title: Ginsenoside Re reduces insulin resistance through inhibition of c-Jun NH2-terminal kinase and nuclear factor-kappaB.
abstract: Ginsenoside Re (Re), a compound derived from Panax ginseng, shows an antidiabetic effect. However, the molecular basis of its action remains unknown. We investigated insulin signaling and the antiinflammatory effect by Re in 3T3-L1 adipocytes and in high-fat diet (HFD) rats to dissect its anti-hyperglycemic mechanism. Glucose uptake was measured in 3T3-L1 cells and glucose infusion rate determined by clamp in HFD rats. The insulin signaling cascade, including insulin receptor (IR) beta-subunit, IR substrate-1, phosphatidylinositol 3-kinase, Akt and Akt substrate of 160 kDa, and glucose transporter-4 translocation are examined. Furthermore, c-Jun NH(2)-terminal kinase (JNK), MAPK, and nuclear factor (NF)-kappaB signaling cascades were also assessed. The results show Re increases glucose uptake in 3T3-L1 cells and glucose infusion rate in HFD rats. The activation of insulin signaling by Re is initiated at IR substrate-1 and further passes on through phosphatidylinositol 3-kinase and downstream signaling cascades. Moreover, Re demonstrates an impressive suppression of JNK and NF-kappaB activation and inhibitor of NF-kappaBalpha degradation. In conclusion, Re reduces insulin resistance in 3T3-L1 adipocytes and HFD rats through inhibition of JNK and NF-kappaB activation.
authors: Laboratory of Endocrinology and Metabolism, Institute of Health Sciences, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai 200025, China.
authors: Zhiguo
authors: Z
authors: Zhang
authors: Xiaoying
authors: X
authors: Li
authors: Wenshan
authors: W
authors: Lv
authors: Yisheng
authors: Y
authors: Yang
authors: Hong
authors: H
authors: Gao
authors: Jun
authors: J
authors: Yang
authors: Yun
authors: Y
authors: Shen
authors: Guang
authors: G
authors: Ning
mesh_terms: D041721:3T3-L1 Cells; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D015153:Blotting, Western; D004041:Dietary Fats / Q000008:administration & dosage; D036145:Ginsenosides / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006943:Hyperglycemia / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control; D047468:Immunoprecipitation; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014443:Tyrosine / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004041:Dietary Fats; D036145:Ginsenosides; D051275:Glucose Transporter Type 4; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; C526296:Irs1 protein, rat; D016328:NF-kappa B; C495693:Slc2a4 protein, mouse; D014443:Tyrosine; C049864:ginsenoside Re; D019869:Phosphatidylinositol 3-Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D005947:Glucose