Department of Pharmacology, Chungnam National University College of Pharmacy, Daejeon, Republic of Korea.
Pharmacology. 2011;88(5-6):266-74. doi: 10.1159/000331862. Epub 2011 Nov 1.
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.
刺激葡萄糖摄取并改善胰岛素抵抗的药物可能对 2 型糖尿病（DM）的治疗有用。因此，本研究的目的是评估从皂荚中提取的橙皮素对刺激葡萄糖摄取和改善胰岛素抵抗的作用，并阐明其作用机制。使用 2-[N-(7-硝基苯并-2-氧代-1,3-二唑-4-基)氨基]-2-脱氧-D-葡萄糖（2-NBDG），一种荧光 D-葡萄糖类似物，在 HepG2 细胞和分化的 3T3-L1 脂肪细胞中测量胰岛素刺激的葡萄糖摄取。使用 RT-PCR 和免疫印迹法分别分析脂肪细胞中过氧化物酶体增殖物激活受体-γ2（PPARγ2）和脂肪细胞特异性脂肪酸结合蛋白（aP2）mRNA 的表达和 PPARγ2 蛋白。使用高葡萄糖诱导的胰岛素抵抗 HepG2 细胞测量胰岛素刺激的蛋白激酶 B（Akt/PKB）磷酸化。与 30 μmol/l 罗格列酮相似，30 μmol/l 橙皮素处理可显著刺激 HepG2 细胞和 3T3-L1 脂肪细胞中胰岛素敏感的葡萄糖摄取。橙皮素处理还增强了脂肪生成，并导致分化的 3T3-L1 脂肪细胞中 PPARγ2 和 aP2 mRNA 和 PPARγ2 蛋白的表达增加。在高葡萄糖诱导的胰岛素抵抗 HepG2 细胞中，橙皮素逆转了胰岛素对 Akt/PKB 磷酸化的抑制作用，而用磷脂酰肌醇 3-激酶（PI3K）抑制剂 LY294002 预处理则可消除这种作用。橙皮素处理通过增加 PPARγ2 表达诱导脂肪生成，从而刺激葡萄糖摄取并改善胰岛素抵抗。这些发现表明，橙皮素可能成为 2 型糖尿病治疗的潜在候选药物。
