title: 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.affiliation: Department of Endocrinology, Provincial Hospital Affiliated to Shandong University, Jinan 250021, China ; Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Biochemistry and Molecular Biology, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Wang
authors.identifier: 0000-0002-2171-2205
authors.initials: W
authors.lastname: Li
authors.affiliation: Biochemistry and Molecular Biology, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Biochemistry and Molecular Biology, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Central Laboratory, Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Endocrinology, Provincial Hospital Affiliated to Shandong University, Jinan 250021, China ; Institute of Endocrinology, Shandong Academy of Clinical Medicine, Jinan 250021, China.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000818:Animals; D061745:Antioxidant Response Elements / Q000235:genetics*; D004032:Diet; D059305:Diet, High-Fat; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005943:Gluconeogenesis / Q000187:drug effects / Q000235:genetics; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006019:Glycolysis / Q000187:drug effects / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D007333:Insulin Resistance; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004365:Drugs, Chinese Herbal; D051267:NF-E2-Related Factor 2; C500223:lycium barbarum polysaccharide; D019869:Phosphatidylinositol 3-Kinases; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D038362:Glycogen Synthase Kinase 3