Two triterpeniods from Cyclocarya paliurus (Batal) Iljinsk (Juglandaceae) promote glucose uptake in 3T3-L1 adipocytes: The relationship to AMPK activation

Purpose: The current study investigated the efficacy of Cyclocarya poliurus 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-Li 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-kappa B kinase beta(IKK beta) 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 IKK beta, 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 IKK beta 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-PI3K/Akt pathway by inhibiting inflammation. These effects were related to the regulation of AMPK activity. (C) 2015 Published by Elsevier GmbH. All rights reserved.