title: Kazinol B from Broussonetia kazinoki improves insulin sensitivity via Akt and AMPK activation in 3T3-L1 adipocytes.
abstract: In this study, we evaluated the insulin-sensitizing effect of flavans purified from Broussonetia kazinoki Siebold (BK) on 3T3-L1 adipocytes. Among the tested compounds, kazinol B enhanced intracellular lipid accumulation, gene expression of proliferator-activated receptorγ (PPARγ) and CCAAT/enhancer binding protein-alpha (C/EBPα), and consistently induced PPARγ transcriptional activation. To further investigate the insulin-sensitizing effect of kazinol B, we measured glucose analogue uptake by fully differentiated adipocytes and myotubes. Kazinol B increased 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose (2-NBDG) uptake by cells by upregulating the gene expression and translocation of glucose transporter 4 (GLUT-4) into the plasma membrane in adipocytes. Kazinol B stimulated the gene expression and secretion of adiponectin, which is associated with a low risk of types 1 and 2 diabetes mellitus. We also suggested the mechanism of the antidiabetic effect of kazinol B by assaying Akt and AMP-activated protein kinase (AMPK) phosphorylation. In conclusion, kazinol B isolated from BK improved insulin sensitivity by enhancing glucose uptake via the insulin-Akt signaling pathway and AMPK activation. These results suggest that kazinol B might be a therapeutic candidate for diabetes mellitus.
authors.affiliation: College of Pharmacy and Research Center for Cell Fate Control, Sookmyung Women's University, 52 Hyochangwon-Gil, Yongsan-Gu, Seoul 140-742, Republic of Korea.
authors.forename: Hyejin
authors.initials: H
authors.lastname: Lee
authors.affiliation: College of Pharmacy and Research Center for Cell Fate Control, Sookmyung Women's University, 52 Hyochangwon-Gil, Yongsan-Gu, Seoul 140-742, Republic of Korea.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: College of Pharmacy and Research Center for Cell Fate Control, Sookmyung Women's University, 52 Hyochangwon-Gil, Yongsan-Gu, Seoul 140-742, Republic of Korea.
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Natural Products Research Institute, College of Pharmacy, Seoul National University, 1 Gwanak-Ro, Gwanak-Gu, Seoul 151-742, Republic of Korea.
authors.forename: Minsoo
authors.initials: M
authors.lastname: Noh
authors.affiliation: College of Pharmacy and Research Center for Cell Fate Control, Sookmyung Women's University, 52 Hyochangwon-Gil, Yongsan-Gu, Seoul 140-742, Republic of Korea. Electronic address: ryuha@sookmyung.ac.kr.
authors.forename: Jae-Ha
authors.initials: JH
authors.lastname: Ryu
mesh_terms: D041721:3T3-L1 Cells; D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives / Q000378:metabolism; D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D017667:Adipocytes / Q000187:drug effects; D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D031623:Broussonetia / Q000737:chemistry*; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007333:Insulin Resistance; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D052242:Adiponectin; D005419:Flavonoids; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D047495:PPAR gamma; C117415:kazinol B; D003847:Deoxyglucose; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases; D009327:4-Chloro-7-nitrobenzofurazan; D005947:Glucose; C098340:2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose
keywords: 3T3-L1; AMPK; Broussonetia kazinoki; Diabetes mellitus; Glucose uptake; Kazinol B (PubChem CID: 480869); Rosiglitazone (PubChem CID: 77999)