title: Two triterpeniods from Cyclocarya paliurus (Batal) Iljinsk (Juglandaceae) promote glucose uptake in 3T3-L1 adipocytes: The relationship to AMPK activation.
abstract: OBJECTIVE
  The current study investigated the efficacy of Cyclocarya paliurus chloroform extract (CPEC) and its two specific triterpenoids (cyclocaric acid B and cyclocarioside H) on the regulation of glucose disposal and the underlying mechanisms in 3T3-L1 adipocytes.
  
  
  METHODS
  Mice and adipocytes were stimulated by macrophages-derived conditioned medium (Mac-CM) to induce insulin resistance. CPEC was evaluated in mice for its ability by oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). To investigate the hypoglycemic mechanisms of CPEC and its two triterpenoids, glucose uptake, AMP-activated protein kinase (AMPK) activation, inhibitor of NF-κB kinase β (IKKβ) phosphorylation and insulin signaling transduction were detected in 3T3-L1 adipocytes using 2-NBDG uptake assay and Western blot analysis.
  
  
  RESULTS
  Mac-CM, an inflammatory stimulus which induced the glucose and insulin intolerance, increased phosphorylation of IKKβ, reduced glucose uptake and impaired insulin sensitivity. CPEC and two triterpenoids improved glucose consumption and increased AMPK phosphorylation under basal and inflammatory conditions. Moreover, CPEC and its two triterpenoids not only enhanced glucose uptake in an insulin-independent manner, but also restored insulin-mediated protein kinase B (Akt) phosphorylation by reducing the activation of IKKβ and regulating insulin receptor substrate-1 (IRS-1) serine/tyrosine phosphorylation. These beneficial effects were attenuated by AMPK inhibitor compound C, implying that the effects may be associated with AMPK activation.
  
  
  CONCLUSIONS
  CPEC and its two triterpenoids promoted glucose uptake in the absence of insulin, as well as ameliorated IRS-1/PI3K/Akt pathway by inhibiting inflammation. These effects were related to the regulation of AMPK activity.
authors.affiliation: Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, PR China; Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, PR China.
authors.forename: K N
authors.initials: KN
authors.lastname: Zhu
authors.affiliation: Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China.
authors.forename: C H
authors.initials: CH
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, PR China.
authors.forename: Y S
authors.initials: YS
authors.lastname: Tian
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, PR China.
authors.forename: N
authors.initials: N
authors.lastname: Xiao
authors.affiliation: Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, PR China; Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China.
authors.forename: Z F
authors.initials: ZF
authors.lastname: Wu
authors.affiliation: Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, PR China; Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China.
authors.forename: Y L
authors.initials: YL
authors.lastname: Ma
authors.affiliation: Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, PR China; Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China.
authors.forename: Z
authors.initials: Z
authors.lastname: Lin
authors.affiliation: College of Forest Resources and Environment, Nanjing Forestry University, Nanjing 210042, Jiangsu Province, PR China.
authors.forename: S Z
authors.initials: SZ
authors.lastname: Fang
authors.affiliation: College of Forest Resources and Environment, Nanjing Forestry University, Nanjing 210042, Jiangsu Province, PR China.
authors.forename: X L
authors.initials: XL
authors.lastname: Shang
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, PR China.
authors.forename: K
authors.initials: K
authors.lastname: Liu
authors.affiliation: Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, PR China. Electronic address: njlbl55@sohu.com.
authors.forename: B L
authors.initials: BL
authors.lastname: Liu
authors.affiliation: Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, PR China. Electronic address: chyzq2005@126.com.
authors.forename: Z Q
authors.initials: ZQ
authors.lastname: Yin
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005947:Glucose / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000737:chemistry; D051550:I-kappa B Kinase / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D029525:Juglandaceae / Q000737:chemistry*; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010766:Phosphorylation; D010936:Plant Extracts / Q000737:chemistry*; D018515:Plant Leaves / Q000737:chemistry; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D014315:Triterpenes / Q000737:chemistry*
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D010936:Plant Extracts; D014315:Triterpenes; D051057:Proto-Oncogene Proteins c-akt; D051550:I-kappa B Kinase; D055372:AMP-Activated Protein Kinases; D005947:Glucose
keywords: AMPK; Cyclocaric acid B (CAS No. 182315-46-4); Cyclocarioside H (CAS No. 1403937-87-0); Cyclocarya paliurus; Glucose uptake; Inflammation; Insulin resistance; Triterpenoids