Effect of ginsenosides Rg3 and Re on glucose transport in mature 3T3-L1 adipocytes

Ginsenosides, the active component of Panax ginseng, have been shown to evidence a variety of biological activities associated with hyperglycemia, obesity and type 2 diabetes mellitus. This study evaluated the effects of the ginsenosides, Rg3 and Re, on glucose uptake and the glucose transport system in mature 3T3‐L1 cells. The results demonstrated that the glucose uptake of ginsenosides Rg3 and Re at concentrations of 1–10 µM significantly increased by approximately ～10% and ～12%, respectively. Furthermore, the glucose transporter 4 (GLUT4) mRNA expression of ginsenosides Rg3 and Re at 10 µM was increased by approximately ～1.73 and 1.43 fold, respectively. It was further confirmed in a series of experiments that ginsenosides Rg3 and Re stimulated the mRNA expression of insulin receptor substrate (IRS‐1) and the expression of phosphatidylinositol 3‐kinase (PI3K)‐110α protein, which is involved in downstream events in the insulin signaling pathway. These findings demonstrate that ginsenosides Rg3 and Re may stimulate glucose uptake via the PI3K pathways involving IRS‐1. Further, our results suggest that both of these ginsenosides might prove useful as effective antidiabetic and antihyperglycemic agents. Copyright © 2010 John Wiley & Sons, Ltd.     

当药黄素治疗2型糖尿病的作用机制及研究进展

2型糖尿病（type 2 diabetes mellitus,T2DM）是一种由多因素导致的系统代谢紊乱疾病,可能由胰岛β细胞的胰岛素分泌缺陷、肌肉组织对葡萄糖的摄取减少、肝糖原输出量增加、脂代谢紊乱、肠促胰岛素效应减弱、肾脏对葡萄糖的处理失调和神经递质紊乱等造成。目前,T2DM的治疗机制主要是通过增加胰岛素的分泌,减少肝糖原的输出,抑制肠道葡萄糖的摄取和吸收,改善C肽的分泌来实现。当药黄素是酸枣仁、菥蓂和淡竹叶等的主要活性成分之一,可诱导干细胞分化成胰岛素产生细胞,调节胰岛素分泌、干预肌肉组织和肝糖原的代谢过程,抑制糖脂和神经递质代谢紊乱,抑制炎症和氧化应激反应的发生,此外还有抗炎、抗氧化、增强记忆力等作用。通过查阅近年来国内外当药黄素治疗T2DM的作用机制,对其分析归纳整理,为T2DM的治疗和研究提供科学的理论依据。     

Antiobesity effect of ginsenoside Rg3 involves the AMPK and PPAR-gamma signal pathways

Ginsenosides, the active component of ginseng, exerts antidiabetic and anticancer effects. This study investigated the molecular basis of ginsenoside Rg3, a red ginseng rich constituent, focusing on its ability to inhibit adipocyte differentiation in 3T3-L1 cells. The data show that ginsenoside Rg3 was effective in the inhibition of adipocyte differentiation. This inhibitory effect of ginsenoside Rg3 on adipocyte differentiation was accompanied by PPAR-gamma inhibition in rosiglitazone-treated cells. The study also tested whether AMP-activated protein kinase (AMPK) activation was involved in the inhibitory effects of ginsenoside Rg3. AMPK plays a role in maintaining health in the context of diseases such as type 2 diabetes, obesity and cancer. AMPK was reported to control nutritional and hormonal signal modulating. Rg3 significantly and time-dependently activated AMPK. Taken together, these results suggest that the antiobesity effect of red ginseng rich constituent, ginsenoside Rg3, involves the AMPK signaling pathway and PPAR-gamma inhibition.     

Coriolus versicolor aqueous extract ameliorates insulin resistance with PI3K/Akt and p38 MAPK signaling pathways involved in diabetic skeletal muscle

Patients with type 2 diabetes mellitus (T2DM) are usually with poor immunity and easier to suffer from cancer and microbial infections. Herein, we report an efficient anti‐diabetic medicinal mushroom, Coriolus versicolor (CV). This study aimed to investigate the anti‐diabetic and anti‐insulin‐resistance effects of CV aqueous extract in myoblasts (L6 cells) and skeletal muscle of T2DM rat. Our results showed that CV extract treatment significantly reduced blood glucose levels of T2DM rats, whereas CV extract increased glucose consumption in insulin resistant L6 cells. Besides, the translocation and expression of glucose transporter 4 were enhanced by CV extract, which indicated that CV extract was effective in diabetic skeletal muscle. Moreover, CV extract treatments resulted in remarkable anti‐insulin‐resistance effects, which was reflected by the change of gene and protein expression levels in PI3K/Akt and p38 MAPK pathways. PI3K inhibitor, LY29004, and p38 MAPK inhibitor, SB203580 confirmed it further. In conclusion, our results demonstrated that the CV extract exhibited anti‐diabetic and anti‐insulin‐resistance effects in diabetic skeletal muscle, and the effects were mediated by PI3K/Akt and p38 MAPK pathways. These findings are remarkable when considering the use of commercially available CV by diabetic patients who also suffer from cancer or microbial infections.     

2型糖尿病眼肌麻痹患者胰岛素抵抗、脂代谢紊乱与神经病变的关系

目的探讨2型糖尿病眼肌麻痹患者胰岛素抵抗、脂代谢紊乱与神经病变的关系。方法对56例2型糖尿病眼肌麻痹患者(T2DM+OMP)、56例2型单纯糖尿病患者(T2DM)及56例健康对照者(HC)进行隔夜空腹12 h血糖(FBG)、胰岛素(FINS)、糖化血红蛋白(HbA1c)、血清总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)检测并进行分析,用稳态模型方法评估各组人群空腹胰岛素抵抗指数(HOMA-IR)、胰岛素敏感指数(ISI)及胰岛β细胞功能(HOMA-β)。结果 T2DM+OMP组FBG、FINS、HOMA-IR、HbA1c、TC、TG、LDL-C浓度均显著高于T2DM组及HC组(P均<0.01),ISI、HOMA-β、HDL-C血清浓度显著低于T2DM组及HC组(P均<0.01)。T2DM组FBG、FINS、HOMA-IR、HbA1c、TC、TG浓度高于HC组(P均<0.05),T2DM组ISI、HOMA-β、HDL-C浓度低于HC组(P均<0.01)。结论胰岛素抵抗、脂代谢紊乱极大地促进了糖尿病微血管及神经病变的发生和发展,控制血糖、改善脂代谢异常、减少胰岛素抵抗、保护胰岛β细胞功能对预防和治疗2型糖尿病神经病变有指导意义。     

西洋参活性成分对胰岛素抵抗脂肪细胞模型脂肪细胞因子分泌的影响

目的:通过测定游离脂肪酸(FFA)、白介素-6(IL-6)、干扰素(INF)等脂肪细胞因子的浓度,从而探讨西洋参活性成分对胰岛素抵抗脂肪细胞模型脂肪细胞因子分泌的影响。方法:通过高糖高胰岛素刺激,建立胰岛素抵抗脂肪细胞模型,随机分为空白组、模型组、罗格列酮组、20(R)人参皂苷Rb1组、20(R)人参皂苷Rb2组、人参皂苷R3组、拟人参皂苷F11组、西洋参复合成分组。药物干预培养24h后,检测各组脂肪细胞因子的浓度。结果:与模型组细胞FFA分泌量比较,20(R)人参皂苷Rb1组、20(R)人参皂苷Rb2组、西洋参复合成分组、罗格列酮组FFA分泌量明显降低,差异极显著(P<0.01),拟人参皂苷F11组也有显著差异(P<0.05),其余无统计学差异;与模型组细胞IL-6分泌量比较,罗格列酮组、拟人参皂苷F11组、西洋参复合成分组、20(R)人参皂苷Rb1组细胞IL-6分泌量均降低,差异极显著(P<0.01),其余无统计学差异;与模型组细胞INF分泌量比较,人参皂苷R3组、西洋参复合成分组、20(R)人参皂苷Rb1组INF分泌量明显降低,差异极显著(P<0.01),拟人参皂苷F11组、罗格列酮组也有显著差异(P<...     

Amelioration of insulin resistance using the additive effect of ferulic acid and resveratrol on vesicle trafficking for skeletal muscle glucose metabolism

Dysregulation of vesicle trafficking in muscle is one of the factors responsible for the pathogenesis of insulin resistance (IR). Ferulic acid (FER) and resveratrol (RSV) are known to have hypoglycemic property. In this study, differentiated L6 myotubes were induced with palmitate as a model of IR. Chemical ablation of muscle vesicles was used to investigate how FER and RSV influence glucose utilization. Results showed that both FER and RSV elicit glucose uptake and promote glycogen synthesis in insulin‐resistant muscle cells. Mechanistic studies further showed that FER markedly enhances the transferrin receptor‐containing endosomal compartment activities via phosphoinositide 3‐kinase (PI3K)/atypical protein kinase C‐dependent pathway, while RSV facilitates glucose transporter storage vesicles (GSV) trafficking via an exercise‐like effect of conventional protein kinase C/5′‐adenosine monophosphate‐activated protein kinase (AMPK) modulation. Therefore, these two phenolic compounds promoted glucose transport through two separate routes, and they had an additive effect on the increase of glucose uptake in insulin‐resistant muscle cells. These findings provide a basis for the understanding of the antidiabetic potential of RSV and FER combination.     

罗格列酮治疗2型糖尿病疗效观察

目的观察胰岛素增敏剂马来酸罗格列酮(RSG)对2型糖尿病(T2DM)患者血糖、血压、血脂和胰岛素抵抗(IR)的影响,并检测治疗前后血清脂联素水平的变化。方法用计算机随机双盲法比较58例T2DM患者日服RSG 4 mg和安慰剂(1∶1)干预治疗12周后血糖、血脂、血压、IR、血清脂联素水平改变。结果罗格列酮治疗12周后,空腹血糖和餐后2 h(2 hPG)血糖、糖化血红蛋白(HbA1c)、空腹胰岛素(FINS)、HOMA模型IR指数(HOMA-IR)、收缩压(SBP)、舒张压(DBP)、血清总胆固醇(TC)、三酰甘油(TG)均较治疗前降低(P<0.01和0.05);血清脂联素水平显著升高(P<0.01)。上述指标与安慰剂组比较均有显著性差异(P<0.05或0.01)。结论RSG可改善T2DM患者的血糖、血脂代谢,降低IR,降低血压并升高血清脂联素水平,有助于防治T2DM的血管并发症。     

Ginsenoside Rc,an active component of Panax ginseng, stimulates glucose uptake in C2C12 myotubes through an AMPK-dependent mechanism

Ethnopharmacological relevance

Panax ginseng and its major component, ginsenosides, are widely used for the prevention of various disorders in oriental medicine.

Aim of the study

To evaluate the effect of ginsenoside Rc (Rc), one of the active constituents in Panax ginseng, on glucose uptake in C2C12 myotubes.

Results

Treatment of the C2C12 myotubes with Rc significantly increased glucose uptake. To determine the mechanism of Rc-induced glucose uptake, either insulin-dependent signaling or insulin-independent signaling pathway activities were measured using western blot analysis. We showed that Rc significantly activated an insulin-independent AMPK signaling pathway. However, Rc had no effect on the components of the insulin-dependent signaling pathway, such as receptor substrates (IRS)-1 and protein kinase B or Akt (PKB/Akt). Moreover, we found that treatment with an AMPK inhibitor abolished both glucose uptake and p38 MAPK phosphorylation. This result implies that AMPK activity is critical for the Rc-induced glucose uptake and that AMPK is situated upstream of p38 MAPK. In addition, we also showed that the activation of AMPK and p38 induced by ginsenoside Rc is mediated by reactive oxygen species (ROS) production, suggesting that upstream regulators of AMPK- and p38 MAPK-mediated glucose uptake.

Conclusion

Ginsenoside Rc significantly enhances glucose uptake by inducing ROS generation, which leads to AMPK and p38 MAPK activation. Consequently, ginsenoside Rc can be used as a potent natural anti-diabetic agent.     

人参皂甙Rg1对体外微环境诱导人骨髓间充质干细胞成血管内皮样细胞分化的影响

目的 探讨人参皂甙Rg1在体外微环境诱导分化人骨髓间充质干细胞（human mesenchymal stem cells, hMSCs）成血管内皮样细胞的影响。 方法 采用模拟体内微环境的半透膜隔离非接触共培养的方法 体外诱导hMSCs向内皮细胞表型分化, 通过RT-PCR检测内皮细胞标志物血小板内皮黏附分子-1（CD31）、血管性血友病因子（vWF）、血管内皮钙黏蛋白（VE-cadherin）mRNA的表达,免疫荧光染色检测CD31蛋白和血管内皮黏附分子-1（VCAM1）的表达。透射电镜观察诱导后细胞的超微结构鉴定诱导细胞的特征,并通过流式细胞仪检测诱导细胞CD31表达百分比。 结果 与成熟内皮共培养的骨髓基质干细胞具有微环境依赖性向内皮分化的能力。细胞培养第2周,开始出现形态学改变,胞体回缩,呈多角形改变。细胞培养第3周,细胞增殖速度明显加快,形态学上呈卵圆形或“铺路石”样改变;在基因水平上,RT-PCR显示经典内皮细胞标志物CD31、vWF、VE-cadherin mRNA的高表达;在蛋白水平上,免疫荧光染色CD31     

Ginsenoside Rg1 modulation on thrombospondin-1 and vascular endothelial growth factor expression in early renal fibrogenesis in unilateral obstruction

Renal interstitial fibrosis is the major histopathological change seen in a variety of renal disorders and is closely related to renal dysfunction. Progressive interstitial fibrosis accompanied by the loss of renal tubules and interstitial capillaries typifies all progressive renal disease. Thrombospondin-1 (TSP-1) is a major angiogenic inhibitor. It is demonstrated that TSP-1 levels were correlated with the loss of glomerular and peritubular capillaries and TSP-1 could promote renal scarring by effects on the endothelium. It has been reported that ginsenoside Rg1 inhibited renal interstitial fibrosis in rats via suppressing the expression of TSP-1. The present study was designed to examine whether ginsenoside Rg1 could modulate the integrity of the microvasculature and hence affect the progression of renal fibrosis in a rat unilateral ureteral obstruction (UUO) model. In UUO control kidneys, associated with interstitial fibrosis, lower peritubular capillary densities were prominent. These changes were all improved by ginsenoside Rg1 treatment. Interestingly, ginsenoside Rg1 decreased the expression of TSP-1 and enhanced vascular endothelial growth factor (VEGF) expression. The results show for the first time that ginsenoside Rg1 can evidently inhibit renal interstitial fibrosis in rats with UUO. The mechanism might be related to suppression of the expression of TSP-1 and to repair of the peritubular capillary.     

Cardamonin stimulates glucose uptake through translocation of glucose transporter-4 in L6 myotubes

Glucose transporter-4 (GLUT4) is a transmembrane protein that plays a major role in insulin-mediated glucose transport in muscle and adipocytes. For glucose transport to occur, the GLUT4 protein needs to be translocated from the intracellular pool to the plasma membrane, and certain compounds may enhance this process. The present study investigated the promotion of glucose uptake in differentiated L6 myotubes by cardamonin, isolated from Alpinia katsumadai. Cardamonin increased translocation of GLUT4 to the plasma membrane in L6 cells, but did not activate protein kinase C ζ/λ, Akt, or AMP-activated protein-kinase, all of which are known to regulate GLUT4 translocation. The glucose-uptake-promoting activity of cardamonin was not lowered by treatment with a phosphatidylinositol 3'-kinase inhibitor. These results suggest that cardamonin is a promising active compound for maintaining glucose homeostasis, and that it acts via an unknown mechanism that does not involve activation of the downstream insulin signal and AMP-activated protein kinase.     

芪黄胶囊对2型糖尿病患者胰岛素抵抗及TNF-α影响的临床研究

目的研究芪黄胶囊对2型糖尿病患者胰岛素抵抗（IR）及肿瘤坏死因子-α（TNF-α）的影响,观察芪黄胶囊延缓2型糖尿病及其并发症的疗效和机制。方法气阴两虚型2型糖尿病患者80例,随机分为治疗组（芪黄胶囊＋二甲双胍治疗组）和对照组（二甲双胍组）。两组均以2个月为1疗程,治疗前后中医证候疗效判定,观察治疗前后TNF-α、体重指数（BMI）、血脂、糖化血红蛋白（HbA1c）、空腹血糖（FBG）、餐后2h血糖（2hPBG）、空腹胰岛素（FINS）,计算胰岛素敏感指数（IAI）、IR指数（HOMA-IR）。结果芪黄胶囊可显著降低气阴两虚型2型糖尿病患者TNF-α水平,改善患者的中医证候,同时具有良好的降糖、降脂作用,增加胰岛素敏感性,改善IR的作用,与对照组比较有统计学意义。结论芪黄胶囊治疗可明显降低气阴两虚型2型糖尿病患者TNF-α水平,增加胰岛素敏感性,改善IR。     

苦瓜胶囊治疗2型糖尿病胰岛素抵抗的临床观察

目的:观察苦瓜胶囊联合西药治疗2型糖尿病胰岛素抵抗的临床疗效。方法:将2型糖尿病患者86例按随机、单盲原则分为治疗组、对照组各43例;治疗组在西药治疗的同时加服苦瓜胶囊,对照组予单纯西药治疗,疗程为14周。观察2组患者糖化血红蛋白(HbA_(1c))、胰岛素抵抗指数(HOMA-IR)、胰岛素分泌指数(HOMA-β)、糖负荷后30分钟胰岛素净增值/葡萄糖净增值(△I30/△G30)。结果:1)2组患者治疗后HbA_(1c)、血糖较治疗前均明显改善(P0.05),2组治疗后比较差异有统计学意义(P0.05);2)2组患者治疗后空腹胰岛素、C肽及服糖后30分钟胰岛素、C肽较治疗前均明显改善(P0.05),2组治疗后比较差异有统计学意义(P0.05);3)2组患者治疗后HOMA-IR、HOMA-β、糖负荷后30分钟△I30/△G30较治疗前均明显改善(P0.05),2组治疗后比较差异有统计学意义(P0.05);4)2组患者治疗后总胆固醇(TC)、甘油三酯(TG)、脂联素(APN)较治疗前均明显改善,且治疗组在改善TG、APN方面优于对照组(P0.05)。结论:苦瓜胶囊联合西药改善2型糖尿病患者胰岛素抵抗的疗效优于单纯西药。     

Ginsenoside Re reduces insulin resistance through activation of PPAR-γ pathway and inhibition of TNF-α production

Ethnopharmacological relevance

Panax ginseng is a well-known traditional Chinese medicine and has been used for treatment of various diseases for more than four thousand years in Asia. Ginseng saponins or ginsenosides, the active constituents are reported to possess antidiabetic activity, but their antihyperglycemic mechanisms are not fully elucidated. In the present study, the mechanisms of action of ginsenoside Re were investigated in vitro models.

Materials and methods

3T3-L1 cells were chosen as the model to investigate the molecular mechanisms of action of ginsenoside Re. Influence of ginsenoside Re on the adipogenesis was examined by determining TG levels in 3T3-L1 adipocytes by the method of TG oxidation enzyme. Glucose uptake in 3T3-L1 cells stimulated by insulin in the absence or presence of ginsenoside Re were quantified by measuring ³H-2-deoxy-d-glucose levels. Cytokine proteins released into the medium including adiponectin and TNF-α were tested using respective ELISA kits. In addition, real time RT-PCR was conducted to investigate the expression changes of PPAR-γ and its responsive genes, ap2, adiponectin, IRS-1, GLUT4 and TNF-α. And western blot analysis was performed to determine the translocation of GLUT4. Finally, effects of ginsenoside Re on NO production in 3T3-L1 adipocytes and in macrophages were investigated through measurement of nitrite concentration by Griess reagent.

Results

Ginsenoside Re induced adipogenesis of 3T3-L1 adipocytes by accumulating TG, increased glucose uptake and up-regulated PPAR-γ2, IRS-1, ap2 and adiponectin genes expressions. Meanwhile, Re also increased production and release of adiponectin. Although having no effects on GLUT4 gene expression, Re facilitated GLUT4 protein translocation to the membranes. In addition, Re inhibited the expression and release of TNF-α. Finally, Re did not show inhibitory effects on NO production both in 3T3-L1 cells stimulated by LPS, TNF-α and IFN-γ and in LPS-stimulated mouse peritoneal macrophages.

Conclusions

Ginsenoside Re exhibited the action of reducing insulin resistance through activation of PPAR-γ pathway by directly increasing the expressions of PPAR-γ2 and its responsive genes, adiponectin, IRS-1, ap2, inhibiting TNF-α production and facilitating the translocation of GLUT4 to promote glucose uptake and disposal in 3T3-L1 adipocytes.     

黄萸方对大鼠糖尿病早期肾脏保护作用的研究

目的:观察中药复方黄萸方对实验性糖尿病大鼠微量白蛋白尿的疗效。方法:采用高糖高脂喂饲加低剂量STZ建立伴胰岛素抵抗的大鼠2型糖尿病模型,给予黄萸方治疗12周,动态观察血糖及尿微量白蛋白等指标。结果:黄萸方可降低血糖、减少尿微量白蛋白、减轻肾脏肥大、改善尿多症状、降低血清甘油三酯水平,疗效优于血管紧张素Ⅱ受体拮抗剂(ARB)氯沙坦。结论:黄萸方可改善实验性大鼠2型糖尿病肾脏病变,主要是减少微量白蛋白尿的作用。     

肿瘤坏死因子-α诱导3T3-L1脂肪细胞胰岛素抵抗模型的建立

目的:应用肿瘤坏死因子d(TNF-α)诱导3T3-L1脂肪细胞,探讨建立可靠胰岛素抵抗(IR)细胞模型的方法.方法:3T3-L1前脂肪细胞经3-异丁基-1-甲基黄嘌呤、地塞米松、胰岛素诱导分化成3T3-L1脂肪细胞,将其与20,10,5μg·L-1TNF-α共孵育,100 nmol·L-1胰岛素作用30 min刺激脂肪细胞糖转运.以葡萄糖氧化酶法测定培养基上清液葡萄糖含量,观察TNF-α对脂肪细胞糖摄取的影响,鉴定IR模型.结果:TNF-α抑制胰岛素诱导前、后的脂肪细胞糖转运,抑制作用呈剂量依赖性,其中20 μg·L-1TNF-α的抑制率分别为79.2％和81.4％(P＜0.05).结论:肿瘤坏死因子α可诱导3T3-L1脂肪细胞产生IR,这种细胞模型简便、可靠.     

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??OBJECTIVE To improve the water solubility of ginsenoside Rg3, using mesoporous silica nanoparticles MCM-41 loading ginsenoside Rg3 and study the mechanism of promoting drug absorption with human lung cancer cells A549 as a model. METHODS The mesoporous silica nanoparticles MCM-41, as a carrier, loading ginsenoside Rg3 by adsorption method. The morphology and particle size of MCM-41 were investigated by transmission electron microscopy (TEM) and laser particle size analyzer. The solid state characterization of ginsenoside Rg3 were investigated by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy method (FTIR), respectively. In vitro dissolution experiments investigated the dissolution rate of ginsenoside Rg3. Cytotoxicity assay and cell uptake experiments explored the effect of the administration system of A549 cells and the mechanism of inhibiting cell proliferation. RESULTS We have been successfully prepared the mesoporous silica nanoparticles MCM-41. In vitro dissolution experiments showed that MCM-41 can significantly improve the dissolution rates of ginsenoside Rg3. Administration system can be uptaked into A549 cells and inhibit cell proliferation. CONCLUSION The mesoporous silica nanoparticles MCM-41 has a good solubilization effect for ginsenoside Rg3, and MCM-41 has potential as a carrier for the treatment of lung cancer.     

复方调脂降糖汤治疗糖尿病代谢综合征的临床观察

目的观察复方调脂降糖汤治疗2型糖尿病（T2DM）代谢综合征（MS）的临床疗效。方法将符合入选标准的134例以2型糖尿病代谢综合征患者分为治疗组（67例）和对照组（67例）。对照组常规给予降糖、降压药物,使血糖、血压达到稳定且符合入组条件,治疗组在对照组用药基础上给予复方调脂降糖汤口服。检测两组治疗前及治疗4周、8周后空腹血糖、血脂、血清胰岛素、糖化血红蛋白、腰围和减轻体重等指标。结果两组治疗8周后,在三酰甘油、高密度脂蛋白、体重、空腹血糖、空腹胰岛素、胰岛素抵抗指数、腰围等指标较治疗前有明显改善（P〈0.05）,其中治疗组低密度脂蛋白、体重、空腹胰岛素、胰岛素抵抗指数等指标优于对照组（P〈0.05）。结论复方调脂降糖汤具有明显改善胰岛素抵抗作用,同时可以降糖、调脂、减小腰围和体重,缓解MS的多种危害因素。     

Insulin‐Sensitizing and Beneficial Lipid‐Metabolic Effects of the Water‐Soluble Melanin Complex Extracted from Inonotus obliquus

Inonotus obliquus has been traditionally used for treatment of metabolic diseases; however, the mechanism remains to be elucidated. In this study, we found that the water‐soluble melanin complex extracted from I. obliquus improved insulin sensitivity and reduced adiposity in high fat (HF)‐fed obese mice. When the melanin complex was treated to 3T3‐L1 adipocytes, insulin‐stimulated glucose uptake was increased significantly, and its phosphoinositide 3‐kinase‐dependent action was proven with wortmannin treatment. Additionally, dose‐dependent increases in Akt phosphorylation and glucose transporter 4 translocation into the plasma membrane were observed in melanin complex‐treated cells. Adiponectin gene expression in 3T3‐L1 cells incubated with melanin complex increased which was corroborated by increased AMP‐activated protein kinase phosphorylation in HepG2 and C2C12 cells treated with conditioned media from the 3T3‐L1 culture. Melanin complex‐treated 3T3‐L1 cells showed no significant change in expression of several lipogenic genes, whereas enhanced expressions of fatty acid oxidative genes were observed. Similarly, the epididymal adipose tissue of melanin complex‐treated HF‐fed mice had higher expression of fatty acid oxidative genes without significant change in lipogenic gene expression. Together, these results suggest that the water‐soluble melanin complex of I. obliquus exerts antihyperglycemic and beneficial lipid‐metabolic effects, making it a candidate for promising antidiabetic agent. Copyright © 2014 John Wiley & Sons, Ltd.