Stimulation of Glucose Uptake and Improvement of Insulin Resistance by Aromadendrin

Abstract

Agents that stimulate glucose uptake and improve insulin resistance may be useful in the management of type 2 diabetes mellitus (DM). Thus, the aims of this study were to assess the effects of aromadendrin, a flavonoid from Gleditsia sinensis Lam., on stimulation of glucose uptake and improvement of insulin resistance and to characterize the molecular mechanisms underlying these activities. Insulin-stimulated glucose uptake was measured in HepG2 cells and in differentiated 3T3-L1 adipocytes using 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose (2-NBDG), a fluorescent D-glucose analog. Expression of the peroxisome proliferator-activated receptor-γ2 (PPARγ2) and adipocyte-specific fatty acid binding protein (aP2) mRNAs and the PPARγ2 protein was analyzed in adipocytes using RT-PCR and immunoblotting, respectively. Insulin-stimulated protein kinase B (Akt/PKB) phosphorylation was measured in high glucose-induced, insulin-resistant HepG2 cells. Similar to 30 µmol/l rosiglitazone, treatment with 30 µmol/l aromadendrin significantly stimulated insulin-sensitive glucose uptake in both HepG2 cells and 3T3-L1 adipocytes. Aromadendrin treatment also enhanced adipogenesis and caused increases in the expression of PPARγ2 and aP2 mRNAs and the PPARγ2 protein in differentiated 3T3-L1 adipocytes. In high glucose-induced, insulin-resistant HepG2 cells, aromadendrin reversed the inhibition of Akt/PKB phosphorylation in response to insulin, which could be abrogated by pretreatment with LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor. Aromadendrin treatment induced adipogenesis by increases in PPARγ2 expression, resulting in stimulation of glucose uptake and ameliorated insulin resistance. These findings suggest that aromadendrin may represent a potential therapeutic candidate for the management of type 2 DM.

Ethanol extract of Gleditsia sinensis thorn suppresses angiogenesis in vitro and in vivo

“…The single compounds from the fruits or anomalous fruits of Gleditsia sinensis have been isolated as triterpene (echinocystic acid), flavonoid (aromadendrin), polyphenol (ellagic acid glycosides), and triterpenoid saponins (gleditsioside A-K, N-Q, and Z) [31-40]. Their identified pharmacological activities were antagonistic against dopamine D1 receptor (gleditsioside F) [33], protective against acute myocardial ischemia (echinocystic acid) [32] or type 2 diabetes mellitus (aromadendrin) [35], antiallergic in mast cells (saponins) [41], and cytotoxic to leukemic cells (gleditsioside E) [38]. The single compounds from the Gleditsia sinensis thorns were isolated as a lupane acid with anti-HIV activity [42], and triterpenoid (D:C-friedous-7-en-3-one) and sterols with antimutagenic activity [43].…”

Visualizing Sweetness: Increasingly Diverse Applications for Fluorescent-Tagged Glucose Bioprobes and Their Recent Structural Modifications

“…, the promotion of glucose uptake in insulin-sensitive cells, such as adipocytes and skeletal muscle cells ( i.e. , see [50–54]). Secondly, in cancer research, there has been increasing focus on targeting tumor cell metabolism to develop cancer drugs (reviewed in references [55–57]).…”

Quercetin-3-O-β-D-Glucuronide Suppresses Lipopolysaccharide-Induced JNK and ERK Phosphorylation in LPS-Challenged RAW264.7 Cells

“…It has been extensively reported that LPS activates all three MAP kinases such as ERK, JNK, and p38 in macrophages (Sweet and Hume, 1996) and that many of the downstream targets of MAPK pathways are transcription factors, which regulate various genes encoding inflammatory mediators (Zhang et al ., 2006; Lee et al ., 2009; Zhang et al ., 2011). In the present study, LPS treatment exhibited increased phosphorylation of all three MAPKs in RAW264.7 cells.…”