吡格列酮对高脂喂养大鼠骨骼肌组织脂质异位沉积的影响

目的:观察吡格列酮(Pio)对高脂喂养大鼠骨骼肌组织脂质异位沉积的影响。方法:30只Wistar大鼠平均分为对照组、胰岛素抵抗组和吡格列酮干预组,对照组给予基础饲料,其余2组均给予高脂饲料喂养,其中吡格列酮干预组同时给予吡格列酮20 mg·kg^-1·d^-1灌胃,各组均喂养16周后检测各组大鼠血游离脂肪酸(FFA)水平及骨骼肌组织中三酰甘油(TG)含量,同时应用蛋白免疫印迹法检测骨骼肌组织一磷酸腺苷活化蛋白激酶α(AMPKα)磷酸化水平。结果:与对照组比较,胰岛素抵抗组大鼠胰岛素敏感性显著降低,血FFA水平及骨骼肌组织TG含量增高,骨骼肌组织中AMPKα磷酸化水平降至对照组水平的52.9%;与胰岛素抵抗组比较,吡格列酮干预组大鼠胰岛素敏感性明显提高,血FFA水平及骨骼肌组织TG含量显著下降,骨骼肌组织中AMPKα磷酸化水平显著提高至对照组的81.3%。但是与对照组比较,吡格列酮干预组大鼠血FFA水平及骨骼肌组织TG含量仍然较高,而且胰岛素敏感性及骨骼肌组织中AMPKα磷酸化水平仍然显著降低。结论:高脂饮食诱导胰岛素抵抗,吡格列酮干预可以通过降低血FFA水平及减轻骨骼肌组织脂质异位沉积改善其胰岛素抵抗。     

苯氧异丁酸类化合物的合成及其体外抗糖尿病活性

目的设计及合成新型苯氧异丁酸类抗糖尿病化合物。方法关键步骤采用亲核取代反应或Mitsunobu缩合反应把亲脂性片段和酸性片段连接成一体，共合成了8个新目标物。用核磁共振、红外、质谱进行结构确认。结果体外胰岛素增敏活性测试(3T3-L1脂肪细胞)结果显示，分别将罗格列酮、吡格列酮、目标物A和B加入已经存在胰岛素抵抗脂肪细胞培养液中，用GOD-POD方法分析得到上清液葡萄糖浓度分别为5.942，6.339，6.226和6.512 mmol·L^-1。结论目标物A在胰岛素抵抗实验(3T3-L1脂肪细胞)中抗糖尿病活性介于市售PPARγ激动剂罗格列酮和吡格列酮之间，而目标物B的活性略低于吡格列酮。     

吡格列酮降低胰岛素抵抗状态下的氧化应激水平

目的：探讨吡格列酮对胰岛素抵抗状态下的氧化应激水平的影响。方法：分别用TNF—α（4ng／mL）和高浓度胰岛素（10^-7mol／L）刺激人肝癌细胞HepG2,建立胰岛素抵抗细胞模型。MTT法观察细胞毒性作用;氧化酶法检测细胞培养液中的葡萄糖浓度;用DCF—DA探针标记,流式细胞仪检测细胞内活性氧的水平;免疫荧光检测NF—κB核转位。结果：TNF—α和高浓度胰岛素刺激HepG2后,导致葡萄糖摄取障碍,细胞培养液上清中葡萄糖浓度较对照组显著升高,同时细胞内活性氧的水平较对照组也显著升高。吡格列酮显著改善胰岛素抵抗状态,同时显著降低细胞内氧化应激的水平。吡格列酮还能逆转TNF—α和高浓度胰岛素引起的NF—κB核转位。结论：吡格列酮能抑制NF—κB核转位,降低氧化应激水平,改善胰岛素抵抗状态。     

吡格列酮对胰岛素抵抗HepG2细胞模型的药理学评价

目的应用高胰岛素诱导培养HepG2细胞,建立胰岛素抵抗的细胞模型。并探讨吡格列酮对该模型胰岛素敏感性和糖代谢的影响。方法将HepG2细胞置于5×10-7mol.L-1胰岛素培养液中16 h,采用3H-D-葡萄糖参入试验观察高胰岛素对HepG2细胞葡萄糖摄取率的影响。模型建立后,培养液中加入吡格列酮共同孵育,观察吡格列酮对胰岛素抵抗细胞模型葡萄糖摄取率和葡萄糖消耗量的影响。结果高胰岛素诱导培养的HepG2细胞葡萄糖参入率明显低于未用高胰岛素诱导的HepG2细胞(对照细胞)。将高胰岛素诱导培养的HepG2细胞置于不含胰岛素的培养液中60 h,其细胞葡萄糖摄取率仍明显低于对照细胞。含有吡格列酮(浓度为1×10-6~1×10-4mol.L-1)的胰岛素抵抗HepG2细胞的葡萄糖参入率与葡萄糖消耗量明显高于不含吡格列酮的胰岛素抵抗HepG2细胞(P<0.01)。结论将HepG2置于5×10-7mol.L-1胰岛素环境中16 h,该细胞对胰岛素的生物学效应产生抵抗,其胰岛素抵抗状态可维持60 h。该方法较为简便、易行、重复性好、成功率高,可广泛用于胰岛素抵抗的研究。吡格列酮能增加胰岛素抵抗模型细胞的胰岛素敏感性,并能明显改善糖代谢。     

吡格列酮对高脂喂养SD大鼠visfatin蛋白表达的影响

Visfatin由Fukuhlara等[1]2005 年发现,主要由内脏脂肪分泌.具有促进脂肪形成、降低血糖等类胰岛素作用,与肥胖、2型糖尿病有着密切联系.吡格列酮改善胰岛素抵抗的部分机制可能是通过调节脂肪因子的产生[2].本研究通过高脂喂养建立肥胖SD大鼠实验模型,用吡格列酮干预来观察其对visfatin表达的影响,探讨吡格列酮改善胰岛素敏感性的可能作用机制.     

吡格列酮治疗顽固性高血压病合并胰岛素抵抗患者的疗效观察

目的观察吡格列酮对顽固性高血压并胰岛素抵抗患者的疗效。方法选择46例顽固性高血压病合并胰岛素抵抗患者,随机分为两组,治疗组:每日加口服吡格列酮15mg,1次/d,共8周;对照组:原用的降压药不变,原生活方式不变。所有对象均于加用药前和加用药8周末检测血压、空腹血浆葡萄糖(FBG)、血清胰岛素(FINS),并作比较分析。结果治疗组患者的SBP、DBP、FPG、FINS和胰岛素抵抗指数(HOMA-IR)值,较治疗前均有显著性下降(P<0.01)。结论吡格列酮治疗顽固性高血压病合并胰岛素抵抗患者,不仅可使其空腹血糖明显下降,而且还具有降低患者血压和血清胰岛素水平,改善其胰岛素抵抗作用。     

吡格列酮对3T3-L1细胞分化过程中perilipin基因表达的影响

脂肪组织不仅仅是被动的能量储存器官，而且是能够分泌多种激素类物质的内分泌器。脂肪细胞分化及其调控失常与人类多种疾病如肥胖症、胰岛素抵抗及2型糖尿病等密切相关。Pefilipin（围脂素）是新近发现的特异表达于脂肪细胞和类固醇生成细胞脂滴表面的一种磷蛋白，其基因受PPARV（过氧化物酶体增殖物激活受体）调控。国外有报道认为，pefilipin基因有随3T3-L1脂肪细胞分化成熟表达水平逐渐升高的趋势，提示该基因可能与肥胖的病理生理过程有关。噻唑烷二酮类药物吡格列酮作为PPAR1配体，对肥胖患者的胰岛素抵抗状态有改善作用，而且具有促进脂肪细胞分化的作用特点；而目前国内有关吡格列酮对脂肪细胞中pefilipin基因表达的调节作用未见报道，因此本研究应用吡格列酮干预分化过程中3T3-L1细胞，观察3T3-L1细胞分化过程中pefilipin mRNA表达量的变化，探讨吡格列酮对perilipin mRNA表达的影响。     

吡格列酮和罗格列酮治疗2型糖尿病伴高脂血症的疗效比较

目的:观察吡格列酮和罗格列酮对2型糖尿病伴高脂血症患者血糖、胰岛素抵抗和血脂水平的影响。方法:将空腹血糖水平在7.0~13.0mmol.L-1和三酰甘油水平在1.7~6.9mmol.L-1的初诊2型糖尿病患者随机分为吡格列酮或罗格列酮组。吡格列酮每日30mg治疗24周;罗格列酮8mg治疗24周。结果:于24周时,吡格列酮和罗格列酮两组空腹血糖、餐后2h血糖、糖化血红蛋白、空腹胰岛素、胰岛素抵抗指数均较治疗前明显降低(P<0.01),两者之间降低的程度没有显著性差异(P>0.05)。吡格列酮组血三酰甘油和总胆固醇水平较治疗前明显降低(P<0.01),但罗格列酮组无明显变化(P>0.05)。两组的高密度脂蛋白胆固醇水平均比治疗前明显升高(P<0.05)和(P<0.01),但吡格列酮组升高的幅度大于罗格列酮组(P<0.05)。吡格列酮组的低密度脂蛋白胆固醇水平无明显变化(P>0.05),但罗格列酮组的低密度脂蛋白胆固醇水平比治疗前增高(P<0.05)。结论:吡格列酮和罗格列酮均能有效地控制2型糖尿病患者的血糖,降低胰岛素抵抗。但两者对血脂的影响明显不同,吡格列酮对血脂的影响明显优于罗格列酮。     

吡格列酮对高脂大鼠内脏肥胖与胰岛素抵抗的影响

目的：探讨环境因素引起的内脏性肥胖与胰岛素抵抗的关系,并观察吡格列酮对其的影响。方法：应用59%高脂饮食喂养大鼠4周制成胰岛素抵抗的动物模型后,给予吡格列酮干预4周,观察内脏肥胖对大鼠胰岛素敏感性的影响以及吡格列酮对其的干预。结果：经59%高脂饮食喂养8周后,模型对照组较正常对照组大鼠空腹血糖及胰岛素均明显增高,血脂、血清游离脂肪酸（FFA）亦明显增高。给予吡格列酮干预后药物干预组较模型对照组大鼠空腹血糖及胰岛素均明显减低,血脂、血清FFA亦明显减低。结论：高脂饮食可诱导内脏肥胖并导致胰岛素抵抗,而吡格列酮可干预此过程。     

吡格列酮改善胰岛素抵抗状态下氧化应激水平及分子机制探讨

目的：探讨吡格列酮（Pio）对胰岛素抵抗状态下的氧化应激水平的影响,并初步探讨Pio改善胰岛素抵抗作用的分子机制。方法：用TNF-α（4ng／mL）刺激人肝癌细胞HepG2,建立胰岛素抵抗细胞模型。MTT法观察细胞毒性作用;氧化酶法检测细胞培养液中的葡萄糖浓度;用DCFH-DA荧光探针标记,流式细胞仪检测细胞内活性氧（ROS）的水平;Western blotting检测氨基末端激酶（JNK）、磷酸化氨基末端激酶（p-JNK）和胰岛素受体底物1（IRS1）的表达。结果：TNF-α刺激HepG2后,导致葡萄糖摄取障碍,细胞培养液上清中葡萄糖浓度显著升高,细胞内ROS的水平显著升高,JNK被激活,IRS1的表达降低。Pio可显著降低ROS的水平,抑制JNK的磷酸化,促进IRS1的表达,改善胰岛素抵抗。结论：Pio通过降低氧化应激水平,抑制JNK信号通路,改善胰岛素抵抗状态。     

小檗碱与梓醇及其配伍对胰岛素抵抗3T3-L1脂肪细胞Glut-4、IRS-1、IRS-1 Ser307磷酸化蛋白表达的影响

目的：观察梓醇与小檗碱及其配伍对胰岛素抵抗3T3-L1脂肪细胞葡萄糖消耗及这一过程中葡萄糖转运子-4（Glut-4）、胰岛素受体底物-1（IRS-1）和胰岛素受体底物-1丝氨酸307（IRS-1Ser307）磷酸化蛋白表达的影响。方法：采用高糖联合高胰岛素诱导3T3-L1脂肪细胞产生胰岛素抵抗，分别给予小檗碱、梓醇、小檗碱＋梓醇、盐酸罗格列酮进行干预，以葡萄糖氧化酶法检测培养液中葡萄糖消耗量，以WesternBlot法检测蛋白的表达。结果：与模型组相比，小檗碱能增加培养液中葡萄糖的消耗（P〈0．01），但对Glut，4蛋白的表达无影响；梓醇、小檗碱＋梓醇均能显著增加培养液中葡萄糖的消耗（P〈0．01），并使细胞中Glut-4蛋白的表达增强（P〈0．05），且小檗碱＋梓醇组的效应优于梓醇组及小檗碱组；与模型组相比，小檗碱与梓醇及其配伍对IRS-1的表达没有显著性影响，但能降低IRS-1 Ser307磷酸化蛋白表达。结论：小檗碱、梓醇及其配伍能改善胰岛素抵抗3T3-L1脂肪细胞的胰岛素敏感性，其作用机制与罗格列酮不同。     

Cyanidin 3-glucoside protects 3T3-L1 adipocytes against H2O2- or TNF-alpha-induced insulin resistance by inhibiting c-Jun NH2-terminal kinase activation

Anthocyanins are naturally occurring plant pigments and exhibit an array of pharmacological properties. Our previous study showed that black rice pigment extract rich in anthocyanin prevents and ameliorates high-fructose-induced insulin resistance in rats. In present study, cyanidin 3-glucoside (Cy-3-G), a typical anthocyanin most abundant in black rice was used to examine its protective effect on insulin sensitivity in 3T3-L1 adipocytes exposed to H(2)O(2) (generated by adding glucose oxidase to the medium) or tumor necrosis factor alpha (TNF-alpha). Twelve-hour exposure of 3T3-L1 adipocytes to H(2)O(2) or TNF-alpha resulted in the increase of c-Jun NH(2)-terminal kinase (JNK) activation and insulin receptor substrate 1 (IRS1) serine 307 phosphorylation, concomitantly with the decrease in insulin-stimulated IRS1 tyrosine phosphorylation and cellular glucose uptake. Blocking JNK expression using RNA interference efficiently prevented the H(2)O(2)- or TNF-alpha-induced defects in insulin action. Pretreatment of cells with Cy-3-G reduced the intracellular production of reactive oxygen species, the activation of JNK, and attenuated H(2)O(2)- or TNF-alpha-induced insulin resistance in a dose-dependent manner. In parallel, N-acetyl-cysteine, an antioxidant compound, did not exhibit an attenuation of TNF-alpha-induced insulin resistance. Taken together, these results indicated that Cy-3-G exerts a protective role against H(2)O(2)- or TNF-alpha-induced insulin resistance in 3T3-L1 adipocytes by inhibiting the JNK signal pathway.     

Bilobalide abates inflammation,insulin resistance and secretion of angiogenic factors induced by hypoxia in 3T3-L1 adipocytes by controlling NF-κB and JNK activation

Obesity leads to inflammation and insulin resistance in adipose tissue. Hypoxia, observed in obese adipose tissue is suggested as a major cause of inflammation and insulin resistance in obesity. However, the role of hypoxia in adipose tissue during obesity and insulin resistance was not well established. Here we mainly explored the crosstalk between hypoxia induced inflammation, and insulin resistance and also secretion of angiogenic factors in 3T3-L1 adipocytes and possible reversal with bilobalide. Hypoxia for 24 h significantly (P ≤ 0.05) increased the secretion of MCP-1 (4.59 fold), leptin (2.96 fold) and reduced adiponectin secretion (2.93 fold). In addition, the mRNA level of resistin (6.8 fold) and TLR4 receptors (8.8 fold) was upregulated in hypoxic adipocytes. The release of inflammatory cytokines and expression of TLR4 receptors led to activation of JNK and NF-κB signalling. We further investigated the effects of JNK and NF-κB activation on insulin signalling receptors. The present study showed increased (P ≤ 0.05) serine 307 phosphorylation of IRS-1 (1.9 fold) and decreased expression of IRS-2 (0.53 fold) in hypoxic group showing hypoxia induced impairment in insulin signalling. Hypoxia significantly (P ≤ 0.05) increased basal glucose uptake (3.3 fold) as well as GLUT-1 expression in adipocytes indicating GLUT-1 mediated glucose uptake. Hypoxia for 24 h significantly increased (P ≤ 0.05) the expression of angiogenic factors. Bilobalide protected adipocytes from hypoxia induced inflammation and insulin resistance mainly by reducing inflammatory adipokine secretion, improving adiponectin secretion, reducing NF-κB/JNK activation, and inhibiting serine phosphorylation of IRS-1 receptors of insulin signalling pathway.     

Stimulation of glucose uptake and improvement of insulin resistance by aromadendrin

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.     

Bis(alpha-furancarboxylato)oxovanadium(IV) prevents and improves dexamethasone-induced insulin resistance in 3T3-L1 adipocytes

Previous studies showed that bis(alpha-furancarboxylato)oxovanadium(IV) (BFOV), an orally active anti-diabetic organic vanadium complex, could improve insulin resistance in animals with type 2 diabetes. The present study has been carried out to evaluate the effects of BFOV on insulin-resistant glucose metabolism using dexamethasone-treated 3T3-L1 adipocytes as an in-vitro model of insulin resistance. The results showed that BFOV, similar to vanadyl sulfate and rosiglitazone, caused a concentration-dependent increase in glucose consumption by insulin-resistant adipocytes. Moreover, BFOV enhanced the action of insulin and completely prevented the development of insulin resistance induced by dexamethasone, leading to glucose consumption equal to that by normal cells. In addition, dexamethasone reduced the mRNA expression of insulin receptor substrate 1 (IRS-1) and glucose transporter 4 (GLUT4) in 3T3-L1 adipocytes, while BFOV normalized the expression of IRS-1 and GLUT4. These findings suggest that BFOV prevents and improves dexamethasone-induced insulin resistance in 3T3-L1 adipocytes by enhancing expression of IRS-1 and GLUT4 mRNA.     

胰高血糖素样肽-1对胰岛素抵抗3T3-L1脂肪细胞脂肪酸代谢的作用及机制

目的研究胰高血糖素样肽-1(GLP 1)对胰岛素抵抗3T3 L1脂肪细胞脂肪酸代谢的作用及机制。方法采用高糖高胰岛素造成胰岛素抵抗3T3 L1脂肪细胞模型,通过ELISA及Western blot等方法观察GLP 1对此模型脂肪酸代谢的影响及机制。结果 ELISA结果显示,GLP 1对胰岛素抵抗3T3 L1脂肪细胞中游离脂肪酸(FFA)的含量影响与胰岛素相关:在有胰岛素(100 nmol.L-1)存在时,GLP 1可增加上清液中FFA含量;而无胰岛素存在时,GLP 1可减少上清液中FFA含量。GLP 1升高细胞中脂肪酸合成酶(FAS)表达量的作用也必须依赖胰岛素的存在。Western blot结果显示在有胰岛素存在时,GLP 1可促进蛋白激酶B(PKB)磷酸化;而无胰岛素存在时则无此作用。PKB磷酸化的抑制剂LY294002或Wortmannin可阻断胰岛素存在时GLP 1对PKB磷酸化的促进作用及对上清液FFA含量的升高作用。另外,在有(无)胰岛素存在时,GLP 1均可降低激素敏感性脂肪酶(HSL)的蛋白表达量。结论 GLP 1可增强胰岛素抵抗3T3 L1脂肪细胞对胰岛素的敏感性并降低HSL的含量;胰岛素可影响GLP 1对胰岛素抵抗3T3 L1脂肪细胞脂肪酸代谢的调节作用。     

Cyanidin-3-rutinoside increases glucose uptake by activating the PI3K/Akt pathway in 3T3-L1 adipocytes

In this study, the effect of cyanidin-3-rutinoside (C3R) on glucose uptake by 3T3-L1 adipocytes was studied. C3R significantly increased glucose uptake, which was associated with enhanced plasma membrane glucose transporter type 4 (PM-GLUT4) expression in 3T3-L1 adipocytes. The potentiating effect of C3R on glucose uptake and PM-GLUT4 expression was related to enhanced phosphorylation of insulin receptor substrate 1 (IRS-1) and Akt, as well as augmented activation of phosphatidylinositol-3-kinase (PI3K) in the insulin signaling pathway. C3R induced glucose uptake was inhibited only by the PI3K inhibitor, but not by an AMPK inhibitor in 3T3-L1 adipocytes. Therefore, C3R likely up-regulates glucose uptake and PM-GLUT4 expression in 3T3-L1 adipocytes by activating the PI3K/Akt pathways.     

Berberine reduces endoplasmic reticulum stress and improves insulin signal transduction in Hep G2 cells

Aim:

Endoplasmic reticulum (ER) stress plays an important role in the pathogenesis of insulin resistance and pancreatic β-cell dysfunction. The aim of this study is to investigate whether the insulin-sensitizing action of berberine is related to reducing ER stress.

Methods:

ER stress in cultured Hep G2 cells was induced with tunicamycin. Cells were pretreated with berberine in combination with or without insulin. The concentration of glucose was measured by glucose oxidase method. The molecular markers of ER stress, including ORP150, PERK, and eIF2α were analyzed by Western blot or real time PCR. The activity of JNK was also evaluated. Moreover, the insulin signaling proteins such as IRS-1 and AKT were determined by Western blot.

Results:

The production of glucose stimulated with insulin was reduced. The expressions of ORP150 was decreased both in gene and protein levels when cells were pretreated with berberine, while the activation of JNK was blocked. The levels of phosphorylation both on PERK and eIF2α were inhibited in cells pretreated with berberine. The level of IRS-1 ser³⁰⁷ phosphorylation was decreased, whereas IRS-1 tyr phosphorylation was increased notablely. AKT ser⁴⁷³ phosphorylation was also enhanced significantly in the presence of berberine.

Conclusion:

The antidiabetic effect of berberine in Hep G2 cells maybe related to attenuation of ER stress and improvement of insulin signal transduction.     

双(α-呋喃甲酸)氧钒对胰岛素抵抗3T3-L1脂肪细胞糖摄取的影响

目的探讨新型的有机羧酸氧钒配合物双(α-呋喃甲酸)氧钒(BFOV)对正常及胰岛素抵抗的3T3-L1脂肪细胞糖摄取的影响。方法采用地塞米松诱导3T3-L1脂肪细胞建立胰岛素抵抗的细胞模型,研究双(α-呋喃甲酸)氧钒对正常及胰岛素抵抗3T3-L1脂肪细胞葡萄糖消耗的影响。结果双(α-呋喃甲酸)氧钒(2.5μmol·L-1~40μmol·L-1)对正常的3T3-L1脂肪细胞仅有增加葡萄糖消耗量的趋势,与空白对照组比较,差异无显著性;但能明显增加地塞米松诱导的胰岛素抵抗3T3-L1脂肪细胞的葡萄糖消耗量,改善模型细胞的胰岛素抵抗状态。结论双(α-呋喃甲酸)氧钒能促进胰岛素抵抗脂肪细胞的葡萄糖摄取,改善胰岛素抵抗状态。