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1.
增龄对大鼠骨骼肌细胞葡萄糖转运蛋白的影响   总被引:6,自引:0,他引:6  
目的 探讨增龄对大鼠骨骼肌细胞葡萄糖转运蛋白4(glucose transporter 4,GLUT4)的影响。 方法 SD实验大鼠分为2组青年组(3月龄)和老年组(24月龄)各式各样0只。制务GLUT4羧基端正2肽的多克隆抗体,利用Western印迹法检测2组大鼠骨骼肌细胞GLUT4蛋白含量,并检测大鼠尾静脉血糖。 结果 老年组大鼠的血糖(5.6±0.5mmol/L)略高于青年组大鼠(4.5±0.5mmol/L),但差异无显著性;青年组大鼠骨骼肌细胞内GLUT4相对含量为109.62±12.25,而老年组为86.46±8.25,差异有显著性(P<0.05)。 结论 增龄可引起大鼠骨骼肌细胞GLUT4蛋白含量明显减少,使骨骼肌细胞对葡萄糖的转运发生障碍,这可能是老年人易产生胰岛素抵抗的机制之一。  相似文献   

2.
目的测定不同饮食喂养大鼠和替米沙坦、瑞舒伐他汀干预后大鼠产生胰岛素抵抗(IR)的情况,观察大鼠骨骼肌中小窝蛋白(Caveolin)1、葡萄糖转运蛋白(GLUT)4表达的变化。方法 4周龄Wistar雄性大鼠48只,以高糖高脂饮食诱导建立IR模型,以高糖高脂给药(替米沙坦、瑞舒伐他汀)诱导建立实验组,通过RT-PCR方法检测IR大鼠骨骼肌组织中Caveolin 1、GLUT4的表达水平。结果高糖高脂喂养组产生IR,给予替米沙坦、瑞舒伐他汀干预后IR明显改善,高糖高脂组Caveolin1 mRNA在骨骼肌中的表达明显高于对照组(P<0.05),高糖高脂组GLUT4 mR-NA在骨骼肌中的表达明显低于对照组(P<0.05),替米沙坦、瑞舒伐他汀可降低Caveolin1 mRNA在IR大鼠骨骼肌中的表达,升高GLUT4 mRNA在IR大鼠骨骼肌中的表达。结论①高糖高脂饲料喂养8 w可诱导大鼠IR。②IR大鼠骨骼肌组织Caveolin 1表达增加,GLUT4表达减少。③通过替米沙坦类、他汀类药物干预,可改善IR,降低Caveolin1表达水平,升高GLUT4表达水平。  相似文献   

3.
目的研究2型糖尿病(T2DM)sD大鼠血管紧张素Ⅱ受体拮抗剂(ARB)是否改善胰岛素抵抗及对IRSl磷酸化、P13K途径中Akt磷酸化及GLUT4转位的影响。方法42只sD大鼠分别给予高脂高糖饮食/链脲佐菌素(STZ)或普通饮食喂养,当空腹血糖(FPG)〉/7.8mmol/L且伴有胰岛素抵抗者为成模T2DM大鼠20只,正常组20只;分为正常不干预组(A组)、正常干预组(B组)、T2DM不干预组(C组)及T2DM干预组(D组),每组10只。B组及D组给予氯沙坦(4mg·k~·d“),干预6周后计算胰岛素敏感指数(ISI),取腓肠肌备用。通过免疫组织化学(IHC)及Westernbloting检测IRSl/P'yr_IRSl、Akt/Pser473-Akt及GLUT4蛋白表达。结果(1)成功制备了T2DM大鼠模型。IHC结果示C、D组较A、B组P”-IRSl、P-Akt蛋白表达减少;Westernbloting结果示Ptyr。-IRSl、GLUT4膜蛋白表达减少(P〈0.05)。(2)氯沙坦干预后,D组FBG(mmol/L)、FINS(p~U/M1)(18.8±4.1,27±5)较c组(19.74-3.7,27±6)降低,IsI升高(D组一6.18±0.08,C组一6.18±0.08,P〈0.05);IHC示Ptyr-IRSl蛋白表达升高(P〈0.05);Westernbloting示GLUT4膜蛋白、P-IRSl上升(P〈0.05),P-Akt蛋白的表达无差异(P〉0.05)。结论氯沙坦通过增加骨骼肌组织中GLUT4的转位而改善T2DM大鼠的胰岛素抵抗。  相似文献   

4.
目的研究高脂饮食喂养的胰岛素抵抗(IR)大鼠骨骼肌中蛋白激酶B(PKB)表达和葡萄糖转运蛋白4(GluT4)转位的改变及饮食治疗、葛根素、罗格列酮干预的影响。方法将雄性SD大鼠50只随机分为正常饮食(A)组和高脂饮食(B)组,2个月后再将B组大鼠随机分为高脂饮食(C)组、正常饮食干预(D)组、葛根素干预(E)组和罗格列酮干预(F)组。干预1个月后检测骨骼肌中PKB的表达及转位至质膜的GluT4含量。结果C组大鼠产生了明显的IR,骨骼肌中PKB的表达较A组显著降低(P<0.01),转位到质膜上的GluT4含量显著减低(P<0.01);D、E、F组大鼠IR明显改善,骨骼肌中PKB的表达较C组大鼠显著增加(P<0.01),GluT4含量较C组大鼠显著升高(P<0.01)。结论高脂饮食喂养的SD大鼠骨骼肌产生明显的IR,骨骼肌中Ins诱导的PKB表达降低,Ins刺激的GluT4向质膜的转位减少。饮食治疗及葛根素、罗格列酮干预能增加骨骼肌中Ins刺激的PKB表达及GluT4向质膜的转位。  相似文献   

5.
目的:研究姜黄素对STZ诱导糖尿病大鼠骨骼肌胰岛素抵抗的影响及其机制。方法:雄性SD大鼠腹腔注射STZ诱导糖尿病大鼠模型。成模大鼠分为糖尿病组(DM),糖尿病+姜黄素组(DM+Cur),糖尿病+缓冲液对照组(DM+NC)。以正常SD大鼠为正常对照组(NC)。DM+Cur组予姜黄素灌胃治疗,DM+NC组给予等体积缓冲液灌...  相似文献   

6.
[目的]探讨健脾理气化痰法针刺对高脂饲养胰岛素抵抗大鼠骨骼肌葡萄糖转运体4(GLuT4)蛋白表达及胰岛素敏感性的影响。[方法]40只Wistar大鼠分别用高脂饲料、普通饲料喂养。经高胰岛素-正常葡萄糖钳夹术确定高脂饲养制备IR模型成功后,将模型大鼠随机分为模型组和电针组(取足三里、中脘、丰隆、关元穴),普通饲料喂养组为正常组。治疗6周后,行腹腔糖耐量、腹腔胰岛素耐量实验测量各组大鼠血糖水平;治疗8周后,采用免疫组化法检测各组大鼠股四头肌GLUT4蛋白的表达。[结果]与模型组比较,电针组胰岛素降低血糖的效果显著增强(P〈o.01);与模型组比较,电针组股四头肌GLUT4蛋白的表达水平增加(P〈o.05)。[结论]健脾理气化痰法针刺具有提高胰岛素敏感性的作用,并能显著提高股四头肌GLUT4蛋白的表达水平。  相似文献   

7.
研究高脂饮食状态下Wistar大鼠骨骼肌中musclin基因表达及其与胰岛素抵抗以及糖尿病、葡萄糖转运蛋白4(GLUT-4)等的关系,结果 提示muselin的表达增加(1.39±0.36 vs 0.31±O.07,P<0.01)可能与胰岛素抵抗有关,有可能是胰岛素抵抗、糖尿病的一个前期信号,其作用可能与GLUT-4(1.27±O.32 vs 1.84±0.24.P相似文献   

8.
目的 探讨C-RP、APN在IR大鼠各组织的表达情况. 方法 19只SD大鼠,随机分为对照组(NC,n=9)与高脂组(HF,n=10),饲养20周后,行OGTT和胰岛素释放试验(IRT),采用实时荧光定量PCR(RT-PCR)及Northern blot法检测大鼠肝脏、脂肪组织C-RP及APN的表达. 结果 与NC组比较,HF组血糖、胰岛素水平增加,表明已处于IR状态.Northern blot检测显示,HF组脂肪组织中APN的表达较NC组下降(P<0.01).RT-PCR显示,HF组肝脏组织C-RP较NC组上升约62%(P<0.01),脂肪组织中C-RP的表达较NC组上升约88%(P<0.01). 结论 高脂饲养诱导的IR大鼠,肝脏、脂肪组织C-RP表达增加,而脂肪组织APN表达下降.  相似文献   

9.
目的 探讨线粒体融合蛋白2 (Mfn2)是否通过减轻氧化应激改善大鼠骨骼肌细胞IR.方法 建立高脂诱导骨骼肌细胞IR模型(PA组),以Mfn2基因重组腺病毒转染细胞(PMfn2组),观察细胞内葡萄糖摄取率、超氧化物歧化酶总活力(T-SOD)、过氧化氢酶(CAT)、活性氧簇(ROS)及MDA的改变. 结果 (1)与正常对照(NC)组相比,高脂(PA)组葡萄糖摄取率降低(P<0.01),T-SOD及CAT活性降低,ROS、MDA含量增加(P<0.05);(2)与PA组相比,Mfn2基因重组腺病毒转染(PMfn2)组T-SOD及CAT活力均增加(P<0.05);ROS水平、MDA含量降低(P<0.05);GSH-Px活力无明显改变. 结论 上调高脂干预后骨骼肌细胞的Mfn2水平可减轻细胞氧化应激,改善IR.  相似文献   

10.
目的 检测不同间歇低氧暴露时间对骨骼肌葡萄糖转运蛋白(GLUT)4与蛋白激酶B(PKB/Akt)2表达的影响,探讨二者在间歇低氧导致胰岛素抵抗中的作用.方法 选取健康雄性Sprague-Dawley大鼠40只,按照随机数字表法分为5组:常氧对照组(NC组),间歇低氧2周组(IH2组),间歇低氧4周组(IH4组),间歇低氧6周组(IH6组),间歇低氧8周组(IH8组),每组8只.IH2组、IH4组、IH6组、IH8组每天给予8h间歇低氧暴露(9:00~17:00),NC组室内环境正常饲养.检测各组空腹血糖和空腹胰岛素水平,计算稳态模型评估-胰岛素抵抗指数(HOMA-IR).采用免疫组织化学法检测大鼠骨骼肌GLUT4及Akt2蛋白的表达,蛋白表达量用平均灰度值表示,并分析GLUT4与Akt2的相关性.结果 与NC组相比,IH2组、IH4组、IH6组、IH8组空腹血糖、HOMA-IR升高,骨骼肌GLUT4与Akt2灰度值升高,并且随间歇低氧暴露时间的延长而升高明显(F =87.67~288.63,P均<0.05);与NC组相比,IH2组、IH4组、IH6组、IH8组空腹胰岛素升高,其中IH2组、IH4组、IH6组,随间歇低氧暴露时间的延长而升高明显,IH8组较IH6组下降(F=86.04,P<0.01).Pearson相关分析显示GLUT4与Akt2的表达呈正相关(r=0.895,P <0.05).结论 随着间歇低氧暴露时间的延长胰岛素抵抗程度增加,GLUT4与Akt2蛋白表达水平下降,二者在间歇低氧导致胰岛素抵抗的过程中起协同作用.  相似文献   

11.
不同种类游离脂肪酸对大鼠胰岛素抵抗的影响   总被引:5,自引:3,他引:5  
目的研究短期血浆游离脂肪酸(FFA)升高对大鼠肝脏和外周胰岛索作用的影响,比较不同饱和程度脂肪酸对大鼠肝脏和外周胰岛素抵抗的作用。方法分别给大鼠静脉输注脂肪乳(多不饱和脂肪酸) 肝素,油酸(OLE,单不饱和脂肪酸),猪油(LO,饱和脂肪酸) 肝素(LOH组)和生理盐水7 h,并在输注的最后2 h,行清醒状态高胰岛素-正血糖钳夹试验,测定血浆葡萄糖、FFA、胰岛素和C肽水平,观察不同脂肪酸对胰岛素介导的葡萄糖利用(GU)和肝葡萄糖生成(HGP)能力的影响。结果与生理盐水组比较,脂肪乳、OLE和.LOH组血浆FFA水平升高(均P<0.01)。在钳夹状态下,所有脂肪组的HGP高于生理盐水组(均P<0.01),而OLE组和LOH组的HGP明显高于脂肪乳组(均P<0.01),所有脂肪组GU下降(均P<0.01),但是不同脂肪组间GU差异无统计学意义。结论血浆脂肪酸短期升高能引起大鼠肝脏和外周胰岛素抵抗,多不饱和脂肪酸引起的肝胰岛素抵抗小于单不饱和脂肪酸或饱和脂肪酸,不同饱和程度脂肪酸诱导的周围胰岛素抵抗程度相似。  相似文献   

12.

Objective

It has been recently reported that atrial fibrillation (AF) is associated with inflammation and inflammatory cytokines, and n-3 polyunsaturated fatty acids (PUFAs) might be of anti-inflammatory effects. This study was to evaluate the anti-inflammatory effect of PUFAs on AF in a canine sterile pericarditis model.

Methods

20 dogs were randomly assigned to two groups: control group (10 dogs) and PUFA treatment group (10 dogs), in which sterile pericarditis was created by open-chest operation. PUFAs were administered orally (2 g/day) 4 weeks before the operation till the end of the study. Before and 2 days after the operation, CRP, IL-6, TNF-α levels, the inducibility and maintenance of AF, the atrial effective refractory period (AERPs), and intra-atrial conduction time were determined.

Results

Before the operation, there were no significant differences in any of the parameters between the two groups. On the second postoperative day, the PUFA group had a lower CRP level (7.6 ± 0.5 vs. 11.7 ± 1.3 mg/dl, P < 0.0001), a lower IL-6 level (112.0 ± 37.3 vs. 142.0 ± 19.6 pg/ml, P < 0.01), a lower TNF-α level (83.3 ± 8.5 vs. 112.4 ± 8.2 pg/ml, P < 0.0001), a less AF inducibility (percentage of burst attempts leading to AF episodes: 11 ± 7.4 vs. 28 ± 10.3, P < 0.001) and maintenance [median AF duration: 1105 s (655.8-1406.5) vs. 2516.5 s (1187-3361), P < 0.05], a longer AERP (133.4 ± 4.1 vs. 129.8 ± 4.3 ms, P < 0.05), and a shorter intra-atrial conduction time (46.6 ± 4.4 vs. 51.9 ± 4.8 ms, P < 0.05) than the control group.

Conclusions

Dietary n-3 PUFA supplementation attenuates the inducibility and maintenance of AF in the sterile pericarditis model by reducing the production of proinflammatory cytokines.  相似文献   

13.
Liver preconditioning (PC), defined as an enhanced tolerance to injuring stimuli induced by previous specific maneuvers triggering beneficial functional and molecular changes, is of crucial importance in human liver transplantation and major hepatic resection. For these reasons, numerous PC strategies have been evaluated in experimental models of ischemia-reperfusion liver injury, which have not been transferred to clinical application due to side effects, toxicity and difficulties in implementation, with the exception of the controversial ischemic PC. In recent years, our group has undertaken the assessment of alternate experimental liver PC protocols that might have application in the clinical setting. These include thyroid hormone (T3), n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA), or iron, which suppressed liver damage due to the 1 h ischemia-20 h reperfusion protocol. T3, n-3 LCPUFA and iron are hormetic agents that trigger biologically beneficial effects in the low-dose range, whose multifactorial mechanisms of action are discussed in the work.  相似文献   

14.
A high dietary intake of n-3 long chain polyunsaturated fatty acids (PUFA), eicosapentaenoic and docosahexaenoic acids, is associated with a reduced incidence of coronary events. Supplementation with pharmacological doses of the same may improve survival in patients with previous myocardial infarction and established heart failure. Such protective effects may be explained by the action of n-3 PUFA on systemic inflammation, hypertension, endothelial dysfunction, thrombosis, cardiac arrhythmias, heart rate variability and atherosclerotic plaque instability, which are involved in the pathogenesis of these clinical conditions. In this short paper we will review the evidence in support of these pleiotropic effects of n-3 fatty acids.  相似文献   

15.
目的:研究游离脂肪酸对3T3-L1脂肪细胞核因子NF-kBp65表达及转位的影响,探讨游离脂肪酸诱导胰岛素抵抗的分子机制.方法:诱导成熟的3T3-L1脂肪细胞与0.3,0.5,1.0 mmol/L的软脂酸(PA)培养6-24h,用葡萄糖氧化酶法检测培液中的葡萄糖消耗量,以2-脱氧-[~3H]-D-葡萄糖摄入法观察葡萄糖的转运率,用Western blot检测总NF-kBp65蛋白及核NF-kBp65蛋白的表达,用激光扫描共聚焦(CLSM)对NF-kBp65进行定位显示.0.3-1.0 mmol/L软脂酸作用6-24 h后,3T3-L1脂肪细胞的葡萄糖消耗明显减少(3.03±0.34,2.71±0.36,2.64±0.25 mmol/L),呈时间剂量依赖效应,其作用不需要胰岛素的存在;0.3-1.0 mmol/L软脂酸作用6-24 h显著减少3T3-L1脂肪细胞胰岛素刺激的葡萄糖转运率(64%,33%,32%),呈时间剂量依赖效应;核NF-kBp65蛋白表达明显增加,CLSM显示NF- kBp65核转位增加,但软脂酸对3T3-L1脂肪细胞总NF-kBp65蛋白的表达无明显影响.结论:游离脂肪酸可以诱导胰岛素抵抗,其分子机制可能与FFAs刺激NF-kB的活化转位调节相关基因的表达有关.  相似文献   

16.
AIMS/HYPOTHESIS: Epidemiological research indicates that long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) improve insulin resistance. The aim of this study was to investigate the effects of seafood consumption on insulin resistance in overweight participants during energy restriction. METHODS: In this 8 week dietary intervention, 324 participants (20-40 years, BMI 27.5-32.5 kg/m(2), from Iceland, Spain and Ireland) were randomised by computer to one of four energy-restricted diets (-30E%) of identical macronutrient composition but different LC n-3 PUFA content: control (n = 80; no seafood; single-blinded); lean fish (n = 80; 150 g cod, three times/week); fatty fish (n = 84; 150 g salmon, three times/week); (4) fish oil (n = 80; daily docosahexaenoic/eicosapentaenoic acid capsules, no other seafood; single-blinded). Fasting glucose, insulin, adiponectin, plasma triacylglycerol and fatty acids in erythrocyte membrane were measured at baseline and endpoint. Insulin resistance was calculated using the homeostasis model assessment of insulin resistance (HOMA-IR). Linear models with fixed effects and covariates were used to investigate the effects of seafood consumption on fasting insulin and HOMA-IR at endpoint in comparison with the control group. RESULTS: Of the participants, 278 (86%) completed the intervention. Fish oil intake was a significant predictor of fasting insulin and insulin resistance after 8 weeks, and this finding remained significant even after including weight loss, triacylglycerol reduction, increased LC n-3 PUFA in membranes or adiponectin changes as covariates in the statistical analysis. Weight loss was also a significant predictor of improvements. CONCLUSIONS/INTERPRETATION: LC n-3 PUFA consumption during energy reduction exerts positive effects on insulin resistance in young overweight individuals, independently from changes in body weight, triacylglycerol, erythrocyte membrane or adiponectin. Trial registration: ClinicalTrials.gov NCT00315770.  相似文献   

17.
Various types of polyunsaturated fatty acids (PUFAs) have been suggested to exert different effects on the colon in terms of promotion or inhibition of tumor development. Results of in vitro and in vivo studies are, however, inconsistent and it remains unclear whether or not the cellular effects of PUFAs change along with the malignant transformation of colonic cells. In this study, we used the NIH3T3 cell line and its SIC (sigmoid colon cancer) oncogene transformants to compare the effects of PUFAs on the proliferation of non-malignant and malignant cells. We also determined the cellular utilization of fatty acids in media by a high-performance liquid chromatography method. The addition of exogenous arachidonic acid (ARA, an n-6 fatty acid), eicosapentaenoic acid (EPA, n-3), and docosahexaenoic acid (DHA, n-3) exerted different effects on NIH3T3 cells, and on SIC transformants, in which selective inhibitory effects were observed at media concentrations ranging from 10 to 20 μg/ml. In cells cultured in media supplemented with EPA or DHA at a concentration of 2 μg/ml, which had no effect on cell proliferation, the cellular utilization of linoleic acid (n-6), a precursor of n-3 fatty acids, was inhibited. This inhibition was stronger in SIC transformants than in NIH3T3 cells (P < 0.05). There was no difference in the utilization of fatty acids between the two cell lines cultured in media supplemented with ARA. We conclude that the cellular response to exogenous long-chain PUFAs is modified during the course of malignant transformation, and that EPA and DHA (n-3 PUFAs) appear to have specific inhibitory effects on cancer cells and may thus enhance the host defense against colon cancer. (Received Dec. 10, 1996; accepted July 25, 1997)  相似文献   

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目的研究短期多不饱和脂肪酸增高对大鼠肝脏TG含量和胰岛素抵抗的影响。方法给大鼠输注脂肪乳,行清醒高胰岛素-正血糖钳夹试验,观察脂肪乳对葡萄糖利用和肝葡萄糖产生的影响。结果脂肪乳使血浆FFA和TG升高,使肝脏TG和肝葡萄糖产生亦明显升高,钳夹状态葡萄糖利用显著降低。结论短期多不饱和脂肪酸增高可引起肝脏TG蓄积和胰岛素抵抗。  相似文献   

20.
Abstract. Hagstrup Christensen J, Aarup Skou H, Madsen T, Tørring I, Berg Schmidt E (Aalborg Hospital, Aalborg; and Hjørring/Brønderslev Hospital, Hjørring, Denmark). Heart rate variability and n‐3 polyunsaturated fatty acids in patients with diabetes mellitus. J Intern Med 2001; 249: 545–552. Objectives. Dietary n‐3 polyunsaturated fatty acids (PUFA) derived from fish may reduce the incidence of sudden cardiac death (SCD). The aim of the present study was to examine associations between n‐3 PUFA and 24‐h heart rate variability in patients with type 1 and type 2 diabetes mellitus (DM). Design. Observational study. Setting. The out‐patient’s diabetic clinic at Hjørring Hospital, Hjørring, Denmark. Subjects. Forty‐three patients with type 1 DM and 38 patients with type 2 DM. Main outcome measures. The patients fulfilled a food‐questionnaire regarding fish consumption, whilst the content of n‐3 PUFA in platelets was measured and 24‐h heart rate variability (HRV) was obtained. Results. The patients fish consumption was strongly related to their content of n‐3 PUFA in platelets. Furthermore, in patients with type 1 DM a close positive association was found between the content of n‐3 PUFA in platelets and 24‐h HRV. This association was not significant in patients with type 2 DM. Conclusions. The positive association between n‐3 PUFA in platelets and HRV may indicate a beneficial effect of n‐3 PUFA on HRV in patients with type 1 DM. Further studies are warranted to clarify whether supplementation with n‐3 PUFA reduce the risk of SCD amongst patients with DM.  相似文献   

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