补肾通脉方对Ⅱ型糖尿病大鼠骨骼肌胰岛素受体表达的影响

目的：探讨补肾通脉方对Ⅱ型糖尿病大鼠骨骼肌胰岛素受体表达的影响。方法：采用小剂量链脲佐菌素加高热量饲养方法建立Wistar大鼠Ⅱ型糖尿病模型，并随机分为模型组、中药组及西药组(分别用补肾通脉方和二甲双胍干预8周)，另设正常组(喂以普通饲料)；检测骨骼肌组织中三酰甘油(mTG)含量；以逆转录聚合酶链式反应(RT-PCR)检测骨骼肌组织胰岛素受体(InsR)mRNA的表达水平。结果：与正常组相比，模型组骨骼肌组织mTG水平明显升高(P＜0.01)，而InsR mRNA表达显著减少(P＜0．01)；与模型组比较，中药组骨骼肌组织mTG水平显著降低(P＜0．01)，InsR mRNA表达则显著增提高(P＜0.01)。结论：补肾通脉方改善胰岛素抵抗的作用机制可能与其上调Ⅱ型糖尿病大鼠骨骼肌组织InsR mRNA表达水平有关。     

小牛血清去蛋白注射液对2型糖尿病胰岛素抵抗大鼠模型骨骼肌GLUT4 mRNA表达的影响

目的观察小牛血清去蛋白注射液(DECB)对2型糖尿病胰岛素抵抗模型大鼠骨骼肌中葡萄糖转运因子4(GLUT4)的mRNA表达的影响。方法以高脂高糖饮食加链脲佐菌素制作2型糖尿病胰岛素抵抗大鼠模型,观察DECB对大鼠葡萄糖耐量(OGTT),运用RT-PCR方法检测大鼠模型骨骼肌中GLUT-4的mRNA表达。结果 DECB可改善OGTT,增加大鼠模型骨骼肌中GLUT4的mRNA表达。结论 DECB具有较好的降血糖、改善胰岛素抵抗、防治糖尿病并发症的作用。     

金芪降糖片对胰岛素抵抗和高血压的影响

目的：观察中药金芪降糖片对果糖诱导的胰岛素抵抗高血压大鼠胰岛素敏感性和血压的影响。方法：Wistar大鼠40只，30只建立果糖诱导的胰岛素抵抗高血压大鼠模型，设对照组(C组)10只以普通水灌胃。果糖饮水加罗格列酮治疗组(R组)10只，以罗格列酮溶液灌胃；果糖饮水加金苠降糖片治疗组(J组)10只，以金芪降糖片溶液灌胃；果糖饮水加果糖灌胃组(F组)10只，以10％果糖的普通水灌胃，共灌胃6周，实验前后测定大鼠尾动脉压，结束后取血测定血清空腹血糖(FBG)、空腹血清胰岛素浓度(n=NS)、血清抵抗素浓度(resistin)。计算胰岛素敏感性指数(ISI)。结果：实验结束后J组、R组和C组ISI均明显高于F组，同时血压明显低于F组；抵抗素水平J组、R组明显低于F组。结论：中药金芪降糖片可改善胰岛素抵抗个体胰岛素敏感性，并降低血压。     

葡萄糖和胰岛素调节三明治肝细胞中胆酸相关转运体表达及功能

目的:测定葡萄糖、胰岛素等糖尿病血糖中的异常因素对体外培养肝细胞中胆汁酸相关转运体表达及功能的影响.方法:分离并用三明治法培养大鼠原代肝细胞,用不同浓度葡萄糖或胰岛素培养72 h,使用胆盐类似物Cholyl-lysyl-fluorescein(CLF)进行摄取转运体钠/胆汁酸共转运体(Na+/bile acid cotransporter,ntcp)及外排转运体胆盐外排泵(Bile salt export pump,bsep)转运体功能学实验,并用荧光定量PCR法测定胆汁酸相关转运体ntcp、bsep及调节胆汁酸代谢转运的核受体(Farnesoid X receptor,fxr)的mRNA表达变化.结果:高浓度的葡萄糖和胰岛素均使CLF的胆泡排泄减少.高糖和高胰岛素均能够降低ntcp的表达)3～4倍),增加bsep的表达(约2倍),高糖能够降低fxr的水平(约0.5倍),高胰岛素增加fxr的水平(约1.5倍).结论:葡萄糖和胰岛素水平异常均会对胆汁酸相关转运体表达和功能造成影响;三明治原代肝细胞可用于胆酸和药物肝胆分布研究.     

NIDDM大鼠骨骼肌组织GLUT4mRNA表达及其与胰岛素分泌关系的实验研究

目的 观察非胰岛素依赖型糖尿病（NIDDM）大鼠骨骼肌葡萄糖转运体4（glucose transporter4,GLUT4)mRNA表达及其与胰岛素分泌的关系。方法 制备NIDDM大鼠模型,用Northern blot方法测定骨骼肌组织中GLUT4mRNA表达量;放射免疫法测定血清胰岛素含量;免疫组化法观察胰岛素阳性β细胞。结果 NIDDM大鼠骨骼肌GLUT4mRNA表达显低下,仅为对照组的45％（P＜0.01);其空腹基础胰岛素水平正常,但葡萄糖耐量试验胰岛素水平较对照组明显降低,2h胰岛素分泌有延迟现象;免疫组化实验NIDDM大鼠胰岛体积减少一半以上,胰岛素阳性β细胞数量明显减少。结论 NIDDM大鼠骨骼肌GLUT4mRNA表达量低下,该反应与体内胰岛素分泌水平呈现一定的正相关性。     

Far-infrared rays enhance mitochondrial biogenesis and GLUT3 expression under low glucose conditions in rat skeletal muscle cells

Far-infrared rays (FIR) are known to have various effects on atoms and molecular structures within cells owing to their radiation and vibration frequencies. The present study examined the effects of FIR on gene expression related to glucose transport through microarray analysis in rat skeletal muscle cells, as well as on mitochondrial biogenesis, at high and low glucose conditions. FIR were emitted from a bio-active material coated fabric (BMCF). L6 cells were treated with 30% BMCF for 24 h in medium containing 25 or 5.5 mM glucose, and changes in the expression of glucose transporter genes were determined. The expression of GLUT3 (Slc2a3) increased 2.0-fold (p < 0.05) under 5.5 mM glucose and 30% BMCF. In addition, mitochondrial oxygen consumption and membrane potential (ΔΨ_m) increased 1.5- and 3.4-fold (p < 0.05 and p < 0.001), respectively, but no significant change in expression of Pgc-1a, a regulator of mitochondrial biogenesis, was observed in 24 h. To analyze the relationship between GLUT3 expression and mitochondrial biogenesis under FIR, GLUT3 was down-modulated by siRNA for 72 h. As a result, the ΔΨ_m of the GLUT3 siRNA-treated cells increased 3.0-fold (p < 0.001), whereas that of the control group increased 4.6-fold (p < 0.001). Moreover, Pgc-1a expression increased upon 30% BMCF treatment for 72 h; an effect that was more pronounced in the presence of GLUT3. These results suggest that FIR may hold therapeutic potential for improving glucose metabolism and mitochondrial function in metabolic diseases associated with insufficient glucose supply, such as type 2 diabetes.     

Glucose metabolism and insulin receptor signal transduction in Alzheimer disease

Nosologically, Alzheimer disease is not a single disorder in spite of a common clinical phenotype. Etiologically, two different types or even more exist. (1) In a minority of about 5% or less of all cases, Alzheimer disease is due to mutations of three genes, resulting in the permanent generation of βA4. (2) The great majority (95% or more) of cases of Alzheimer disease are sporadic in origin, with old age as main risk factor, supporting the view that susceptibility genes and aging contribute to age-related sporadic Alzheimer disease. However, disturbances in the neuronal insulin signal transduction pathway may be of central pathophysiological significance. In early-onset familial Alzheimer disease, the inhibition of neuronal insulin receptor function may be due to competitive binding of amyloid beta (Aβ) to the insulin receptor. In late-onset sporadic Alzheimer disease, the neuronal insulin receptor may be desensitized by inhibition of receptor function at different sites by noradrenaline and/or cortisol, the levels of which both increase with increasing age. The consequences of the inhibition of neuronal insulin signal transduction may be largely identical to those of disturbances of oxidative energy metabolism and related metabolism, and of hyperphosphorylation of tau-protein. As far as the metabolism of amyloid precursor protein (APP) in late-onset sporadic Alzheimer disease is concerned, neuronal insulin receptor dysfunction may result in the intracellular accumulation of Aβ and in subsequent cellular damage. In this context, the desensitization of the neuronal insulin receptor in late-onset sporadic Alzheimer disease is different from that occurring in normal aging and early-onset familial Alzheimer disease. In late-onset sporadic Alzheimer disease changes in the brain are similar to those caused by non-insulin-dependent diabetes mellitus.     

六黄合剂对胰岛素抵抗大鼠糖耐量和血清胰岛素的影响

目的探讨六黄合剂对胰岛素抵抗大鼠糖耐量和血清胰岛素的影响。方法应用地塞米松致大鼠胰岛素抵抗(IR)模型,观察六黄合剂对大鼠血糖、血清胰岛素的变化。结果六黄合剂能够降低胰岛素抵抗大鼠口服葡萄糖耐量试验后2h血糖浓度(2hBG)和空腹血清胰岛素水平(FINS)(P<0.01)。结论六黄合剂可以改善葡萄糖耐量减退(IGT)和IR。     

二甲双胍与罗格列酮对2型糖尿病大鼠GLUT4表达的比较

目的比较二甲双胍与罗格列酮对2型糖尿病大鼠骨骼肌葡萄糖转运蛋白4(GLUT4)mRNA表达的影响.方法以低剂量链脲佐菌素(STZ)加高热量饲料喂养制作模型,灌胃给药4周,检测糖耐量、空腹血清胰岛素(Ins)及骨骼肌GLUT4 mRNA表达量的变化.结果造模后大鼠注射葡葡糖后30,60,120min血糖显著升高,空腹Ins无明显变化,骨骼肌GLUT4 mRNA表达量显著降低.两药均可使注糖后120min血糖下降;罗格列酮尚可降低空腹血糖.二甲双胍可使骨骼肌GLUT4 mRNA表达量明显升高,但罗格列酮对骨骼肌GLUT4 mRNA表达的降低无影响.结论本造模方法可导致大鼠产生类似2型糖尿病的变化,两药均可改善此模型糖耐量异常,二甲双胍的作用与增强骨骼肌GLUT4基因表达有关,而罗格列酮的作用可能与其它环节有关.     

羁糖脂对HepG2胰岛素抵抗细胞葡萄糖代谢及相关蛋白表达的影响

目的 通过体外实验探讨羁糖脂改善2型糖尿病胰岛素抵抗（IR）的作用,并初步探明其作用机制。方法 采用1×10^-7 mol/L胰岛素诱导HepG2细胞,建立IR细胞模型;MTT法检测羁糖脂对HepG2细胞的增殖抑制率;葡萄糖氧化酶-过氧化物酶（GOD-POD）法检测羁糖脂对HepG2 IR细胞葡萄糖吸收的影响;Western blotting法检测胰岛素受体底物1磷酸化丝氨酸p-IRS-1（Ser307）、磷酸酰肌醇-3-激酶（PI3K）、葡萄糖转运体-4（GLUT-4）的表达。结果 HepG2细胞置于含10^-7胰岛素培养液孵育24 h,与对照组比较,葡萄糖吸收水平下降,表明建模成功;30～120 μg/mL羁糖脂均能显著增加IR细胞葡萄糖吸收率,显著上调GLUT-4、PI3K蛋白表达水平,显著下调IRS-1 Ser307磷酸化水平。结论 羁糖脂能有效增强HepG2 IR细胞对葡萄糖的消耗能力,推测与上调GLUT-4、PI3K蛋白表达,抑制IRS-1丝氨酸磷酸化相关。     

胰岛素与硒对链脲佐菌素诱导的糖尿病大鼠心肌胰岛素信号转导的联合作用

为阐明小剂量胰岛素(1u.kg-1)与硒(180μg.kg-1)对糖尿病大鼠糖脂代谢及其对心肌细胞胰岛素信号分子表达的联合作用,采用One TouchⅡ血糖仪和血糖试纸测定血糖水平;微柱法测定糖化血红蛋白浓度;酶学法测定甘油三酯(TG)和总胆固醇(TC)含量;免疫印迹和免疫组化法检测心肌细胞中PI3K和GLUT4表达的变化。结果表明,联合用药组血糖和血脂明显下降(P<0.01);同时联合用药明显增加糖尿病大鼠心肌细胞上PI3K和GLUT4的表达(P<0.01)。整体动物实验结果表明:胰岛素和硒联合应用在降低血糖和血脂方面发挥了协同作用;胰岛素与硒联合应用通过改善糖尿病大鼠心肌细胞胰岛素信号转导通路中PI3K的表达,从而改善了GLUT4的移位障碍,最终改善心肌的能量代谢。     

胰升糖素样肽-1对胰岛β细胞胰岛素基因表达的调节作用

目的 研究不同浓度胰升糖素样肽-1（GLP-1）对大鼠胰岛β细胞胰岛素基因表达的影响,探讨GLP-1在2型糖尿病治疗中的作用。方法 不同刺激浓度的GLP-1（0nmol／L、1nmol／L、10nmol／L、10^2nmol／L、10^3nmol／L）与葡萄糖浓度分别为2．2mmol／L、5．5mmol／L、11.1mmol／L的RPMI1640营养液共培养24h后,提取细胞总RNA,运用半定量RT-PCR技术检测胰岛素基因表达的变化。结果 葡萄糖浓度为2．2mmol／L和5．5mmol／L时,随GLP-1浓度升高,胰岛素基因表达量呈钟型方式升高;葡萄糖浓度为11．1mmol／L时,随GLP-1浓度升高,胰岛素基因表达量呈浓度依赖性升高。结论 GLP-1以葡萄糖依赖和浓度依赖方式促进胰岛素基因的表达。     

脂联素影响骨骼肌胰岛素抵抗模型中葡萄糖转运蛋白4表达的研究

目的：通过建立骨骼肌L6细胞胰岛素抵抗模型,探讨骨骼肌L6细胞中脂联素（ APN）的分泌,以及脂联素对骨骼肌胰岛素抵抗模型中葡萄糖转运蛋白4（GLUT4）表达的影响。方法（1）体外培养大鼠L6成肌细胞,诱导分化后,给予不同浓度的棕榈酸（PA）,测定不同时间细胞培养上清液葡萄糖浓度,观察PA对L6细胞摄取葡萄糖的影响,建立胰岛素抵抗模型;（2）根据实验条件的不同分为三组：NC组（正常对照组,即骨骼肌L6细胞组）;IR组（胰岛素抵抗模型组）;IR＋PIO组（胰岛素抵抗模型＋吡格列酮组）。应用Western blot方法分别测定上述三组APN和GLUT4表达水平。结果（1）0．4 mmol· L^-1的棕榈酸在作用12、24、36 h以及0．6～0．8 mmol· L^-1棕榈酸作用8～36 h后,细胞培养上清液中葡萄糖含量,明显高于对照组。胰岛素抵抗模型建立;（2）Western blot结果显示：①与NC组比较,IR组APN和GLUT4表达均减少,差异有统计学意义;②与IR组比较,IR＋PIO组其APN和GLUT4表达均增加,差异有统计学意义。结论（1）大鼠L6成肌细胞培养并诱导分化后,经过一定条件下PA刺激,可以建立胰岛素抵抗模型;（2）大鼠L6细胞可分泌和表达脂联素,骨骼肌源性脂联素上调L6细胞GLUT4的表达;（3）吡格列酮作为PPAR-γ激动剂,可增加大鼠L6细胞脂联素的分泌,进而改善胰岛素敏感性。