary <i>Lycium barbarum</i> Polysaccharide Induces Nrf2/ARE Pathway and Ameliorates Insulin Resistance Induced by High-Fat via Activation of PI3K/AKT Signaling

Dietary Lycium barbarum Polysaccharide Induces Nrf2/ARE Pathway and Ameliorates Insulin Resistance Induced by High-Fat via Activation of PI3K/AKT Signaling