3T3-L1细胞分化过程中线粒体含量和葡萄糖摄取的动态变化

目的对分化过程3T3-L1细胞脂质含量、线粒体含量及细胞对葡萄糖的摄取进行动态观察,为选择适宜分化时点的脂肪细胞进行肥胖研究提供有力证据。方法经典鸡尾酒法诱导3T3-L1前脂肪细胞分化为成熟脂肪细胞。分别于分化的第0、2、4、6、8、10、12日,对细胞进行油红O染色,分光光度法检测细胞内脂质含量;Mito-Tracker Green探针法检测分化过程中线粒体含量变化;2-N[7-硝基苯-2-乙二酸,34羟氨基]-2-脱氧葡萄糖(2-NBDG)染色法直接观察细胞对葡萄糖摄取,葡萄糖氧化酶法测定培养基葡萄糖含量间接评价脂肪细胞对葡萄糖的摄取。结果 3T3-L1前脂肪细胞在分化第10日,镜下观察即有90%以上的细胞内可见大量脂滴呈"戒环样"分布。分化过程中3T3-L1细胞内脂质含量逐渐升高,线粒体含量逐渐增加,葡萄糖摄取逐步增强,至第10日趋于稳定。结论对于从成熟脂肪细胞的角度进行肥胖及其相关疾病的研究,选择分化第10日的3T3-L1脂肪细胞比较合理。     

TNF-α对3T3-L1成熟脂肪细胞中NYGGF4小鼠同源基因表达的影响

[目的]观察TNF-α对3T3-L1成熟脂肪细胞中NYGGF4小鼠同源基因表达水平以及胰岛素刺激下的葡萄糖摄取率的影响.[方法]体外培养3T3-L1前体脂肪细胞,诱导分化为成熟脂肪细胞后,应用不同浓度(10、25、50 ng/mL)重组TNF-α干预成熟脂肪细胞16 h,或以10 ng/mL重组TNF-α分别干预24、48、72 h,采用实时荧光定量RT-PCR技术检测TNF-α干预后3T3-L1脂肪细胞中NYGGF4小鼠同源基因mRNA表达水平;另外,采用[3H]-2-脱氧葡萄糖掺入法检测TNF-α干预24、48、72h后成熟脂肪细胞葡萄糖摄取率.[结果]1)不同浓度TNF-α均能显著上调3T3-L1成熟脂肪细胞中NYGGF4小鼠同源基因表达(P均<0.001),在0～25 ng/mL浓度范围内呈现浓度依赖性,随TNF-α干预浓度增高,NYGGF4小鼠同源基因的表达水平逐渐升高;2)TNF-α对3T3-L1成熟脂肪细胞中NYGGF4小鼠同源基因的表达调节具时间反应性,呈现随干预时间延长该基因表达逐渐上调的特征,10 ng/mL TNF-α干预人成熟脂肪细胞24 hNYGGF4小鼠同源基因mRNA表达水平即显著上调(P<0.001);3)TNF-α干预48 h,3T3-L1成熟脂肪细胞胰岛素刺激的葡萄糖摄取率与未干预组比较下降50%以上,干预72 h,胰岛素刺激的葡萄糖摄取受到进一步抑制.[结论]TNF-α可以上调3T3-L1成熟脂肪细胞中NYGGF4小鼠同源基因[目的]表达,抑制3T3-L1成熟脂肪细胞胰岛素刺激下的葡萄糖摄取.     

染料木黄酮对3T3-L1前脂肪细胞分化的作用及其机制研究

目的观察染料木黄酮(genistein,GEN)对3T3-L1前脂肪细胞分化的影响,探讨GEN抑制3T3-L1细胞分化的作用及分子机制。方法用含1-甲基-3-异丁基黄嘌呤、地塞米松和胰岛素的培养液(MDI)诱导3T3-L1前脂肪细胞分化,同时用GEN或p38抑制剂SB203580干预。作用6d后,用油红染色实验观察脂肪形成情况;检测细胞培养液中非酯化脂肪酸(NEFA)、甘油三酯(TG)的含量;用Western blotting技术检测细胞中脂肪酸合酶(FAS)的蛋白表达。用GEN预处理30min后,用胰岛素刺激3T3-L1细胞,检测磷酸化p38MAPK(p-p38)的蛋白表达。结果GEN可以有效抑制3T3-L1细胞的脂肪形成,降低培养液中NEFA、TG的含量。胰岛素刺激后,3T3-L1细胞中p-p38的表达迅速增强,并在5min时达到高峰,GEN可以有效降低p-p38的表达。GEN、SB203580均能降低FAS的蛋白表达。结论染料木黄酮能有效抑制3T3-L1前脂肪细胞的脂肪分化,其机制是通过p38途径对FAS的抑制发挥作用。     

不同时间持续缺氧对3 T3-L1脂肪细胞炎症因子mRNA的影响

目的探讨不同时间持续缺氧孵育后脂肪细胞肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)表达的变化。明确肥胖缺氧状态下是否存在炎症因子表达增加导致胰岛素抵抗(IR)。方法将3T3-L1脂肪细胞随机分为4组,即常氧和缺氧4 h、12 h、24 h组,实时定量PCR(q RT-PCR)法测定各时间点脂肪细胞缺氧诱导因子1-α(HIF-1α),葡萄糖转运子-1(GLUT-1),TNF-α,IL-6,IL-1β的mRNA。结果与常氧组相比,缺氧12 h、24 h组HIF-1α,GLUT-1 mRNA表达水平均升高,差异有统计学意义(P0.05)。结论缺氧使脂肪细胞HIF-1α,GLUT-1升高,确认脂肪细胞缺氧状态形成,在缺氧状态下炎症因子TNF-α,IL-6,IL-1β mRNA水平升高,缺氧处理24 h变化最为明显。     

明日叶查尔酮对胰岛素抵抗细胞PI3K-Akt-GLUT4信号通路的影响

目的研究明日叶查尔酮(Angelica keiskei chalcones,AC)对胰岛素抵抗L6细胞磷脂酰肌醇3激酶-蛋白激酶-葡萄糖转运体4(PI3K-Akt-GLUT4)信号通路的影响。方法采用高浓度胰岛素诱导的胰岛素抵抗L6细胞,分别加入5、10、20μmol/L终浓度的明日叶查尔酮共同培养24 h,葡萄糖氧化酶法测定细胞上清液中葡萄糖含量,逆转录聚合酶链式反应方法检测细胞PI3K和Akt的mRNA表达水平,蛋白印迹法检测GLUT4和Akt的蛋白表达水平。结果胰岛素抵抗组细胞培养液的葡萄糖含量显著高于空白对照组(P0.05),而PI3K mRNA、Akt mRNA和GLUT4、Akt蛋白表达水平则降低(P0.05);中、高剂量AC组细胞培养液葡萄糖含量均低于胰岛素抵抗组(P0.05),而PI3K mRNA、Akt mRNA和GLUT4、Akt蛋白表达水平则升高(P0.05)。结论明日叶查尔酮可上调L6细胞胰岛素抵抗模型PI3K-AktGLUT4信号通路的表达水平,增强其对葡萄糖的摄取利用,改善胰岛素抵抗。     

锌对胰岛素抵抗靶细胞活力和葡萄糖消耗量影响

目的探讨锌对胰岛素抵抗靶细胞活力和葡萄糖消耗量的影响。方法建成Hep G2细胞、3T3-L1细胞和L6成肌细胞胰岛素抵抗模型后,用10-7mol/L胰岛素和不同浓度锌(0、20、50、100、200、400μmol/L)孵育细胞,通过MTT法和葡萄糖氧化酶法测定基础状态和胰岛素刺激状态下3种胰岛素抵抗细胞葡萄糖的消耗量。结果不同剂量的锌孵育3种细胞3 h后,200、400μmol/L的锌可明显抑制各组细胞的活力(P<0.05);50~100μmol/L的锌干预3 h能在不同程度上提高Hep G2、3T3-L1正常细胞和胰岛素抵抗细胞的葡萄糖消耗量,但其作用效果明显低于胰岛素;其中100μmol/L的锌与胰岛素共同作用的效果分别优于胰岛素或锌单独作用的效果(P<0.05);对于L6肌细胞,20、50和100μmol/L锌均能明显提高基础状态下正常细胞和胰岛素抵抗细胞的葡萄糖消耗量(P<0.05);仅有20μmol/L锌和胰岛素共同作用的效果优于胰岛素或锌单独作用的效果(P<0.05)。结论不同浓度的锌可以在一定程度上提高3种胰岛素抵抗的靶细胞葡萄糖摄取量,且不同的细胞具有不同的适宜作用剂量。     

花色苷抗氧化及改善胰岛素抗性的体外研究

目的研究花色苷(Anth)体外抗氧化及改善胰岛素抗性(IR)的效应,并分析构效关系。方法以自然界最为常见的6种Anth作为受试物,测定其对二苯代苦味酰肼(1-diphenyl-2-picrylhydrazyl,DPPH?)自由基的清除能力,及其对H2O2诱导的IR3T3-L1脂肪细胞胞内活性氧(reactive oxygen species,ROS)水平和葡萄糖摄取能力的影响。结果6种Anth均具有较强的DPPH自由基清除能力,效应和B环上酚羟基数目有关;6种Anth中,具有邻苯二酚结构的2种能更好的清除H2O2诱导IR脂肪细胞胞内的ROS,同时显著提高胰岛素刺激后脂肪细胞对葡萄糖的摄取能力,呈剂量-效应依赖型。结论花色苷可预防和改善氧化应激引起的3T3-L1脂肪细胞胰岛素抗性,此效应与B环上的邻苯二酚结构有关。     

DHA和EPA调节3T3-L1脂肪细胞胰岛素抵抗及糖脂代谢的作用差异

目的 探讨n-3多不饱和脂肪酸DHA和EPA调节3T3-L1脂肪细胞胰岛素抵抗（insulin resistance,IR及糖脂代谢的剂量反应关系和作用差异。方法：用10ng/mlTNF-α处理分化成熟的3T3-L1脂肪细胞48h,诱导IR。使用Western blot检测胰岛素信号通路,葡萄糖氧化酶法(GOD-POD)法测定糖摄取,验证诱导IR效果。建模成功后,采用25、50、100、200、400μmol/L的DHA或EPA与TNF-α联合干预24h,同时设立对照组。干预后使用GOD-POD检测糖摄取量,油红O染色测定胞内甘油三酯（triglyceride,TG）,PCR测定固醇调节元件结合蛋白-1c(SREBP-1c)、乙酰辅酶A羧化酶（ACC）、脂肪酸合酶（FAS）、脂肪甘油三酯脂肪酶(ATGL)、激素敏感性脂肪酶(HSL)mRNA表达,Western blot检测胰岛素信号通路蛋白表达。结果：TNF-α损伤胰岛素信号通路,降低胰岛素敏感性,IR建模成功。在糖代谢方面,25～400μmol/L的DHA和EPA均能改善TNF-α损伤的糖摄取,其中100和200μmol/L的效果最...     

LRP16基因对胰岛素分泌和胰岛素抵抗的影响

本课题通过研究LRP16基因在MIN6（小鼠胰岛素瘤细胞）中的功能以及在3T3-L1（脂肪细胞）、C2-C12（肌肉细胞）、HepG2（肝细胞）中对胰岛素抵抗的影响发现，LRP16在MIN6中具有多种作用，如可通过调节胰岛素基因及其转录因子来调节胰岛素含量；     

胡柚果肉组分的降糖作用及其降糖成分分布研究

目的研究胡柚果肉不同极性组分单独和相互对3T3-L1脂肪细胞摄取葡萄糖的影响,并测定已知具有降血糖功效的成分在这些组分中的分布。方法将胡柚果肉乙醇提取物(EE)分成极性大小依次增加的石油醚、二氯甲烷、乙酸乙酯、正丁醇和水5个组分,测定其加入1 mg/L EE(EE1)前后3T3-L1脂肪细胞对葡萄糖的消耗量;并测定黄酮、类胡萝卜素、柠檬苦素、诺米林、橙皮苷和柚皮苷等成分在这些组分中含量。结果胡柚果肉中各组分均可促进3T3-L1脂肪细胞葡萄糖消耗;在加入EE1后,二氯甲烷组分和正丁醇组分与其联合作用效应与它们和EE1单独作用效应之和相比,促进3T3-L1脂肪细胞摄取葡萄糖的量基本相同,而石油醚组分(20 mg/L、30 mg/L)、乙酸乙酯组分(20 mg/L、30 mg/L)和水组分(20 mg/L、30 mg/L)与其联合作用效应与它们和EE1单独作用效应之和相比,显著抑制3T3-L1脂肪细胞摄取葡萄糖(P0.01);具有降血糖功效的黄酮类化合物主要分布在乙酸乙酯组分中,柚皮苷和橙皮苷含量较高,柠檬苦素类化合物主要存在于二氯甲烷组分中,含有柠檬苦素和诺米林,类胡萝卜素主要存在于石油醚组分中。结论胡柚果肉石油醚组分、乙酸乙酯组分和水组分中的某些物质会对3T3-L1脂肪细胞摄取葡萄糖发生拮抗作用。     

Scopoletin increases glucose uptake through activation of PI3K and AMPK signaling pathway and improves insulin sensitivity in 3T3-L1 cells

Coumarins have been shown to reduce blood glucose levels and improve insulin sensitivity in other studies. The purpose of this study was to investigate the effects of scopoletin, which is a type of coumarin family, on glucose uptake in 3T3-L1 cells to test the hypothesis that scopoletin exerts an antidiabetic function on adipocytes. Scopoletin significantly increased glucose uptake, which was associated with increased expression of the plasma membrane glucose transporter type 4 (PM-GLUT4) in 3T3-L1 adipocytes. This increase in PM-GLUT4 expression was promoted by phosphorylation of protein kinase B, activation of phosphatidylinositol-3-kinase (PI3K), and enhanced intracellular glucose uptake. Scopoletin also promoted phosphorylation of adenosine monophosphate–activated protein kinase (AMPK) and enhanced PM-GLUT4 expression. Scopoletin-induced glucose uptake in 3T3-L1 adipocytes was inhibited by treatment with the PI3K inhibitor wortmannin and the AMPK inhibitor compound C. These results suggest that scopoletin has an antidiabetic effect by stimulating GLUT4 translocation to the PM through activation of the PI3K and AMPK pathways in 3T3-L1 adipocytes, thereby upregulating glucose uptake.     

An extract of Lagerstroemia speciosa L. has insulin-like glucose uptake-stimulatory and adipocyte differentiation-inhibitory activities in 3T3-L1 cells

The effects of extracts isolated from Lagerstroemia speciosa L. (banaba) on glucose transport and adipocyte differentiation in 3T3-L1 cells were studied. Glucose uptake-inducing activity of banaba extract (BE) was investigated in differentiated adipocytes using a radioactive assay, and the ability of BE to induce differentiation in preadipocytes was examined by Northern and Western blot analyses. The hot water BE and the banaba methanol eluent (BME) stimulated glucose uptake in 3T3-L1 adipocytes with an induction time and a dose-dependent response similar to those of insulin. Furthermore, there were no additive or synergistic effects found between BE and insulin on glucose uptake, and the glucose uptake activity of insulin could be reduced to basal levels by adding increasing amounts of BE. Unlike insulin, BE did not induce adipocyte differentiation in the presence of 3-isobutyl-1-methylxanthine (IBMX) and dexamethasone (DEX). BE inhibited the adipocyte differentiation induced by insulin plus IBMX and DEX (IS-IBMX-DEX) of 3T3-L1 preadipocytes in a dose-dependent manner. The differences in the glucose uptake and differentiation inhibitory activities between untreated cells and those treated with BE were significant (P < 0.01). The inhibitory activity was further demonstrated by drastic reductions of peroxisome proliferator-activated receptor gamma2 (PPARgamma2) mRNA and glucose transporter-4 (GLUT4) protein in cells induced from preadipocytes with IS-IBMX-DEX in the presence of BE. The unique combination of a glucose uptake stimulatory activity, the absence of adipocyte differentiation activity and effective inhibition of adipocyte differentiation induced by IS-IBMX-DEX in 3T3-L1 cells suggest that BE may be useful for prevention and treatment of hyperglycemia and obesity in type II diabetics.     

Phospholipid Derivatives of Cinnamic Acid Restore Insulin Sensitivity in Insulin Resistance in 3T3-L1 Adipocytes

Background: Insulin resistance (IR) is a condition in which the physiological amount of insulin is insufficient to evoke a proper response of the cell, that is, glucose utilization. Metformin is the first choice for therapy, thanks to its glycemic efficacy and general tolerability. In addition, various natural compounds from plant extracts, spices, and essential oils have been shown to provide health benefits regarding insulin sensitivity. In the present study, we analyzed the effect of phospholipid derivatives of selected natural aromatic acids on insulin action and their potential use to overcome insulin resistance. Methods: The 3T3-L1 fibroblasts were differentiated into mature adipocytes; next, insulin resistance was induced by palmitic acid (16:0). Cells were further cultured with phenophospholipids at appropriate concentrations. To assess insulin sensitivity, we measured the insulin-stimulated glucose uptake, using a glucose uptake test. Results: We showed that cinnamic acid (CA) and 3-methoxycinnamic acid (3-OMe-CA) restored the proper insulin response. However, 1,2-dicinnamoyl-sn-glycero-3-phosphocholine (1,2-diCA-PC) and 1-cinnamoyl-2-palmitoyl-sn-glycero-3-phosphocholine (1-CA-2-PA-PC) improved insulin sensitivity in insulin-resistant adipocytes even stronger, exhibiting more beneficial effects. Conclusions: The binding of aromatic acids to phosphatidylcholine increases their beneficial effect on insulin sensitivity in adipocytes and expands their potential practical application as nutraceutical health-promoting agents.     

Soluble fibroin enhances insulin sensitivity and glucose metabolism in 3T3-L1 adipocytes

Type 2 diabetes is characterized by hyperglycemia and hyperinsulinemia, features of insulin resistance. In vivo treatment of ob/ob mice with hydrolyzed fibroin reverses these pathological attributes. To explore the mechanism underlying this effect, we used the murine, 3T3-L1 adipocyte cell line, which has been used extensively to model adipocyte function. Chronic exposure of 3T3-L1 adipocytes to insulin leads to a 50% loss of insulin-stimulated glucose uptake. Chronic exposure to different preparations of fibroin partially blocked the response to insulin but also increased the sensitivity of control cells to the acute action of insulin. The latter effect was most robust at physiologic concentrations of insulin. Fibroin did not prevent the insulin-induced downregulation of the insulin receptor or the tyrosine kinase activity associated with the receptor. Further, fibroin had no effect on the activity of the insulin-sensitive downstream kinase, Akt. Interestingly, fibroin accelerated glucose metabolism and glycogen turnover independent of insulin action. In addition, fibroin upregulated glucose transporter (GLUT)1, which increased its expression at the cell surface and enhanced GLUT4 translocation. Together, these phenomena may underlie the improvement in diabetic hyperglycemia noted in vivo in response to fibroin.     

Silk protein hydrolysate increases glucose uptake through up-regulation of GLUT 4 and reduces the expression of leptin in 3T3-L1 fibroblast

The purpose of our research was to test the hypothesis that silk protein hydrolysate increases glucose uptake in cultured murine embryonic fibroblasts. Insulin sensitizing activity was observed in a cell-based glucose uptake assay using 3T3-L1 embryonic fibroblasts. The treatment of 1 mg/mL of silk peptide E5K6 plus 0.2 nM insulin was associated with a significant increase in glucose uptake (124.0% ± 2.5%) compared to treatment with 0.2 nM insulin alone. When the 3T3-L1 cells were induced to differentiate into fibroblasts, fat droplets formed inside the cells. Silk peptide E5K6 reduced the formation of fat droplets at the 1-mg/mL dosage (86.1% ± 2.5%) when compared to the control (100.0% ± 5.8%). A 1 mg/mL dose of silk peptide E5K6 significantly increased GLUT 4 expression (131.5% ± 4.0%). The treatment of 1 mg/mL of silk peptide E5K6 did not present any changes for adipogenic expressed genes, but leptin expression was significantly increased by silk peptide E5K6 supplementation (175.9% ± 11.1%). From these results, silk peptide E5K6 increased glucose uptake via up-regulation of GLUT 4 and decreased fat accumulation via the up-regulation of leptin.     

Fructose alters adiponectin,haptoglobin and angiotensinogen gene expression in 3T3-L1 adipocytes

Fructose- or sucrose-rich diets can cause insulin resistance and increase the risk of cardiovascular disease. Adipokines are correlated with the development of these diseases in obesity. We hypothesize that fructose and sucrose induce insulin resistance via effects on adipokine gene expression in adipocytes. This study analyzed the effect of fructose or glucose on adiponectin, haptoglobin, and angiotensinogen gene expression in 3T3-L1 adipocytes. Ten days after differentiation, the cells were pretreated with serum- and glucose-free medium. Twenty-four hours later, fructose or glucose (0, 5, 10, or 20 mmol) was added into the medium, and the cells were collected after a further 24 hours. Adiponectin, haptoglobin, and angiotensinogen gene expression were determined. Adiponectin gene expression increased when 10 or 20 mmol glucose was added compared with that observed for the non–hexose-treated cells. A similar effect occurred when 5 mmol fructose was added. Glucose (10 mmol) and fructose (20 mmol) stimulated haptoglobin gene expression in 3T3-L1 adipocytes compared with 0 mmol, with glucose producing a more pronounced effect. Although 20 mmol fructose caused an increase in angiotensinogen gene expression, glucose did not. In conclusion, in this study of 2 hexoses revealed an increase in adiponectin gene expression, suggesting that the effect of a glucose-rich diet on the development of insulin resistance is not related to the effect of these hexoses on adipocyte adiponectin gene expression. However, insulin resistance and cardiovascular disease promoted by fructose-rich diets could be partially related to the effect of fructose on adiponectin and angiotensinogen gene expression.     

Protective effect of the hydroalcoholic extract from Lampaya medicinalis Phil. (Verbenaceae) on palmitic acid- impaired insulin signaling in 3T3-L1 adipocytes

BackgroundObesity is strongly associated with insulin resistance (IR). IR at the molecular level may be defined as a diminished activation of insulin signaling-related molecules (IRS-1/Akt/AS160) as well as reduced glucose uptake. Subject with obesity have elevated plasma levels of saturated fatty acids, such as palmitic acid (PA), which triggers insulin signaling disruption in vivo and in vitro. Infusions of Lampaya medicinalis Phil. (Verbenaceae) are used in folk medicine of Northern Chile to counteract inflammatory diseases. Hydroethanolic extracts of lampaya (HEL) contain considerable amounts of flavonoids that may explain the biological activity of the plant. The aim of this study was to assess whether HEL exposure protects against PA-disrupted insulin signaling and glucose uptake in adipocytes.MethodsCytotoxicity of a range of HEL concentrations (0.01–10 μg/mL) was evaluated in 3T3-L1 adipocytes. Cells were exposed or not to 0.1 μg/mL of HEL before adding 0.65 mM PA or vehicle and incubated with 100 nM insulin (or vehicle) for 15 min. Phosphorylation of Tyr-IRS-1, Ser-Akt, Thr-AS160 was evaluated by Western blot. Glucose uptake was assessed using the 2-NBDG analogue.ResultsHEL was not cytotoxic at any concentration assessed. PA-induced reduction in insulin-stimulated phosphorylation of IRS-1, Akt and AS160 and glucose uptake were abolished by co-treatment with HEL.ConclusionThese findings give new insights about the effect of HEL ameliorating PA- impaired IRS-1/Akt/AS160 pathway and glucose uptake in adipocytes. More studies should focus on lampaya, since might represent a preventive approach in individuals whose circulating PA levels contribute to IR.     

Cornus mas L. Increases Glucose Uptake and the Expression of PPARG in Insulin-Resistant Adipocytes

Cornus mas L., also known as cornelian cherry (CM), is a species that has long been cultivated in many different countries. In numerous scientific reports, cornelian cherry is used to treat numerous diseases and conditions. The presented study evaluated the effect of red and yellow Cornus mas L. extract on insulin sensitivity in adipocytes. 3T3-L1 fibroblasts as well as human SAT-derived and VAT-derived adipocytes were differentiated in vitro, and insulin resistance was induced using palmitic acid (16:0). The effect of CM fruit extract was analyzed in terms of glucose uptake and insulin signaling gene expression. In the glucose uptake test after insulin stimulation, a significant increase in glucose uptake was demonstrated in cells treated with CM fruit extracts. Furthermore, CM fruit extracts increased the expression of insulin signaling genes in adipocytes stimulated with insulin in control cells and adipocytes treated with CM extract. Additionally, a significant increase in peroxisome proliferator activated receptor gamma (PPARG) expression was observed in cells supplemented with CM extract. In conclusion, studies have shown that CM fruits can overcome insulin resistance and thus they have a positive effect on cell metabolism.     

Ethanol impairs insulin's actions through phosphatidylinositol 3-kinase

Insulin plays an important role in cell metabolism and proliferation. In the present study, we examined the effect of ethanol on insulin actions such as glucose uptake, DNA synthesis, and c-Jun gene expression. Acute treatment with ethanol (200 mM) for 60 minutes inhibited insulin-stimulated 2-deoxyglucose uptake by 50% in 3T3-L1 adipocytes. Insulin-induced DNA synthesis and c-Jun protein expression were also reduced by ethanol treatment in Rat-1 fibroblasts overexpressing normal human insulin receptor. Ethanol has no effect on tyrosine phosphorylation of the insulin receptor and insulin receptor substrate (IRS)-1. However, association of the insulin receptor and IRS-1 with the Src homology 2 domain of the p85 subunit of phosphatidylinositol 3-kinase (PI3-kinase) was reduced by ethanol. Pretreatment with the antidiabetic drug troglitazone, an insulin-sensitizer, reversed ethanol's inhibition. These results suggest that ethanol specifically inhibits the association of the insulin receptor and IRS-1 with the p85 subunit of PI3-kinase, which is required for increased glucose uptake, DNA synthesis, and c-Jun expression by insulin.