Dietary Lycium barbarum polysaccharide induces Nrf2/ARE pathway and ameliorates insulin resistance induced by high-fat via activation of PI3K/AKT signaling.

Abstract

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 3β (GSK3β) 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 GSK3β 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.

• Authors: Yi Yang, Wang Li, Yan Li, Qing Wang, Ling Gao, Jiajun Zhao
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2014 Pg. 145641 ( 2014) ISSN: 1942-0994 [Electronic] United States
• PMID: 25045414 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Drugs, Chinese Herbal
• NF-E2-Related Factor 2
• lycium barbarum polysaccharide
• Phosphatidylinositol 3-Kinases
• GSK3B protein, human
• Glycogen Synthase Kinase 3 beta
• Gsk3b protein, mouse
• Proto-Oncogene Proteins c-akt
• JNK Mitogen-Activated Protein Kinases
• Glycogen Synthase Kinase 3

Topics

• Animals
• Antioxidant Response Elements (genetics)
• Diet
• Diet, High-Fat
• Drugs, Chinese Herbal (pharmacology)
• Enzyme Activation (drug effects)
• Gene Expression Regulation (drug effects)
• Gluconeogenesis (drug effects, genetics)
• Glycogen Synthase Kinase 3 (metabolism)
• Glycogen Synthase Kinase 3 beta
• Glycolysis (drug effects, genetics)
• Hep G2 Cells
• Humans
• Insulin Resistance
• JNK Mitogen-Activated Protein Kinases (metabolism)
• Liver (drug effects, metabolism)
• Male
• Mice, Inbred C57BL
• NF-E2-Related Factor 2 (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphorylation (drug effects)
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction (drug effects)