虫草头孢提取物Fr.8组分对HepG-2胰岛素抵抗的改善作用

为探讨虫草头孢正己烷分离组分Fr.8对高胰岛素诱导的HepG-2细胞胰岛素抵抗的改善作用,作者建立了稳定的胰岛素抵抗细胞模型,并检测了Fr.8组分对胰岛素抵抗细胞(HepG-2/IR)的葡萄糖消耗、葡萄糖摄取及相关基因转录和蛋白质表达的影响。结果显示,5μmol/L胰岛素是诱导细胞成为HepG-2/IR的最佳作用浓度;Fr.8组分在无细胞毒性范围内可显著增加HepG-2/IR对葡萄糖的消耗及摄取;Fr.8(25μg/mL)可明显上调IR、IRS1、IRS2、Glut2、AMPKαmRNA的表达水平,并上调IR、IRS、Glut2、p-AMPKα、p-AKT蛋白质的表达。研究表明,虫草头孢Fr.8可改善HepG-2胰岛素抵抗,其机制可能与胰岛素受体及底物、葡萄糖转运蛋白2、pAMPKα和p-AKT蛋白的激活有关。     

紫色马铃薯花色苷改善HepG2细胞胰岛素抵抗模型糖代谢的机制

目的:观察紫色马铃薯花色苷对HepG2细胞胰岛素抵抗模型糖代谢的作用并对其机制进行初探。方法:以高浓度葡萄糖培养基为诱导因素诱导HepG2细胞建立胰岛素抵抗细胞模型,通过葡萄糖氧化酶法、四唑盐比色实验(MTT)和蛋白质印迹法(Western blot)检测紫色马铃薯花色苷对胰岛素抵抗细胞模型的葡萄糖消耗量、细胞存活率和胰岛素信号通路的蛋白表达的影响。结果:与空白对照组相比,当诱导培养基中葡萄糖浓度为50 mmol/L时吸光度的差值最大,所以选50 mmol/L的葡萄糖培养基来建立胰岛素抵抗细胞模型;花色苷的处理胰岛素抵抗细胞的浓度为40~100 μg/mL时,葡萄糖消耗量可高达19.55 mmol/L显著(p<0.05)高于模型对照组;花色苷浓度为40~100 μg/mL时细胞存活率基本上可以保持在80%,细胞毒性较小;花色苷可以调节因高浓度葡萄糖诱导而导致的IR、IRS-1、IRS-2水平下降的情况,降低p-IRS-1的表达水平,还可以阻止GLUT-2水平的降低。结论:紫色马铃薯花色苷可以改善HepG2细胞胰岛素抵抗模型的胰岛素信号通路抑制的情况,改善胰岛素抵抗模型的糖代谢。     

壳寡糖改善HepG2细胞胰岛素抵抗作用及机制研究

壳寡糖(chitooligosaccharides, COS)是一种具有多种生物活性的低聚寡糖,该文探究了COS对HepG2细胞胰岛素抵抗的影响作用。通过胰岛素诱导HepG2细胞建立胰岛素抵抗模型,评估COS及其单体组分(聚合度2～4)对其缓解作用。结果显示,COS显著提高产生胰岛素抵抗HepG2细胞的葡萄糖消耗量,促进其葡萄糖代谢。进一步评估不同聚合度的COS单体发现,壳二糖和壳四糖对胰岛素抵抗的肝细胞无显著改善效果,而壳三糖显著提高胰岛素抵抗HepG2细胞的葡萄糖消耗量。另外,COS及壳三糖显著提高胰岛素受体(insulin receptor, IR)、胰岛素受体底物1(insulin receptor substrate 1, IRS-1)、葡萄糖转运蛋白4(glucose transporter 4, GLUT4)蛋白水平,活化蛋白激酶B(protein kinase B, PKB/Akt)以及改善相关基因转录水平。综上,COS通过介导Akt/GLUT4通路改善HepG2细胞的胰岛素抵抗,壳三糖在促进糖代谢中表现最优。     

蜂胶黄酮及其功效成分对脂代谢的调节作用

目的 研究蜂胶黄酮及其功效成分对脂质代谢紊乱的调节作用及机制.方法 建立高脂血症大鼠模型,研究蜂胶黄酮对大鼠血脂水平及脂质代谢关键酶活性的影响;同时,在体外观察蜂胶黄酮功效成分对胰岛素抵抗的改善作用.结果 蜂胶黄酮可显著降低高脂血症大鼠的血清甘油三酯(TG)和总胆固醇(TC)水平(P＜0.05);在体外试验中,蜂胶黄酮可上调肝酯酶(HL)和7α-羟化酶(7CYP7A1)的活性水平(P＜0.05);在胰岛素抵抗的L6肌管细胞中,蜂胶黄酮功效成分7-甲基白杨素、槲皮素-3-O-新橙皮糖苷和咖啡酸可明显提高细胞对葡萄糖的消耗(P ＜0.05);7-甲基白杨素0.4 μg/ml以及槲皮素-3-O-新橙皮糖苷10 μg/ml能显著降低L6肌管细胞对游离脂肪酸(FFA)的摄取.结论 蜂胶黄酮可有效改善脂质代谢紊乱,其作用机制可能是增强脂质代谢关键酶活性以及改善胰岛素抵抗状况.     

蓝莓花色苷提取物干预人肝癌细胞对葡萄糖消耗的作用研究

探究蓝莓花色苷提取物对胰岛素抵抗的人肝癌细胞HepG2细胞对葡萄糖消耗的干预作用。利用MTT实验筛选得到3个品种蓝莓花色苷提取物的最适作用浓度;筛选胰岛素和葡萄糖诱导HepG2细胞产生胰岛素抵抗的最佳浓度;以MTT矫正细胞数量,用葡萄糖氧化酶法检测细胞培养基中葡萄糖的变化来研究蓝莓花色苷提取物的对细胞胰岛素抵抗的干预作用。北陆花色苷提取物在低于200μg/m L的浓度时,灿烂和园蓝花色苷提取物在低于100μg/m L的浓度时,对HepG2细胞活力无明显影响;以诱导剂胰岛素的浓度为1×10-8mol/L,孵育24h作为诱导条件,其模型效果较佳、对细胞活力改变小且稳定性好;3个品种的蓝莓花色苷提取物在7.8125～31.25μg/m L浓度时,可不同程度促进正常HepG2细胞和胰岛素抵抗的HepG2细胞对葡萄糖的消耗量,且与剂量成正比关系,在31.25μg/m L达到促进最大值,与模型组比较均有极显著差异,糖消耗量分别增加了60%、65%和88%。三个品种的蓝莓花色苷提取物均能较好的预防和改善胰岛素抵抗HepG2细胞对葡萄糖的利用。     

核桃多肽对高糖诱导HepG2胰岛素抵抗模型的影响

目的:探究核桃多肽在细胞水平上的降糖作用机制,为核桃资源开发利用提供科学依据。方法:在实验室提取的HT多肽,分离纯化HT-1、HT-2的基础上,通过GLUT4转膜活性筛选,L6肌管细胞葡萄糖摄取活性筛选以及高糖诱导HepG2细胞模型胰岛素抵抗实验,探究核桃多肽的降糖生物活性及降糖作用机制。结果:HT多肽、HT-1、HT-2均有一定的促GLUT4转膜活性,其中量效曲线趋势分布较好的为HT-2,15min开始响应,30min达峰值,在25min细胞膜上GLUT4增加1倍;葡萄糖摄取活性都较好,摄取率分别为1.16、1.06和1.36;IRβ、IRS-1蛋白、GLUT2蛋白的表达水平与HT-2呈浓度依赖性增加,表明HT-2通过胰岛素信号传导途径改善葡萄糖代谢。结论:HT多肽、HT-1、HT-2的降糖活性都较好,其中HT-2效果明显,且是通过胰岛素信号传导途径改善葡萄糖代谢。     

D-松醇复配Mn2+对HepG2细胞胰岛素抵抗的调节及其作用机制

采用胰岛素诱导HepG2细胞建立胰岛素抵抗模型(IR),研究D-松醇复配Mn2+对细胞葡萄糖消耗量和糖原合成量的影响。实时荧光全定量分析(RT-PCR)实验检测AMPK信号通路相关基因mRNA表达水平。结果表明当胰岛素浓度为1×10-3 mmol/L,作用时间为36 h时,细胞葡萄糖消耗量达到最低,产生最大的胰岛素抵抗效应。与模型对照组相比,当D-松醇浓度为100 mg/L,复配MnSO₄为10 mg/L时,葡萄糖消耗量和糖原含量均极显著升高(p<0.01)。此外,复配组AMPKα-1、AMPKα-2和GLUT4基因表达水平均显著上调(p<0.05),G6Pase基因mRNA表达水平显著下调(p<0.05)。D松醇复配Mn2+可显著促进胰岛素抵抗细胞葡萄糖的利用,增加糖原合成,其作用机制可能涉及AMPK参与的抑制糖异生等生化调控过程起到降血糖作用。     

人参皂苷F2通过PI3K/Akt途径改善3T3-L1脂肪细胞胰岛素抵抗

该研究探讨了人参皂苷F2对3T3-L1脂肪细胞胰岛素抵抗的影响及其机制。将3T3-L1前脂肪细胞诱导分化成熟后,用1 μmol/L地塞米松处理48 h,建立胰岛素抵抗模型。用10 μmol/L的罗格列酮（阳性对照）和25、50、100 μmol/L人参皂苷F2处理胰岛素抵抗细胞12 h,检测细胞对2-NBDG的摄取。实验结束后用RT-qPCR检测各组细胞中葡萄糖转运蛋白4（GLUT-4）和胰岛素底物受体1（IRS-1）mRNA相对表达量,并利用Western blot检测PI3K/Akt信号通路中蛋白表达及其磷酸化水平。结果表明：与模型组相比,25、50、100 μmol/L人参皂苷F2均能促进胰岛素抵抗3T3-L1脂肪细胞对2-NBDG的摄取,分别增加了12.58%、29.07%和34.62%（p<0.05）;人参皂苷F2作用12 h后,GLUT-4和IRS-1 mRNA相对表达量以及PI3K、Akt的磷酸化水平显著提高（p<0.01）。该研究表明人参皂苷F2可通过促进胰岛素抵抗3T3-L1脂肪细胞中GLUT-4和IRS-1mRNA相对表达,增加PI3K和Akt蛋白磷酸化,从而激活PI3K/Akt信号通路,改善其糖代谢和胰岛素抵抗。     

槲皮素-3-o-新橙皮糖苷改善 L6 细胞胰岛素抵抗及其作用机制

目的 观察槲皮素-3-o-新橙皮糖苷对 L6 肌管细胞胰岛素抵抗模型葡萄糖消耗; 脂肪酸消耗以及对 PPARα、PPARγ、GLUT4 表达量的调节作用及其作用机制。方法 以 250 μmol/L 的脂肪酸诱导形成 L6 肌管细胞胰岛素抵抗模型, 以槲皮素-3-o-新橙皮糖苷干预24 h后, 葡萄糖氧化酶法检测葡萄糖消耗量, 气相色谱法(GC)检测脂肪酸消耗量, Western-blot方法检测细胞中葡萄糖转运蛋白4(GLUT4)以及PPARα、 PPARγ的表达量。结果 槲皮素-3-o-新橙皮糖苷处理可提高 L6 细胞对葡萄糖的消耗(P<0.01), 降低细胞脂肪酸摄入(P<0.05), 上调 GLUT4 和 PPARγ 蛋白表达量(分别为 P<0.01 和 P<0.05), 但对 PPARα 的表达量无明显影响。结论 槲皮素-3-o-新橙皮糖苷可提高 L6 细胞胰岛素抵抗模型葡萄糖消耗量, 降低脂肪酸摄入, 调节 PPARγ、GLUT4 的表达, 这些可能是受试物缓解胰岛素抵抗的机制之一。     

山茱萸中马钱苷和莫诺苷对HepG2细胞及其胰岛素抵抗模型的影响研究

本文通过微波辅助提取、有机溶剂萃取、大孔树脂、制备色谱和HPLC等方法对山茱萸活性成分进行分离、纯化和鉴定,得到马钱苷和莫诺苷两种主要成分。考察了正丁醇30%乙醇洗脱相(Fr.Bu-2)、马钱苷、莫诺苷对Hep G2细胞及其胰岛素抵抗模型摄取葡萄糖的影响以及对Hep G2细胞的毒性作用,结果发现,马钱苷和莫诺苷对Hep G2细胞增殖没有显著影响;Fr.Bu-2、马钱苷和莫诺苷均能显著促进Hep G2细胞葡萄糖摄取(GU),其中马钱苷促进作用最强,且呈剂量依赖性,在0.5 mg/mL浓度时,马钱苷组和莫诺苷组GU分别是对照组的3.24倍和1.64倍;此外,Fr.Bu-2、马钱苷、莫诺苷在高浓度(≥0.1 mg/mL)下均能显著促进胰岛素抵抗模型细胞GU,在0.5 mg/mL浓度时,马钱苷组和莫诺苷组的模型细胞GU分别为对照组的1.76倍和1.27倍。这些结果说明Fr.Bu-2、马钱苷和莫诺苷均能通过促进Hep G2细胞及其胰岛素抵抗模型摄取葡萄糖发挥降血糖作用。     

Myricetin attenuates hyperinsulinemia-induced insulin resistance in skeletal muscle cells

Previous studies have shown that hyperinsulinemia is not only a marker of insulin resistance, but also the causative factor of peripheral tissue insulin resistance. It also has been suggested that prolonged high-dose insulin treatment can mimic the effects of hyperinsulinemia and exacerbate insulin resistance in skeletal muscle cells. However, how to prevent or reverse insulin resistance induced by hyperinsulinemia remains largely unclear. In the past few decades, the use of myricetin as an anti-diabetic agent has gained much attention, but little information is available regarding the effects of myricetin on glucose uptake and hyperinsulinemia-induced insulin resistance in skeletal muscle cells. The present study focuses on the effect of myricetin on insulin signaling in skeletal muscle cell line C2C12 myotubes. Initially, the effect of myricetin under normal condition was determined. We found that myricetin’s enhancement in glucose uptake coincided with both protein kinase B (Akt) and AMP-activated protein kinase (AMPK) activities. After that, the role of hyperinsulinemia was investigated. It was showed that prolonged high-dose insulin treatment inhibited both Akt and AMPK activities. As the results, the low-dose insulin stimulation of glucose uptake was inhibited by hyperinsulinemia. However, the treatment of myricetin improved low-dose insulin-stimulated glucose uptake in the hyperinsulinemic state, and this effect essentially depended on the AMPK signal pathway. Together, our data suggest a putative link between hyperinsulinemia and insulin resistance in C2C12 myotubes, and the myricetin treatment stimulates glucose uptake and attenuates insulin resistance.     

Crosstalk between the AMP-activated kinase and insulin signaling pathways rescues murine blastocyst cells from insulin resistance

Maternal insulin resistance results in poor pregnancy outcomes. In vivo and in vitro exposure of the murine blastocyst to high insulin or IGF1 results in the down-regulation of the IGF1 receptor (IGF1R). This in turn leads to decreased glucose uptake, increased apoptosis, as well as pregnancy resorption and growth restriction. Recent studies have shown that blastocyst activation of AMP-activated protein kinase (AMPK) reverses these detrimental effects; however, the mechanism was not clear. The objective of this study was to determine how AMPK activation rescues the insulin-resistant blastocyst. Using trophoblast stem (TS) cells derived from the blastocyst, insulin resistance was recreated by transfecting with siRNA to Igf1r and down-regulating expression of the protein. These cells were then exposed to AMPK activators 5-aminoimidazole-4-carboxamide riboside and phenformin, and evaluated for apoptosis, insulin-stimulated 2-deoxyglucose uptake, PI3-kinase activity, and levels of phospho-AKT, phospho-mTor, and phospho-70S6K. Surprisingly, disrupted insulin signaling led to decreased AMPK activity in TS cells. Activators reversed these effects by increasing the AMP/ATP ratio. Moreover, this treatment increased insulin-stimulated 2-deoxyglucose transport and cell survival, and led to an increase in PI3-kinase activity, as well as increased P-mTOR and p70S6K levels. This study is the first to demonstrate significant crosstalk between the AMPK and insulin signaling pathways in embryonic cells, specifically the enhanced response of PI3K/AKT/mTOR to AMPK activation. Decreased insulin signaling also resulted in decreased AMPK activation. These findings provide mechanistic targets in the AMPK signaling pathway that may be essential for improved pregnancy success in insulin-resistant states.     

Hydro‐ethanolic extract of cashew tree (Anacardium occidentale) nut and its principal compound,anacardic acid,stimulate glucose uptake in C2C12 muscle cells

Scope: Products of cashew tree (Anacardium occidentale) are used in traditional medicine for various ailments, including diabetes. Methods and results: The anti‐diabetic properties of cashew plant parts were studied using differentiated C2C12 myoblasts (myotubes) and rat liver mitochondria. Hydroethanolic extract of cashew seed (CSE) and its active component, anacardic acid (AA), stimulated glucose transport into C2C12 myotubes in a concentration‐dependent manner. Extracts of other parts (leaves, bark and apple) of cashew plant were inactive. Significant synergistic effect on glucose uptake with insulin was noticed at 100 μg/mL CSE. CSE and AA caused activation of adenosine monophosphate‐activated protein kinase in C2C12 myotubes after 6 h of incubation. No significant effect was noticed on Akt and insulin receptor phosphorylation. Both CSE and AA exerted significant uncoupling of succinate‐stimulated respiration in rat liver mitochondria. Conclusion: Activation of adenosine monophosphate‐activated protein kinase by CSE and AA likely increases plasma membrane glucose transporters, resulting in elevated glucose uptake. In addition, the dysfunction of mitochondrial oxidative phosphorylation may enhance glycolysis and contribute to increased glucose uptake. These results collectively suggest that CSE may be a potential anti‐diabetic nutraceutical.     

Epigallocatechin gallate (EGCG) attenuates high glucose-induced insulin signaling blockade in human hepG2 hepatoma cells

Insulin resistance is the primary characteristic of type 2 diabetes which as a result of insulin signaling defects. It has been suggested that the tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) displays some antidiabetic effects, but the mechanism for EGCG insulin-enhancing effects is incompletely understood. In the present study, the investigations of EGCG on insulin signaling are performed in insulin-responsive human HepG2 cells cotreated with high glucose. We found that the high glucose condition causes significant increasing Ser307 phosphorylation of insulin receptor substrate-1 (IRS-1), leading to reduce insulin-stimulated phosphorylation of Akt. As the results, the insulin metabolic effects of glycogen synthesis and glucose uptake are inhibited by high glucose. However, the treatment of EGCG improves insulin-stimulated downsignaling by reducing IRS-1 Ser307 phosphorylation. Furthermore, we also demonstrated these EGCG effects are essential depends on the 5'-AMP-activated protein kinase (AMPK) activation. Together, our data suggest a putative link between high glucose and insulin resistance in HepG2 cells, and the EGCG treatment attenuates insulin signaling blockade by reducing IRS-1 Ser307 phosphorylation through the AMPK activation pathway.     

Saffron (Crocus sativus L.) increases glucose uptake and insulin sensitivity in muscle cells via multipathway mechanisms

Saffron (Crocus sativus Linn.) has been an important subject of research in the past two decades because of its various biological properties, including anti-cancer, anti-inflammatory, and anti-atherosclerotic activities. On the other hand, the molecular bases of its actions have been scarcely understood. Here, we elucidated the mechanism of the hypoglycemic actions of saffron through investigating its signaling pathways associated with glucose metabolism in C₂C₁₂ skeletal muscle cells. Saffron strongly enhanced glucose uptake and the phosphorylation of AMPK (AMP-activated protein kinase)/ACC (acetyl-CoA carboxylase) and MAPKs (mitogen-activated protein kinases), but not PI 3-kinase (Phosphatidylinositol 3-kinase)/Akt. Interestingly, the co-treatment of saffron and insulin further improved the insulin sensitivity via both insulin-independent (AMPK/ACC and MAPKs) and insulin-dependent (PI 3-kinase/Akt and mTOR) pathways. It also suggested that there is a crosstalk between the two signaling pathways of glucose metabolism in skeletal muscle cells. These results could be confirmed from the findings of GLUT4 translocation. Taken together, AMPK plays a major role in the effects of saffron on glucose uptake and insulin sensitivity in skeletal muscle cells. Our study provides important insights for the possible mechanism of action of saffron and its potential as a therapeutic agent in diabetic patients.     

Stimulation of AMP‐activated protein kinase and enhancement of basal glucose uptake in muscle cells by quercetin and quercetin glycosides,active principles of the antidiabetic medicinal plant Vaccinium vitis‐idaea

Several medicinal plants that stimulate glucose uptake in skeletal muscle cells were identified from among species used by the Cree of Eeyou Istchee of northern Quebec to treat symptoms of diabetes. This study aimed to elucidate the mechanism of action of one of these products, the berries of Vaccinium vitis idaea, as well as to isolate and identify its active constituents using a classical bioassay‐guided fractionation approach. Western immunoblot analysis in C2C12 muscle cells revealed that the ethanol extract of the berries stimulated the insulin‐independent AMP‐activated protein kinase (AMPK) pathway. The extract mildly inhibited ADP‐stimulated oxygen consumption in isolated mitochondria, an effect consistent with metabolic stress and the ensuing stimulation of AMPK. This mechanism is highly analogous to that of Metformin. Fractionation guided by glucose uptake activity resulted in the isolation of ten compounds. The two most active, quercetin‐3‐O‐glycosides, enhanced glucose uptake by 38–59% (50 μM; 18 h treatment) in the absence of insulin. Quercetin aglycone, a minor constituent, stimulated uptake by 37%. The quercetin glycosides and the aglycone stimulated the AMPK pathway at concentrations of 25–100 μM, but only the aglycone inhibited ATP synthase in isolated mitochondria (by 34 and 79% at 25 and 100 μM, respectively). This discrepancy suggests that the activity of the glycosides may require hydrolysis to the aglycone form. These findings indicate that quercetin and quercetin 3‐O‐glycosides are responsible for the antidiabetic activity of V. vitis crude berry extract mediated by AMPK. These common plant products may thus have potential applications for the prevention and treatment of insulin resistance and other metabolic diseases.     

糖苷结构对苦荞黄酮促进葡萄糖在C2C12小鼠骨骼肌细胞中摄取作用的影响

苦荞是芦丁含量最高的粮食作物,但不同的加工过程会导致芦丁降解为单糖苷结构的异槲皮素及其前体槲皮素,进而影响生物活性。本研究比较芦丁及其降解产物（槲皮素、异槲皮素）这三类含有不同糖苷结构的黄酮在C2C12小鼠骨骼肌细胞中促进葡萄糖摄取的功效差异,并探究其作用机制。研究结果表明,苦荞与水接触会导致苦荞中的核心黄酮组分-芦丁降解为槲皮素。芦丁及其降解产物（槲皮素、异槲皮素）均能有效促进C2C12细胞对葡萄糖的摄取,作用顺序为:槲皮素>异槲皮素>芦丁。糖苷键的增加会降低槲皮素促进骨骼肌细胞糖摄取的效果。芦丁和异槲皮素不能激活胰岛素依赖型信号通路中的IRS-1表达及AKT的磷酸化,但高浓度下（400 μmol/L）,芦丁和异槲皮素可以通过非胰岛素依赖型的信号通路中的p-AMPK/p-ACC促进葡萄糖摄取作用,且异槲皮素的作用大于芦丁。槲皮素虽然抑制了IRS-1的表达及AKT的磷酸化,但槲皮素通过AMPK/ACC的磷酸化显著了促进C2C12细胞对葡萄糖的摄取。本研究揭示芦丁及其降解产物在细胞水平上的降血糖作用及机理的差异,对于充分理解苦荞黄酮降血糖机制提供了科学依据。     

Tea catechins modulate the glucose transport system in 3T3-L1 adipocytes

In this study, we investigated the effects of tea catechins on the translocation of glucose transporter (GLUT) 4 in 3T3-L1 adipocytes. We found that the ethyl acetate fraction of green tea extract, containing abundant catechins, most decreased insulin-induced glucose uptake activity in 3T3-L1 cells. When the cells were treated with 50 μM catechins in the absence or presence of insulin for 30 min, nongallate-type catechins increased glucose uptake activity without insulin, whereas gallate-type catechins decreased insulin-induced glucose uptake activity. (-)-Epicatechin (EC) and (-)-epigallocatechin (EGC), nongallate-type catechins, increased glucose uptake activity in the dose- and time-dependent manner, whereas (-)-catechin 3-gallate (Cg) and (-)-epigallocatechin 3-gallate (EGCg), gallate-type catechins, decreased insulin-induced glucose uptake activity in the dose- and time-dependent manner. When the cells were treated with 50 μM catechins for 30 min, EC and EGC promoted GLUT4 translocation, whereas Cg and EGCg decreased the insulin-induced translocation in the cells. EC and EGC increased phosphorylation of PKCλ/ζ without phosphorylation of insulin receptor (IR) and Akt. Wortmannin and LY294002, inhibitors for phosphatidylinositol 3'-kinase (PI3K), decreased EC- and EGC-induced glucose uptake activity in the cells. Cg and EGCg decreased phosphorylation of PKCλ/ζ in the presence of insulin without affecting insulin-induced phosphorylation of IR, and Akt. Therefore, EC and EGC promote the translocation of GLUT4 through activation of PI3K, and Cg and EGCg inhibit insulin-induced translocation of GLUT4 by the insulin signaling pathway in 3T3-L1 cells.     

Ethylacetate extracts of the muscles of Anguilla japonica suppress glucose levels in db/db mice via activation of AMP-activated protein kinase

Hypoglycemic effects of ethylacetate extracts of Anguilla japonica (EMA) muscles in db/db mice were investigated. To understand the mechanism responsible for the hypoglycemic effects of EMA, the effects of EMA on AMP-activated protein kinase (AMPK) activation in L6 myotubes and in vivo using type II diabetic db/db mice were analyzed. In L6 myotubes, the phosphorylation degrees of AMPK and acetyl-CoA carboxylase (ACC) were markedly increased and glucose uptake was significantly (p<0.001) increased by EMA, compared with untretaed L6 myotubes. However, in L6 myotubes, these effects were abolished by compound C, an AMPK inhibitor. Moreover, EMA significantly reduced non-fasting blood glucose and serum insulin levels, and strongly induced AMPK phosphorylation in skeletal muscle tissues of db/db mice. EMA regulates glucose levels in L6 myotubes and in diabetic mice by activation of AMPK. Beneficial effects for diabetes treatment are indicated.