title: Metabolomics reveals the protective of Dihydromyricetin on glucose homeostasis by enhancing insulin sensitivity.
abstract: Dihydromyricetin (DMY), an important flavanone found in Ampelopsis grossedentata, possesses antioxidative properties that ameliorate skeletal muscle insulin sensitivity and exert a hepatoprotective effect. However, little is known about the effects of DMY in the context of high-fat diet (HFD)-induced hepatic insulin resistance. Male Sprague-Dawley(SD) rats were fed a HFD(60% fat) supplemented with DMY for 8 weeks. The administration of DMY to the rats with HFD-induced insulin resistance reduces hyperglycemia, plasma levels of insulin, and steatosis in the liver. Furthermore, DMY treatment modulated 24 metabolic pathways, including glucose metabolism, the TCA cycle. DMY significantly enhanced glucose uptake and improved the translocation of glucose transporter 1. The specificity of DMY promoted the phosphorylation of AMP-activated protein kinase (AMPK). In addition, the exposure of HepG2 cells to high glucose concentrations impaired the insulin-stimulated phosphorylation of Akt2 Ser474 and insulin receptor substrate-1 (IRS-1) Ser612, increased GSK-3β phosphorylation, and upregulated G6Pase and PEPCK expression. Collectively, DMY improved glucose-related metabolism while reducing lipid levels in the HFD-fed rats. These data suggest that DMY might be a useful drug for use in type 2 diabetes insulin resistance therapy and for the treatment of hepatic steatosis.
authors: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, No. 151 Malianwa North Road, Haidian District, Beijing 100193, P. R. China.|Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, P. R. China.
authors: Liang
authors: L
authors: Le
authors: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, No. 151 Malianwa North Road, Haidian District, Beijing 100193, P. R. China.|State Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, No. 151 Malianwa North Road, Haidian District, Beijing 100193, P. R. China.
authors: Baoping
authors: B
authors: Jiang
authors: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, No. 151 Malianwa North Road, Haidian District, Beijing 100193, P. R. China.|State Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, No. 151 Malianwa North Road, Haidian District, Beijing 100193, P. R. China.
authors: Wenting
authors: W
authors: Wan
authors: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, No. 151 Malianwa North Road, Haidian District, Beijing 100193, P. R. China.
authors: Wei
authors: W
authors: Zhai
authors: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, No. 151 Malianwa North Road, Haidian District, Beijing 100193, P. R. China.|State Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, No. 151 Malianwa North Road, Haidian District, Beijing 100193, P. R. China.
authors: Lijia
authors: L
authors: Xu
authors: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, No. 151 Malianwa North Road, Haidian District, Beijing 100193, P. R. China.
authors: Keping
authors: K
authors: Hu
authors: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, No. 151 Malianwa North Road, Haidian District, Beijing 100193, P. R. China.|State Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, No. 151 Malianwa North Road, Haidian District, Beijing 100193, P. R. China.
authors: Peigen
authors: P
authors: Xiao
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D002952:Citric Acid Cycle / Q000187:drug effects; D059305:Diet, High-Fat; D044948:Flavonols / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D007328:Insulin / Q000097:blood; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D044948:Flavonols; C526292:IRS1 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D020011:Protective Agents; D000071679:Glycogen Synthase Kinase 3 beta; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose; C472036:dihydromyricetin