低氧暴露与运动对肌糖原合成的调节机理研究
摘要
目的:探讨低氧暴露与运动对肌糖原合成的调节机理,以胰岛素调节肌糖原合成的信号途径作为研究主线,并对低氧暴露与运动调节葡萄糖转运的另一个重要信号途径AMPK进行研究。同时对影响肌糖原合成的下游信号—葡萄糖转运载体4(GLUT4)和糖原生成素(GN)进行研究。
方法:以SD雄性大鼠为研究对象,将其分为安静对照组、低氧暴露组、常氧运动组和高住低训组,运动方式为跑台运动,坡度为5度,跑速为20米/分,每周6天,共4周。晚上在氧浓度13.6%的低氧帐篷内低氧暴露12小时,共4周。分别于实验1天、7天、28天和复氧7天取材。观察胰岛β细胞形态与分泌功能、测定骨骼肌胰岛素受体亲和力、探讨调节肌糖原合成的信号通路PI-3K、AMPK、GLUT4和GN蛋白或基因表达在低氧与运动中的变化。
结果:(1)间歇性低氧暴露和高住低训在初期,胰腺腺泡在形态上有明显到中度脂肪变性,但随着低氧暴露时间的延长,腺泡脂肪变性减轻。(2)图像分析表明,运动可使胰岛β细胞数量增加,β细胞/胰岛面积百分比增加,而低氧暴露和高住低训则使之减少。(3)从I/G与C/G比值可见,常氧运动和高住低训无显著性差异。(4)低氧和/或运动对胰岛素低亲和力受体的影响更加显著,体现在胰岛素受体亲和力下降,但胰岛素受体结合容量非常显著性增加。(5)常氧运动和高住低训增加骨骼肌肌糖原的含量,且常氧运动更为显著。(6)低氧和/或运动能够增加骨骼肌AMPK和PI3K蛋白的含量,且7天组AMPK和28天组PI3K蛋白含量的增加更为显著。(7)低氧和/或运动能够增加GLUT4mRNA和GNmRNA的表达,且28天组二者增加更为显著。
结论:(1)低氧导致胰腺腺泡脂肪变性,但低氧和/或运动均未明显改变胰岛β细胞的正常分泌功能。(2)低氧和/或运动诱导或增强了胰岛素低亲和力受体的密度,说明胰岛素对低氧和/或运动的反应能力增强。(3)低氧和/或运动能够增加骨骼肌肌糖原的含量,但常氧运动更有利于肌糖原的合成。其机理是:一方面通过改变骨骼肌胰岛素受体亲和力及其结合容量、增加骨骼肌PI3K蛋白含量,增强了胰岛素信号途径的作用;另一方面也通过增加AMPK蛋白含量来促进葡萄糖转运。同时低氧和/或运动能够增加GLUT4mRNA和GNmRNA的表达,这对于低氧和/或运动促进骨骼肌肌糖原合成起着重要的作用。
Purpose:The purpose of this study was to explore the regulating mechanism of hypoxia exposure and exercise on muscle glycogen synthesis.The main study was the signaling pathway of insulin regulating muscle glycogen synthesis,and we researched on AMPK which was also an important signaling way of regulating glucose transport.Meanwhile, their downstream signals-GLUT4 and GN were studied.
Methods:As the subjects of this study,male Sprague-Dawley rats were divided into four groups:Control group,Hypoxia exposure group,Exerxise group and Living high training low(HiLo) group.The mode of exercise was to run on the treadmill,The grade of which was 5,and the speed was 20m/min, lasting for 6 days every week.At night,Hypoxia exposure and HiLo group were exposured in normobaric hypoxic tent where the concentration of oxygen was 13.6%for 12 hours.All these had been lasting 4 weeks,then the rats of each group were killed after the experiment lasting lday, 7days,28days and 35days(7days after restored normal oxygen),and the sample were collected.We observed and analysed the shape and function of pancreas beta cells,measured the affinity of insulin receptors and explored the mRNA and protein expression changes of PI3K,AMPK,GLUT4 and GN which regulated muscle glycogen synthesis in the hypoxia exposure and exercise.
Results:(1) The pancreas cells of Hypoxia exposure and HiLo,were obviously and moderately degenerated with adipic shape at lday and 7days after experiment.As the experiment were prolonged,the degeneration were to be lessen.(2) The results of image analysis indicated:exercise increased the numbers of pancreas beta cells,the percentage of beta cells and the area of pancreas were also increased.But all these of Hypoxia exposure and HiLo group were decreased.(3) As the ratio of I/G and C/G, we observed that there was no difference between exercise and HiLo.(4) The effects of hypoxia and/or exercise on insulin receptor of low affinity were more noticeable,hypoxia and/or exercise decreased the affinity of insulin receptor,but obviously increased the number of insulin receptor. (5) Hypoxia and/or exercise increased the content of muscle glycogen, and exercise increased more obviously.(6) Hypoxia and/or exercise increased the protein of AMPK and PI3k,and the protein of AMPK of 7days group and the protein of PI3k of 28 days group increased more obviously. (7) Hypoxia and/or exercise increased the gene expression of GLUT4 and GN,and which of the 28 days groups,were increased more obviously.
Conclusions:(1) Hypoxia made the pancreas cells degenerated with adipic shape,,but hypoxia and /or exercise did not obviously change the endocrine fuction of pancreas beta cells.(2) Hypoxia and /or exercise induced or increased the numbers of insulin receptor,which indicated that the responses of insulin to hypoxia and /or exercise were enhanced. (3) Hypoxia and/or exercise increased the content of muscle glycogen,and exercise increased more obviously.The mechanism of which included two signaling way:one was through changing the affinity and the numbers of insulin receptor,increasing the protein of PI3K,and then enhancing the action of insulin signaling pathway;the other was through increasing the protein of AMPK which promoted glucose transport.Moreover hypoxia and/or exercise also increased the gene expression of GLUT4 and GN,which played important roles on promoting muscle glycogen synthesis of hypoxia and/or exercise.
方法:以SD雄性大鼠为研究对象,将其分为安静对照组、低氧暴露组、常氧运动组和高住低训组,运动方式为跑台运动,坡度为5度,跑速为20米/分,每周6天,共4周。晚上在氧浓度13.6%的低氧帐篷内低氧暴露12小时,共4周。分别于实验1天、7天、28天和复氧7天取材。观察胰岛β细胞形态与分泌功能、测定骨骼肌胰岛素受体亲和力、探讨调节肌糖原合成的信号通路PI-3K、AMPK、GLUT4和GN蛋白或基因表达在低氧与运动中的变化。
结果:(1)间歇性低氧暴露和高住低训在初期,胰腺腺泡在形态上有明显到中度脂肪变性,但随着低氧暴露时间的延长,腺泡脂肪变性减轻。(2)图像分析表明,运动可使胰岛β细胞数量增加,β细胞/胰岛面积百分比增加,而低氧暴露和高住低训则使之减少。(3)从I/G与C/G比值可见,常氧运动和高住低训无显著性差异。(4)低氧和/或运动对胰岛素低亲和力受体的影响更加显著,体现在胰岛素受体亲和力下降,但胰岛素受体结合容量非常显著性增加。(5)常氧运动和高住低训增加骨骼肌肌糖原的含量,且常氧运动更为显著。(6)低氧和/或运动能够增加骨骼肌AMPK和PI3K蛋白的含量,且7天组AMPK和28天组PI3K蛋白含量的增加更为显著。(7)低氧和/或运动能够增加GLUT4mRNA和GNmRNA的表达,且28天组二者增加更为显著。
结论:(1)低氧导致胰腺腺泡脂肪变性,但低氧和/或运动均未明显改变胰岛β细胞的正常分泌功能。(2)低氧和/或运动诱导或增强了胰岛素低亲和力受体的密度,说明胰岛素对低氧和/或运动的反应能力增强。(3)低氧和/或运动能够增加骨骼肌肌糖原的含量,但常氧运动更有利于肌糖原的合成。其机理是:一方面通过改变骨骼肌胰岛素受体亲和力及其结合容量、增加骨骼肌PI3K蛋白含量,增强了胰岛素信号途径的作用;另一方面也通过增加AMPK蛋白含量来促进葡萄糖转运。同时低氧和/或运动能够增加GLUT4mRNA和GNmRNA的表达,这对于低氧和/或运动促进骨骼肌肌糖原合成起着重要的作用。
Purpose:The purpose of this study was to explore the regulating mechanism of hypoxia exposure and exercise on muscle glycogen synthesis.The main study was the signaling pathway of insulin regulating muscle glycogen synthesis,and we researched on AMPK which was also an important signaling way of regulating glucose transport.Meanwhile, their downstream signals-GLUT4 and GN were studied.
Methods:As the subjects of this study,male Sprague-Dawley rats were divided into four groups:Control group,Hypoxia exposure group,Exerxise group and Living high training low(HiLo) group.The mode of exercise was to run on the treadmill,The grade of which was 5,and the speed was 20m/min, lasting for 6 days every week.At night,Hypoxia exposure and HiLo group were exposured in normobaric hypoxic tent where the concentration of oxygen was 13.6%for 12 hours.All these had been lasting 4 weeks,then the rats of each group were killed after the experiment lasting lday, 7days,28days and 35days(7days after restored normal oxygen),and the sample were collected.We observed and analysed the shape and function of pancreas beta cells,measured the affinity of insulin receptors and explored the mRNA and protein expression changes of PI3K,AMPK,GLUT4 and GN which regulated muscle glycogen synthesis in the hypoxia exposure and exercise.
Results:(1) The pancreas cells of Hypoxia exposure and HiLo,were obviously and moderately degenerated with adipic shape at lday and 7days after experiment.As the experiment were prolonged,the degeneration were to be lessen.(2) The results of image analysis indicated:exercise increased the numbers of pancreas beta cells,the percentage of beta cells and the area of pancreas were also increased.But all these of Hypoxia exposure and HiLo group were decreased.(3) As the ratio of I/G and C/G, we observed that there was no difference between exercise and HiLo.(4) The effects of hypoxia and/or exercise on insulin receptor of low affinity were more noticeable,hypoxia and/or exercise decreased the affinity of insulin receptor,but obviously increased the number of insulin receptor. (5) Hypoxia and/or exercise increased the content of muscle glycogen, and exercise increased more obviously.(6) Hypoxia and/or exercise increased the protein of AMPK and PI3k,and the protein of AMPK of 7days group and the protein of PI3k of 28 days group increased more obviously. (7) Hypoxia and/or exercise increased the gene expression of GLUT4 and GN,and which of the 28 days groups,were increased more obviously.
Conclusions:(1) Hypoxia made the pancreas cells degenerated with adipic shape,,but hypoxia and /or exercise did not obviously change the endocrine fuction of pancreas beta cells.(2) Hypoxia and /or exercise induced or increased the numbers of insulin receptor,which indicated that the responses of insulin to hypoxia and /or exercise were enhanced. (3) Hypoxia and/or exercise increased the content of muscle glycogen,and exercise increased more obviously.The mechanism of which included two signaling way:one was through changing the affinity and the numbers of insulin receptor,increasing the protein of PI3K,and then enhancing the action of insulin signaling pathway;the other was through increasing the protein of AMPK which promoted glucose transport.Moreover hypoxia and/or exercise also increased the gene expression of GLUT4 and GN,which played important roles on promoting muscle glycogen synthesis of hypoxia and/or exercise.
引文
[1].Ivy.JL.Muscle glycogen synthesis before and after exercise.Sports Meds,1991,11:6-9.
[2].Kubo k and Foley JE.Rate-limiting steps for insulin-mediated glucose uptake into perfused rat hindlimb.Am J Physiol,1986,250(1pt 1):E 100-102.
[3]Shulman RG,Bloch G,Rothman DL.In vivo regulation of muscle glycogen synthase and the control of glycogen synthesis.Proc Natl Acad Aci USA,1995,92:8535-8542.
[4].魏守刚.肌糖原生物合成的几种影响因素研究:[博士学位论文].北京:北京体育大学,2001年.
[5].高磊,刘绛光.对葡萄糖转运蛋白的探讨.国外医学临床生物化学与检验学分册,1999,20(6):274-275.
[6].Watson R,Pessin J.Intracellular organization of insulin signaling and GLUT4 translocation..Recent Prog Horm Res,2001,56:175-193.
[7].Bell G,Polonsky k.Diabetes mellitus and genetically programmed defects in β-cell function.Nature,2001,414:788-791.
[8].Zorzano A,Fandos C,Palaci M,et al.Role of plasma membrane transporters in muscle metabolism.Biochem J,2000,349(3):667-688
[9]Marette A,et al.Abundance,location and insulin-induced translocation of glucose transporters in red and white muscle.Am J Physiol,1992,263:C443.
[10].刘传道,江钟立.GLUT4转位和活性的研究进展.中国康复医学杂志,2004,19(4):313-315.
[11]Kemppainen J,Stolen K,Kalliokoski KK,et al.Exercise training improves insulin stimulated Skeletal muscle glucose uptake independent of changes in perfusion in patients with dilated cardiomyopathy.J Card Fail,2003,9(4):286-295.
[12].Douen AG,Ramlal T,Rastogi S,et al.Exercise induces recruitment of the “Insulin-responsive glucose transporter”evidence for distinct instracellular insulin and exercise-recruitable transporter pools in skeletal muscle.J Bio Chem,1990,265:13427
[13].Somwar R,Kim DY,Sweeney G;et al.GLUT4 translocation precedes the stimulation of glucose uptake by insulin in muscle cells:poteintial activation of GLUT4 via p38mitogen-protein kinase.Biochem J,2001,3599pt3):639-649
[14]Sweeney G.Somwar R,Ramlal T,et al.An inhibitor of p38 mitogen-activated protein kinase prevents insulin-stimulated glucose transport but not glucose transporter translocation in 3T3-L1 adipocytes and L6 myotubes.J Biol Chem,1999,274(15):10071 - 10078.
[15].Hayashi T,Hirshman MF,Kurth EJ,et al.Evidence for 5'AMP-activated protein kinase mediation of the effect of muscle contraction on glucose transport.Diabates,1998,49:235-261.
[16]李显,李斌,艾华.骨骼肌葡萄糖转运蛋白4及运动/训练对它的影响.中国运动医学杂志,2004,23(3):329-333.
[17]谷靖,李世昌.运动对葡萄糖转运载体蛋白4基因表达的调控.中国临床康复,2005,9(16):190-191.
[18]LizeanoJM,Alessi DR.The insulin signailing pathway.Curtboil,2002,12(7):R236-334
[19].LeeJ,Pich PE,The insulin receptor;structure,fuction,and signaling.Am J Physiol,1994,266:C319-C334.
[20]Nolan JJ,ludvik B,Baloga J.Mechanisms of the kinetic defect in insulin action in obesity and NIDDM.Diabetes,1997,46:994-1000.
[21].陈东林.胰岛素受体结构及信号转导机制探讨.宜宾师专学报(自然科学版),1998,(2):42-46
[22].范慧.胰岛素受体底物与信号转导.国外医学.生理.病理科学与临床分册,2002,22(5):481-483
[23].陈家伦.胰岛素信号转导及临床意义(上).国外医学内分泌分册,2002,22(1):1-4.
[24]邱定红.磷脂酰肌醇-3激酶研究概况.国外医学遗传学分册,2000,23(1):30-32.
[25]Litherland G,Hajduch E,Hundal H S.Intracellular signaling mechanisms regulating glucose transport in insulin sensitive tissues.Mol Membr Biol,2001,18:195-204.
[26]Kotani K,ogawa W,Hashiramoto M,et al.Inhibition of insulin-induced glucose uptake by atypical protein kinase C isotype-specific interacting protein in 3T3-L1 adipocytes.J boil Chem,2000,275:26390-26395.
[27].Czech M P,corvera S.Signaling mechanisms that regulate glucose transport.J boil Chem,1999,274:1865-1868.
[28].Cantley Lc.The phosphoinositide 3-kinase pathway.Science,2002,296(5573):1655-1657.
[29].刘瑞,白怀,刘秉文.胰岛素受体信号传递.生理科学讲座,2001,32(3):254-256.
[30]胡瑞萍,吴毅,胡永善.运动对糖尿病骨骼肌胰岛素信号传递的影响.中国康复医学杂志,2004,19(9):716-718.
[31].Russell J.W.,Cynthia C.M.,Dan F.L,et al.Activation of motogen-activated protein kinase and phosphatidy linositol,3'-kinase is not sufficient for the hormonal stimulation of glucose uptake,lipogenesis,or glycogen synthesis in 3T3-L1 adipocyte.The Journal of Biological Chemistry,1995,270(7):3442-3446.
[32].Vered Ribon,Alan R S.Insulin stimulates tyrosine phosphorylation of the proto-oncogene product of c-cbl in 3T4-L1 adipocytes.BiOchem J,1997,324:839-846.
[33]杨桂枝.c-Cb1相关蛋白CAP的研究进展.四川解剖学杂志,2004,12(1):36-37.
[34].刘传道等.不同强度的耐力运动对糖尿病大鼠骨骼肌GLUT4mRNA表达的影响.中国康复医学杂志,2005,20(4):244-247
[35].吴毅等.耐力运动对大鼠骨骼肌葡萄糖运载体基因表达的调节作用.中国康复医学杂志,1997,12(4):149-152
[36].吴毅等.耐力运动对大鼠葡萄糖运载体基因表达及转位的影响.中华物理医学与康复杂志,2000,22(2):82-84
[37].杨晓冰等.耐力运动对大鼠骨骼肌细胞葡萄糖运载体的影响.中华物理医学与康复杂志,1999,21(1):17-19
[38].Christ-Roberts CY,Mandarino LJ.Glycogen synthase:key effect of exercise on insulin action.Exerc Sport Sci Rev.2004,32(3):90-94
[39].王从容,杨锡让等.耐力训练对饮食性肥胖大鼠胰岛素作用的影响.中国运动医学杂志,1998,17(1):16-19
[40].丛琳,陈吉棣.运动对糖尿病大鼠糖代谢和胰岛素分泌及受体功能的影响.中国运动医学杂志.2001,20(2):144-145
[41].王从容等.饮食脂肪含量和耐力运动对肥胖鼠胰岛素受体酪氨酸蛋白激酶的影响.体育科学.2001,20(6):51-54
[42].冯光斌等.运动对糖尿病大鼠骨骼肌细胞胰岛素受体的影响.中国运动医学杂志.1998.17(3):209-211
[43].Chibalin AV,Yu M,Ryder JW,et al.Exercise-induced changes in expression and activity of proteins involved in insulin signal transduction in skeletal muscle:differential effects on insulin-receptor substrates 1 and 2.Proc Natl Acad Sci USA.2000,97(1):38-45
[44].Sidney B.Peres,et al.Endurance exercise training increases insulin respon- siveness in isolated adipocytes throught IRS/PI3-kinase/Akt Pathway.J Appl Physiol.2005,98:1037-1043
[45].胡瑞萍,吴毅,胡永善.运动对糖尿病骨骼肌胰岛素信号传递的影响.中国康复医学杂志.2004,19(9):716-718
[46].yu M,biomstrand E,chibalin AV,et al.Marathon running increases ERK1/2 and p38MAP kinase signaling to downstream targets in human skeletal muscle.J physiol,2001,536:273.
[47]Osmann AA,Hancock J,Hunt Dg,et al.Exercise training increases ERK-2 activity skeletal muscle of obese Zucker rats.J Appl Physiol,2001,90(2);454.
[48].江中立等.运动和胰岛素对高血糖大鼠骨骼肌JNK和p38信号传导系统的调节作用.中国康复医学杂志.2003,18(2):69-71
[49].Kei Sakamoto,Laurie J.Goodyear.Exercise effects on muscle insulin signaling and action Invited review:intracellular signaling in contracting skeletal muscle.J Appl Physiol,2002,93:369-383.
[50].Juleen R.Zierath.Exercise Effects of muscle insulim signaling and action invited Review Exercise training-induced changes insulin signaling in skeletal muscle.J appl Physiol.2002,93:773-781.
[51].Jessen N,Goodyer LJ Contraction signaling to glucose transport in skeletal muscle.Jappl Physiol.2005 Jul:99(1):330-337
[52].Hayashi,Tatsuya,JorgenEP.Wojtaszewski,laurieJ.goodyear.Exercise regulation of glucose transport skeletal muscle.Am J Physiol.1997,273:E1039-E1051
[53].Luciana Oquendo Pereira,Antonio Herbert Lancha jr.Exercise of insulin and contraction up on glucose transport in skeletal muscle.progress in Biophysics & Molecular Biology 2004,84:1-27
[54]Lee AD,Hansen PA,Holloszy JO.Wortmainin inhabits insulin-stimulated but not contraction-stimulated glucose transport activity in skeletal muscle.FEBS Lett,1995,361(l):51-54.
[55].Tomas,Eva,Anyonio Zorzano,Neil B.Ruderman.Exercise effects on muscle insulin signaling and action exercise and insulin signaling:a historical perspective.J Appl Physiol.2002,93:765-772
[56].Wojtaszewski,Jorgen FP,Jakob N.Nielsen,Erik A richter..Exercise effects on muscle insulin signaling and action invited review:effect of acute exercise on insulin signaling and action in human.J Appl Physiol.2002,93:384-392
[57].E.A.Richter,J N Nielsen,S.B.Jorgensen,C.Frosigand J.F.P.Wojtaszewski.Signaling to glucose transport in skeletal muscle during exercise,Acta Physiol Scand.2003,178:329-335
[58].Christine Y.Christ,Desmond Hunt,et al.Exercise training improves muscle insulin resistance but not insulin receptor signaling in obese Zucker rats.J Appl Physiol.2002,92:736-744
[59].Polly A.hansen,Lorraine A.Nolte,et al.Increased GLUT4 translicatiion mediates enhanced insulin sensitivity of muscle glucose transport after exercise.J APPl.Physiol,1998,85(4):1218-1222.
[60].David C.Wright,Kathleen A.hucker,John O,et al.Ca~(2+)and AMPK both mediate stimulation of glucose transport by muscle contractions.Diabetes,2004,53:330-335
[61]Rose AJ,Richter EA.Skeletal muscle glucose uptake during exercise:how is it regulated?Physiology(Bethesda).2005,20:260-70.
[62]Wright David C,paige C.Geiger,John O.Holloszy,and Ding-Ho Han.Contraction and hypoxia-stimulated glucose transport is mediated by a Ca~(2+)-dependent mechanism in slow-twitch rat soleus muscle.Am J Physiol Endocrinol Metab 2005,288;E1062-E1066.
[63]Ojuka EO,Jones TE,Nolte LA,Chen M,Wamhoff BR,Sturek M,Holloszy JO.Regulation of GLUT4 biogenesis in muscle:evidence for involvement of AMPK and Ca(2+).Am J Physiol Endocrinol Metab.2002,282(5):E1008-13.
[64]Jian-Ming Ren,et al.Exercise induceds rapid increases in GLUT4 expression,glucose transport capacity,and insulin-stimulated glycogen storage in muscle.The journal of Biological chemistry,1994,269(20):14396-14401.
[65]Xia Xi,Jiahuai Han,and Jin-zhong Zhang.Stimulation of glucose transport by AMP-activated protein kinase via activation of p38 mitogen-activated protein kinase.The Jouanal of biological chemistry,2001,276(44)41029-41034.
[66]Li J,Hu X,Selvakumar P,Russell RR 3rd,Cushman SW,Holman GD,Young LH.Role of the nitric oxide pathway in AMPK-mediated glucose uptake and GLUT4 translocation in heart muscle.Am J Physiol Endocrinol Metab.2004,287(5):E834-41.
[67]蔡明春,黄庆愿．AMPK与能量代谢．重庆医学,2005,34(1)：120-122．
[68]Hudson ER,Pan DA,James J,et al.A novel domain in Amp-activated protein kinase causes glycogen storage bodies similar to those seen in hereditary cardiac arrhythmias.Curr Biol,2003,13(10):861-866.
[69]Polekhia G,Gupta A,Michell B J,et al.AMPK 3 subuint targets metabolic stress sensing to glycogen.Curr Biol,2003,13(10):867-871.
[70]Hansmeier N,Bartels FW,Ros R,et al.Classification of hyper-variable Corynebacterium glutamicum surface-layer proteins by sequence analyses and atomic force microscopy.J Biotechnol,2004,112(1- 2):177-193
[71]Woods,A.,et al.Ca2+/calmodulin-dependent protein kinase kinase-β acts upstream of AMP-activated protein kinase in mammalian cells.Cell Metab,2005,2:21-33.
[72]Hawley,S.A.,et al..Calmodulin-dependent protein kinase kinase-β is an alternative upstream kinase for AMP-activated protein kinase.Cell Metab,2005,2:9-19.
[73]Birnbaum,M.J.2005.Activating AMP-activated protein kinase without AMP.Mol.Cell,19:289-290.
[74]Yun Chau Long and Juleen R.Zierath.AMP-activated protein kinase signaling in metabolic regulation.The Journal of Clinical Investigation,2006,116(7):1776-17
[75]Lemieux K,Konrad D,Klip A,et al.The AMP-activated protein kinase activator AICAR does not induce GLUT4 translocation to transverse tubules but stimulates glucose uptake and p38mitogen-activated protein kinaseαandβin skeletal muscle.FASEB J,2003,17(12):1658-1665.
[76]Balon,T W.Integrative biology of nitric oxide and exercise.Exerc Sport Sci Rev,1999,27:219-253
[77]Fryer,L.G.,Hajduch,E.,Rencurel,F.et al.2000.Activation of glucose transport by AMP-activated protein kinase via stimulation of nitric oxide synthase.Diabetes,49:1978-1985.
[78]Xi,X.,Han,J.& Zhang,J.Z.2001.Stimulation of glucose transport by AMP-activated protein kinase(AMPK) via activation of p38 mitogen-activated protein kinase(MAPK).J Biol Cheam 276,4:1029-34.
[79]Chen,H.C.,Bandyopadhyay,G.,Sajan,M.P.et al.Activation of the ERK pathway and atypical protein kinase C isoforms in exercise- and aminoimidazole-4-carboxamide-1-beta-D -riboside(AICAR)-stimulated glucose transport.J Biol Chem 2002.,277:23554-23562.
[80]Musi N,Goodyear LJ.AMP-activated protein kinase and muscle glucose uptake.Acta Physiol Scand,2003,178(4):337-345.
[81]Sakoda H,Ogihara T,Anai M,et al.Activation of AMPK is essential for AICAR-induced glucose uptake by skeletal muscle but not adipocytes.Am J Physiol Endocrinol Metab.,2002,282(6):E1239-44
[82]Mu J,Brozinick JT Jr,et al.A role for AMP-activated protein kinase in contraction-and hypoxia-regulated glucose transport in skeletal muscle.Mol cell,2001,7(5):1085-1094.
[83]Boning D.Atitude and hypoxia training A short review.Int J Sports Med.1997,18(8):251-63
[84]雷志平.间歇性低氧训练与高原训练的比较研究.西安体育学院学报,1997,14(3):57-61.
[85]Levine B D,Friedman D B,Engfred K,et al.The effects of nomoxic or hypobaricendurance training on the hypoxic ventilatory response.Mde Sci Sports Exe,1992,24:769-775.
[86]Hoppeler H,Vogt M.Hypoxia training for sea-level performance training high-living low.Adv Exp Med Biol,2001,502:61-73.
[87]胡扬.模拟高原训练的新发展--从HiLo到HiHiLo.中国运动医学杂志,2005,24(1):69-72.
[88]赵晋,孔垂辉.亚高原环境对运动训练的影响综述.北京体育大学学报.2005,28(1):78-79
[89]Wilber RL.Current trends in altitude training.Sports Med.2001,31(4):249-65.
[90]黄缄等.缺氧习服后骨骼肌葡萄糖摄取的特点.第三军医大学学报.2004,26(1):5-7.
[91]黄缄等.缺氧习服大鼠骨骼肌葡萄糖运转体特点的研究.第三军医大学学报.2004,26(18):1607-1610.
[92]Chiu LL,Chou SW,Cho YM,et al.Effcet of prolonged intermittent hypoxia and exercise training on glucose tolerance and muscle GLUT4 protein expression in rats.J Biomed sci.2004,11(6):838-846.
[93]Reynoids,et al.GLUT4 glucose transporter expression in rodent brain:effect of diabetes.Brain Res.1998,797(1):1-11
[94]黄缄等.缺氧对大鼠骨骼肌胰岛素受体的影响及其在增强葡萄糖摄取能力中的作用.第三军医大学学报.2005,27(1):9-11.
[95]KolesnykIU,Orestenko IuM.The effect of intermittent hypoxic training on pancreatic endocrine function in animals with diabetes mellitus.Fiziol zh.,1994,40(5-6):87-95
[96]Goodyear L;gorgino F,Balon T,et al.Effects of contractile activity on tyrosine phosphorproteins and PI3-kinase activity in rat skeletal muscle.Am J Physiol,1995,268:E987-995.
[97]Abraham D.Lee,Polly A.Hansen,et al.Wortmannin inhabits insulin-stimulated but not contraction-stimulated glucose transport activity in skeletal muscle.FEBS Letters,1995,361:51-54
[98]Krook A,Wallberg-Henriksson H,Zierath JR.Sending the signal:molecular mechanisms regulating glucose uptake.Med Sci Sports Exerc,2004,36(7):1212-1217.
[99]Cartee GD,Douen AG,Ramlal T,et al.Stimulation of glucose transport in skeletal muscle by hypoxia.J Appl Physiol,1991,70:1593-1600.
[100]Fluckey JD,Ploug T,Galbo H.Mechanism associated with hypoxia- and contractionmediated glucose transport in muscle are fibre-dependent.Acta Physiol Scand,1999,167:83-87.
[101]Wojtaszewski JF,Laustsen J L,Derave L,et al.Hypoxia and contractions do not utilize the same siglaling mechanism in stimulating skeletal muscle glucose transport.Biochim Biophys acta,1998,1380:396-404.
[102]Wim Derave,Peter Hespel.Role of adenosine in regulating glucose uptake during contractions and hypoxia in rat skeletal muscle.Journal of physiology,1999,515(1):255-263.
[103]Reynolds,THomasH,et al.Mechanism of hypoxia-stimulated glucose transport rat skeletal muscle:potential role of glycogen.Exercise training and glucose transport,E773-778
[104]J D Fluckey,T.Ploug,H.Galbo.Mechanisms associated with hypoxia-and contractionmediated glucose transport in muscle are fibre-dependent.Acta Physiol Scand,1999,167: 83-87.
[105]魏守刚,杨则宜,高红.不同运动方式和补剂对大鼠肌糖原生物合成的影响.中国运动医学杂志,2003,22(1):35-40.
[106]刘晔,刘桂华,陈垅.模拟不同海拔高原训练对大鼠骨骼肌蛋白质与糖原含量的影响.山东体育学院学报,1998,14(37):24-30.
[107]翁锡全等.急、慢性缺氧刺激对训练大鼠糖原和血糖的影响.体育学刊,2004,11(2):54-56
[108]黄缄等.缺氧习服大鼠骨骼肌葡萄糖代谢特点研究.西南国防医药,2004,14(5):465-467.
[109]周小梅,马宁等.低氧和低氧游泳大鼠心肌糖原含量与右室功能的变化.中国病理生理杂志,2002,18(1)21-23.
[110]Chou SW,Chiu LL,Cho YM,et al.Effect of systemic hypoxia on GLUT4 Protein expression in exercised rat heart.Jpn J Physiol.,2004,54(4):357-63.
[111]魏守刚,杨则宜等.运动训练和营养补剂对大鼠骨骼肌糖原生成素基因表达的影响.中国运动医学杂志,2005,24(2):143-146.
[112]魏守刚,杨则宜等.训练和补剂对运动后恢复期大鼠骨骼肌糖原合成酶(GS)活性的影响.中国运动医学杂志.2004,23(2):136-141.
[113]周丽斌.胰岛素促葡萄糖转运的调控机制.国外医学内分泌学分册,2003,23(4):276-279
[114]Jeffrey EMarkunts,et al.Insulin and exercise decrease glycogen synthase kinase-3activity by different mechanisms in rat skeletal muscle.The journal of Biological chemistry,1999,274(35)
[115]Eunice Y.Chen,Nathalie M.Mazure,et al.Hypoxia Activates a Platelet-derived Growth Factor Receptor/Phosphatidylinositol 3-Kinase/Akt Pathway That Results in Glycogen Synthase Kinase-3 Inactivationl.CANCER RESEARCH 61,2001,15:2429-2433.
[116]Aschenbach WG,hirshman MF.Fujii N,et al.Effect of AICAR treatment glycogen metabolism in skeletal muscle.Diabetes,2002,51:567-573.
[117]Choi JH,Park MJ,Kim KW,et al.Molecular mechanism of hypoxia-mediated hepatic gluconeogenesis by transcriptional regulation.FEBS Lett.,2005;579(13):2795-801.
[118]谷成英等.运动对2型糖尿病大鼠胰岛细胞形态与功能的影响.中华物理医学与康复杂志,2005,27(3):145-148.
[119]郑陆.力竭性游泳对大鼠胰岛A、B细胞形态学变化的影响-免疫组化及原位分子杂交结果分析.中国运动医学杂志,1997,16(2):95-100.
[120]黄岩,李占淳,石爱荣.外源性胰高血糖素对大鼠胰岛B细胞形态和功能的影响.中国组织化学与细胞化学杂志.2000,9(1):61-64.
[121]鹿国晖.生长激素对运动大鼠胰岛β细胞形态和功能影响的研究.北京体育大学硕士论文,2003年.
[122]吴昊.运动、降糖物质干预对“糖尿病大鼠模型“转归影响的多因素研究.北京体育大学博士论文,2001年.
[123]Shima K,Zhu M,Noma Y,et al.Exercise training in Otsuka Long-Evans Tokushima Fatty rat,a model of spontaneous non-insulin-dependent diabetes mellitus:effects on the B-cell mass,insulin content and fibrosis in the pancreas.Diabetes Res ClinPract,1997,35(1):11-19.
[124]Scheurink A J V.Central and peripheral adrenoceptora affect glucose,free fatty acids and insulin in exercising rats.Am J Physiol,1978,255:547.
[125]Yajima M.An involvement of a-adrenrgic stimulation in exercise-induced hypoglicema.Eur J Pharmacol,1977,42:1-4.
[126]郑陆等,负重力竭性游泳对大鼠血清胰岛素、血糖浓度的影响及胰岛β细胞图象分析.北京体育大学学报,1995,1894):35-39.
[127]Unger RH.Clueagon and A cus.Rcent Prog Horn Res,1997,33:477
[128]曲绵域等,实用运动医学.北京科学技术出版社,1995:63-67
[129]Gambhir KK,Agarwal VR.Red cell insulin receptors in health and disease.biochem Med Biol,1991,45:133-153.
[130]陈小铭等,糖尿病大鼠红细胞和组织胰岛素受体相关性研究.中国药理学通报,1999,4:1-11
[131]Hjollund E,Richelsen B,Pedersen O.Comparative studies of insulin binding to receptor from adipocytes hepatocytes,moncytes and erythrocytes from the pig.Similarities with insulin receptor binding in man.Acta Endocrinol(Copenh),1988,118(1):59-67.
[132]Iwasaki M,Kobayashi M,Ohgaku S,et al.Effect of acute exercise on insulin binding to erythrocytes in type Ⅱ diabetes.Endocrinol Jpn.,1982;29(5):561-566.
[133]Michel G,Vocke T,Fiehn W.Bidirectional alteration of insulin receptor affinity by different forms of physical exercise.Am J Physiol.1984,246(2 Pt 1 ):E 153-159
[134]Webster.Acute exercise epinephrine and diabetes enhance insulin binding to skeletal muscle.AM J Physiol,1986,250(2):E186-197.
[135]Tan MH,Bonen A.Insulin receptors:their roles in the pathogenesis and management of type Ⅱ diabetes mellitus.Ann Acad Med Singapore.1985,14(2):360-363.
[136]Flemaning Dela et al.On the influence of physical training on glucose homeostasis.Acta Physiol scand,1996,158:635.
[137]Soman VR,Koivisto VA,Deibert D.Increased insulin sensitivity and insulin binding to monocytes after physical training.N Engl J Med.,1979,29;301(22):1200-1204.
[138]Lucja S,Franciszek B,Tadeusz R,et al.Binding and degradation of 125I insulin of erythrocyte receptors-effect of physical exertion.Endokrynol Pol.1993,44(2):137-45
[139]Dohm GL,Sinha MK,Caro JF.Insulin receptor binding and protein kinase activity in muscles of trained rats.Am J Physiol.1987 252(2 Pt 1):E170-175.
[140]Santos RF,Mondon CE,Reaven GM.Effects of exercise training on the relationship between insulin binding and insulin-stimulated tyrosine kinase activity in rat skeletal muscle.Metabolism.1989,38(4):376-86.
[141]Kim YB,Inoue T,Nakajima R.Effect of long-term exercise on gene expression of insulin signaling pathway intermediates in skeletal muscle.Biochem Biophys Res Commun.1999, 27(3):720-727.
[142]Wadley GD,Tunstall RJ,Sanigorski A.Differential effects of exercise on insulin-signaling gene expression in human skeletal muscle.J Appl Physiol.2001,90(2):436-440.
[143]Yu m,Blomstrand E,Chibalin AV.Exercise-associated differences in an array of proteins involved in signal transduction and glucose transport.J Appl Physiol.2001,90(1):29-34.
[144]Chibalin AV,Yu M,Ryder JW.Exercise-induced changes in expression and activity of proteins involved in insulin signal transduction in skeletal muscle:differential effects on insulin-receptor substrates 1 and 2.Proc Natl Acad Sci U S A.2000,97(1):38-43.
[145]Tikhonova NE,Kuchuk EM,Shaliapina VG.Hormonal function of the insular apparatus and erythrocyte insulin-binding capacity during adaptation of the rat to high altitude.Fiziol Zh SSSR Im I M Sechenova.l987,73(4):469-474.
[146]Cheng N,Cai W,Jiang M,Wu S.Effect of hypoxia on blood glucose,hormones,and insulin receptor functions in newborn calves.Pediatr Res.l997,41(6):852-856
[147]Christine Y.Christ-Roberts,et al.Increased insulin receptor signaling and glycogen synthase activity contribute to the synergistic effect of exercise on insulin action.J Appl Physiol,2003,95:2519-2529.
[148]Tatsuya hayashi,et al.Evidence for 5'AMP-Activated protein kinase mediation of the effect of muscle contraction on glucose transport.Diabetes,1998,47:1369-1373.
[149]Li J,Hu X,Selvakumar P,et al.Role of the nitric oxide pathway in AMPK-mediated glucose uptake and GLUT4 translocation in heart muscle.Am J Physiol Endocrinol Metab.2004,287(5):E834-841.
[150]Fujii N,Jessen N,Goodyear LJ.AMP-activated protein kinase and the regulation of glucose transport.Am J Physiol Endocrinol Metab.2006,291(5):E867-877.
[151]Fisher JS,Gao J,Han DH,.et al.Activation of AMP kinase enhances sensitivity of muscle glucose transport to insulin.Am J Physiol Endocrinol Metab.2002,282(1):E18-23.
[152]Sriwijitkamol A,Coletta DK,Wajcberg E.Effect of Acute Exercise on AMPK Signaling in Skeletal Muscle of Subjects With Type 2 Diabetes:A Time-Course and Dose-Response Study.Diabetes.2007,56(3):836-848.
[153]Koh HJ,Hirshman MF,He H,et al.Epinephrine is a critical mediator of acute exercise-induced AMP-activated protein kinase activation in adipocytes.Biochem J.2007,26[Epub ahead of print]
[154]Takekoshi K,Fukuhara M,Quin Z.Long-term exercise stimulates adenosine monophosphate-activated protein kinase activity and subunit expression in rat visceral adipose tissue and liver.Metabolism.2006,55(8):1122-8.
[155]Nakano M,Hamada T,Hayashi Talpha2 Isoform-specific activation of 5'adenosine monophosphate-activated protein kinase by 5-aminoimidazole-4-carboxamide-1-beta-d-ribonucleoside at a physiological level activates glucose transport and increases glucose transporter 4 in mouse skeletal muscle.Metabolism.2006,55(3):300-308
[156]Sriwijitkamol A,Ivy JL,Christ-Roberts C.LKB1-AMPK signaling in muscle from obese insulin-resistant Zucker rats and effects of training.Am J Physiol Endocrinol Metab.2006 290(5):E925-932.
[157]Frosig C,Jorgensen SB,Hardie DG 5'-AMP-activated protein kinase activity and protein expression are regulated by endurance training in human skeletal muscle.Am J Physiol Endocrinol Metab.2004,286(3):E411-417.
[158]Nielsen JN,Mustard KJ,Graham DA.5'-AMP-activated protein kinase activity and subunit expression in exercise-trained human skeletal muscle.J Appl Physiol.2003,94(2):631-41.
[159]Steinberg GR,Watt MJ,McGee SL.Reduced glycogen availability is associated with increased AMPKalpha2 activity,nuclear AMPKalpha2 protein abundance,and GLUT4 mRNA expression in contracting human skeletal muscle.Appl Physiol Nutr Metab.2006,31(3):302-12.
[160]Derave W,Ai H,Ihlemann J.Dissociation of AMP-activated protein kinase activation and glucose transport in contracting slow-twitch muscle.Diabetes.2000,49(8):1281-1287.
[161]Yang J,Holman GD.Insulin and contraction stimulate exocytosis,but increased AMP-activated protein kinase activity resulting from oxidative metabolism stress slows endocytosis of GLUT4 in cardiomyocytes.J Biol Chem.2005,280(6):4070-4078.
[162]Mulligan JD,Gonzalez AA,Kumar R.Aging elevates basal adenosine monophosphate-activated protein kinase(AMPK) activity and eliminates hypoxic activation of AMPK in mouse liver.J Gerontol A Biol Sci Med Sci.2005,60(1):21-27.
[163]Frederich M,Zhang L,Balschi JA.Hypoxia and AMP independently regulate AMP-activated protein kinase activity in heart.Am J Physiol Heart Circ Physiol.2005,288(5):H2412-21.
[164]Toyoda T,Hayashi T.Miyamoto L.Possible involvement of the alphal isoform of 5'AMP-activated protein kinase in oxidative stress-stimulated glucose transport in skeletal muscle.Am J Physiol Endocrinol Metab.2004,287(1):E166-73.
[165]Nagata D,Mogi M,Walsh K.AMP-activated protein kinase(AMPK) signaling in endothelial cells is essential for angiogenesis in response to hypoxic stress.J Biol Chem.2003,278(33):31000-31006.
[166]Russell RR 3rd,Bergeron R,Shulman GI.Translocation of myocardial GLUT-4 and increased glucose uptake through activation of AMPK by AICAR.Am J Physiol.1999,277(2 Pt 2):H643-649.
[167]Lee AD,Hansen PA.Holloszy.Wortnanin inhabits insulin-stimulated but not contraction-stimulated glucose transport activity in skeletal muscle.FEBS Lett,1995,361(l):51-54.
[168]Treadway JL,James DE,et al.Effect of exercise on insulin receptor binding and kinase activity in skeletal muscle.Am J Physiol.1989,256(1 Pt 1):E138-44.
[169]Hansen PA,Nolte LA,Chen MM.Increased GLUT-4 translocation mediates enhanced insulin sensitivity of muscle glucose transport after exercise.J Appl Physiol.1998,85(4):1218-22
[170]Kirwan JR del Aguila LF.Regular exercise enhances insulin activation of IRS-1-associated PI3-kinase in human skeletal muscle.J Appl Physiol.2000,88(2):797-803.
[171]Chibalin AV,Yu M,Ryder JW.Exercise-induced changes in expression and activity of proteins involved in insulin signal transduction in skeletal muscle:differential effects on insulin-receptor substrates 1 and 2.Proc Natl Acad Sci U S A.2000,97(1):38-43.
[172]Zhou Q,Dohm GL.Treadmill running increases phosphatidylinostol 3-kinase activity in rat skeletal muscle.Biochem Biophys Res Commun.1997,236(3):647-650.
[173]Risbud MV,Fertala J.Nucleus pulposus cells upregulate PI3K/Akt and MEK/ERK signaling pathways under hypoxic conditions and resist apoptosis induced by serum withdrawal.Spine.2005,30(8):882-889.
[174]Gerasimovskaya EV,Tucker DA,Stenmark KR.Activation of phosphatidylinositol 3-kinase,Akt,and mammalian target of rapamycin is necessary for hypoxia-induced pulmonary artery adventitial fibroblast proliferation.J Appl Physiol.2005,98(2):722-731.
[175]Carini R,Grazia De Cesaris M.Role of phosphatidylinositol 3-kinase in the development of hepatocyte preconditioning.Gastroenterology.2004,127(3):914-923.
[176]Xu L,Pathak PS,Fukumura D.Hypoxia-induced activation of p38 mitogen-activated protein kinase and phosphatidylinositol 3'-kinase signaling pathways contributes to expression of interleukin 8 in human ovarian carcinoma cells.Clin Cancer Res.2004,10(2):701-707.
[177]Alvarez-Tejado M,Alfranca A.Lack of evidence for the involvement of the phosphoinositide 3-kinase/Akt pathway in the activation of hypoxia-inducible factors by low oxygen tension.J Biol Chem.2002,277(16):13508-13517.
[178]杨晓冰等,运动对大鼠葡萄糖运载体基因表达及转位的影响.中华物理医学与康复杂志,200,22(2):82-84.
[179]Kraniou GN,Cameron-Smith D.Acute exercise and GLUT4 expression in human skeletal muscle:influence of exercise intensity.J Appl Physiol.2006,101(3):934-937.
[180]Wu Y,Yang X,Li Y.Exercise induces increased CLUT4 gene expression and protein content in diabetic rats.Zhonghua Yi Xue Za Zhi.2000,80(3):172-174.
[181]Chiu LL,Chou SW,Cho YM.Effect of prolonged intermittent hypoxia and exercise training on glucose tolerance and muscle GLUT4 protein expression in rats.J Biomed Sci.2004 11(6):838-46..
[182]Shearer J,Wilson RJ,Battram DS.Increases in glycogenin and glycogenin mRNA accompany glycogen resynthesis in human skeletal muscle.Am J Physiol Endocrinol Metab.2005,289(3):E508-14.
[183]Kraniou Y,Cameron-Smith D,Misso M.Effects of exercise on GLUT-4 and glycogenin gene expression in human skeletal muscle.J Appl Physiol.2000,88(2):794-796.
[184]Shearer J,Marchand I,Sathasivam P.Glycogenin activity in human skeletal muscle is proportional to muscle glycogen concentration.Am J Physiol Endocrinol Metab.2000,278(1):E177-180.
[185]Christ CY,Hunt D,Hancock J.Exercise training improves muscle insulin resistance but not insulin receptor signaling in obese Zucker rats.J Appl Physiol.2002,92(2):736-744.
[186]Jonathan S.Fisher,Jiaping Gao,et.al.Activition of AMP kinase enhances sensitivity muscle glucose transport to insulin.AM J Physiol Endocrinol Metab,2002,282:E18-E23.
[187]Christine Y.christ,Desmohd Hunt.Exercise training improves muscle insulin resistance but not insulin receptor signaling in obese zucker rats.J Appl Physiol,2002,92:736-744.
[188]Skov-Jensen C,Skovbro M,Flint A.Contraction-mediated glucose uptake is increased in men with impaired glucose tolerance.Appl Physiol Nutr Metab.2007,32(1):115-124.
[189]Fryer LG,Foufelle F,Barnes K.Characterization of the role of the AMP-activated protein kinase in the stimulation of glucose transport in skeletal muscle cells.Biochem J.2002,363(Pt 1):167-174.
[190]MacLean PS,Zheng D,Jones JP.Exercise-induced transcription of the muscle glucose transporter(GLTJT4) gene.Biochem Biophys Res Commun.2002,292(2):409-414.
[191]Jessen N,Pold R,Buhl ES,Effects of AICAR and exercise on insulin-stimulated glucose uptake,signaling,and GLTJT-4 content in rat muscles.J Appl Physiol.2003,94(4):1373-9.
[192]Chen HC,Bandyopadhyay G,Sajan MP.Activation of the ERK pathway and atypical protein kinase C isoforms in exercise-and aminoimidazole-4-carboxamide-l-beta-D-riboside(AICAR)-stimulated glucose transportJ Biol Chem.2002 Jun28;277(26):23554-62.
[193]MacLean PS,Zheng D,Jones JP.Exercise-induced transcription of the muscle glucose transporter(GLUT 4) gene.Biochem Biophys Res Commun.2002,292(2):409-414.
[194]Bergeron R,RR Russell Ⅲ,LHYoung,et al.Effect of AMPk activation on muscle glucose metabolism in conscious rats.am J Physiol,1999,276:E938-E944.
[195]Holmes BF,Kurth-Kraczek EJ,Winder WW.Chronic activation of 5'-AMP-activated protein kinase increases GLUT-4,hexokinase,and glycogen in muscle.J Appl Physiol.1999 87(5):1990-5.
[196]Winder WW.Energy-sensing and signaling by AMP-activated protein kinase in skeletal muscle.J Appl Physiol.2001 Sep;91(3):1017-28
[197]Halse R,Fryer LG,McCormack JG Regulation of glycogen synthase by glucose and glycogen:a possible role for AMP-activated protein kinase.Diabetes.2003,52(1):9-15.
[2].Kubo k and Foley JE.Rate-limiting steps for insulin-mediated glucose uptake into perfused rat hindlimb.Am J Physiol,1986,250(1pt 1):E 100-102.
[3]Shulman RG,Bloch G,Rothman DL.In vivo regulation of muscle glycogen synthase and the control of glycogen synthesis.Proc Natl Acad Aci USA,1995,92:8535-8542.
[4].魏守刚.肌糖原生物合成的几种影响因素研究:[博士学位论文].北京:北京体育大学,2001年.
[5].高磊,刘绛光.对葡萄糖转运蛋白的探讨.国外医学临床生物化学与检验学分册,1999,20(6):274-275.
[6].Watson R,Pessin J.Intracellular organization of insulin signaling and GLUT4 translocation..Recent Prog Horm Res,2001,56:175-193.
[7].Bell G,Polonsky k.Diabetes mellitus and genetically programmed defects in β-cell function.Nature,2001,414:788-791.
[8].Zorzano A,Fandos C,Palaci M,et al.Role of plasma membrane transporters in muscle metabolism.Biochem J,2000,349(3):667-688
[9]Marette A,et al.Abundance,location and insulin-induced translocation of glucose transporters in red and white muscle.Am J Physiol,1992,263:C443.
[10].刘传道,江钟立.GLUT4转位和活性的研究进展.中国康复医学杂志,2004,19(4):313-315.
[11]Kemppainen J,Stolen K,Kalliokoski KK,et al.Exercise training improves insulin stimulated Skeletal muscle glucose uptake independent of changes in perfusion in patients with dilated cardiomyopathy.J Card Fail,2003,9(4):286-295.
[12].Douen AG,Ramlal T,Rastogi S,et al.Exercise induces recruitment of the “Insulin-responsive glucose transporter”evidence for distinct instracellular insulin and exercise-recruitable transporter pools in skeletal muscle.J Bio Chem,1990,265:13427
[13].Somwar R,Kim DY,Sweeney G;et al.GLUT4 translocation precedes the stimulation of glucose uptake by insulin in muscle cells:poteintial activation of GLUT4 via p38mitogen-protein kinase.Biochem J,2001,3599pt3):639-649
[14]Sweeney G.Somwar R,Ramlal T,et al.An inhibitor of p38 mitogen-activated protein kinase prevents insulin-stimulated glucose transport but not glucose transporter translocation in 3T3-L1 adipocytes and L6 myotubes.J Biol Chem,1999,274(15):10071 - 10078.
[15].Hayashi T,Hirshman MF,Kurth EJ,et al.Evidence for 5'AMP-activated protein kinase mediation of the effect of muscle contraction on glucose transport.Diabates,1998,49:235-261.
[16]李显,李斌,艾华.骨骼肌葡萄糖转运蛋白4及运动/训练对它的影响.中国运动医学杂志,2004,23(3):329-333.
[17]谷靖,李世昌.运动对葡萄糖转运载体蛋白4基因表达的调控.中国临床康复,2005,9(16):190-191.
[18]LizeanoJM,Alessi DR.The insulin signailing pathway.Curtboil,2002,12(7):R236-334
[19].LeeJ,Pich PE,The insulin receptor;structure,fuction,and signaling.Am J Physiol,1994,266:C319-C334.
[20]Nolan JJ,ludvik B,Baloga J.Mechanisms of the kinetic defect in insulin action in obesity and NIDDM.Diabetes,1997,46:994-1000.
[21].陈东林.胰岛素受体结构及信号转导机制探讨.宜宾师专学报(自然科学版),1998,(2):42-46
[22].范慧.胰岛素受体底物与信号转导.国外医学.生理.病理科学与临床分册,2002,22(5):481-483
[23].陈家伦.胰岛素信号转导及临床意义(上).国外医学内分泌分册,2002,22(1):1-4.
[24]邱定红.磷脂酰肌醇-3激酶研究概况.国外医学遗传学分册,2000,23(1):30-32.
[25]Litherland G,Hajduch E,Hundal H S.Intracellular signaling mechanisms regulating glucose transport in insulin sensitive tissues.Mol Membr Biol,2001,18:195-204.
[26]Kotani K,ogawa W,Hashiramoto M,et al.Inhibition of insulin-induced glucose uptake by atypical protein kinase C isotype-specific interacting protein in 3T3-L1 adipocytes.J boil Chem,2000,275:26390-26395.
[27].Czech M P,corvera S.Signaling mechanisms that regulate glucose transport.J boil Chem,1999,274:1865-1868.
[28].Cantley Lc.The phosphoinositide 3-kinase pathway.Science,2002,296(5573):1655-1657.
[29].刘瑞,白怀,刘秉文.胰岛素受体信号传递.生理科学讲座,2001,32(3):254-256.
[30]胡瑞萍,吴毅,胡永善.运动对糖尿病骨骼肌胰岛素信号传递的影响.中国康复医学杂志,2004,19(9):716-718.
[31].Russell J.W.,Cynthia C.M.,Dan F.L,et al.Activation of motogen-activated protein kinase and phosphatidy linositol,3'-kinase is not sufficient for the hormonal stimulation of glucose uptake,lipogenesis,or glycogen synthesis in 3T3-L1 adipocyte.The Journal of Biological Chemistry,1995,270(7):3442-3446.
[32].Vered Ribon,Alan R S.Insulin stimulates tyrosine phosphorylation of the proto-oncogene product of c-cbl in 3T4-L1 adipocytes.BiOchem J,1997,324:839-846.
[33]杨桂枝.c-Cb1相关蛋白CAP的研究进展.四川解剖学杂志,2004,12(1):36-37.
[34].刘传道等.不同强度的耐力运动对糖尿病大鼠骨骼肌GLUT4mRNA表达的影响.中国康复医学杂志,2005,20(4):244-247
[35].吴毅等.耐力运动对大鼠骨骼肌葡萄糖运载体基因表达的调节作用.中国康复医学杂志,1997,12(4):149-152
[36].吴毅等.耐力运动对大鼠葡萄糖运载体基因表达及转位的影响.中华物理医学与康复杂志,2000,22(2):82-84
[37].杨晓冰等.耐力运动对大鼠骨骼肌细胞葡萄糖运载体的影响.中华物理医学与康复杂志,1999,21(1):17-19
[38].Christ-Roberts CY,Mandarino LJ.Glycogen synthase:key effect of exercise on insulin action.Exerc Sport Sci Rev.2004,32(3):90-94
[39].王从容,杨锡让等.耐力训练对饮食性肥胖大鼠胰岛素作用的影响.中国运动医学杂志,1998,17(1):16-19
[40].丛琳,陈吉棣.运动对糖尿病大鼠糖代谢和胰岛素分泌及受体功能的影响.中国运动医学杂志.2001,20(2):144-145
[41].王从容等.饮食脂肪含量和耐力运动对肥胖鼠胰岛素受体酪氨酸蛋白激酶的影响.体育科学.2001,20(6):51-54
[42].冯光斌等.运动对糖尿病大鼠骨骼肌细胞胰岛素受体的影响.中国运动医学杂志.1998.17(3):209-211
[43].Chibalin AV,Yu M,Ryder JW,et al.Exercise-induced changes in expression and activity of proteins involved in insulin signal transduction in skeletal muscle:differential effects on insulin-receptor substrates 1 and 2.Proc Natl Acad Sci USA.2000,97(1):38-45
[44].Sidney B.Peres,et al.Endurance exercise training increases insulin respon- siveness in isolated adipocytes throught IRS/PI3-kinase/Akt Pathway.J Appl Physiol.2005,98:1037-1043
[45].胡瑞萍,吴毅,胡永善.运动对糖尿病骨骼肌胰岛素信号传递的影响.中国康复医学杂志.2004,19(9):716-718
[46].yu M,biomstrand E,chibalin AV,et al.Marathon running increases ERK1/2 and p38MAP kinase signaling to downstream targets in human skeletal muscle.J physiol,2001,536:273.
[47]Osmann AA,Hancock J,Hunt Dg,et al.Exercise training increases ERK-2 activity skeletal muscle of obese Zucker rats.J Appl Physiol,2001,90(2);454.
[48].江中立等.运动和胰岛素对高血糖大鼠骨骼肌JNK和p38信号传导系统的调节作用.中国康复医学杂志.2003,18(2):69-71
[49].Kei Sakamoto,Laurie J.Goodyear.Exercise effects on muscle insulin signaling and action Invited review:intracellular signaling in contracting skeletal muscle.J Appl Physiol,2002,93:369-383.
[50].Juleen R.Zierath.Exercise Effects of muscle insulim signaling and action invited Review Exercise training-induced changes insulin signaling in skeletal muscle.J appl Physiol.2002,93:773-781.
[51].Jessen N,Goodyer LJ Contraction signaling to glucose transport in skeletal muscle.Jappl Physiol.2005 Jul:99(1):330-337
[52].Hayashi,Tatsuya,JorgenEP.Wojtaszewski,laurieJ.goodyear.Exercise regulation of glucose transport skeletal muscle.Am J Physiol.1997,273:E1039-E1051
[53].Luciana Oquendo Pereira,Antonio Herbert Lancha jr.Exercise of insulin and contraction up on glucose transport in skeletal muscle.progress in Biophysics & Molecular Biology 2004,84:1-27
[54]Lee AD,Hansen PA,Holloszy JO.Wortmainin inhabits insulin-stimulated but not contraction-stimulated glucose transport activity in skeletal muscle.FEBS Lett,1995,361(l):51-54.
[55].Tomas,Eva,Anyonio Zorzano,Neil B.Ruderman.Exercise effects on muscle insulin signaling and action exercise and insulin signaling:a historical perspective.J Appl Physiol.2002,93:765-772
[56].Wojtaszewski,Jorgen FP,Jakob N.Nielsen,Erik A richter..Exercise effects on muscle insulin signaling and action invited review:effect of acute exercise on insulin signaling and action in human.J Appl Physiol.2002,93:384-392
[57].E.A.Richter,J N Nielsen,S.B.Jorgensen,C.Frosigand J.F.P.Wojtaszewski.Signaling to glucose transport in skeletal muscle during exercise,Acta Physiol Scand.2003,178:329-335
[58].Christine Y.Christ,Desmond Hunt,et al.Exercise training improves muscle insulin resistance but not insulin receptor signaling in obese Zucker rats.J Appl Physiol.2002,92:736-744
[59].Polly A.hansen,Lorraine A.Nolte,et al.Increased GLUT4 translicatiion mediates enhanced insulin sensitivity of muscle glucose transport after exercise.J APPl.Physiol,1998,85(4):1218-1222.
[60].David C.Wright,Kathleen A.hucker,John O,et al.Ca~(2+)and AMPK both mediate stimulation of glucose transport by muscle contractions.Diabetes,2004,53:330-335
[61]Rose AJ,Richter EA.Skeletal muscle glucose uptake during exercise:how is it regulated?Physiology(Bethesda).2005,20:260-70.
[62]Wright David C,paige C.Geiger,John O.Holloszy,and Ding-Ho Han.Contraction and hypoxia-stimulated glucose transport is mediated by a Ca~(2+)-dependent mechanism in slow-twitch rat soleus muscle.Am J Physiol Endocrinol Metab 2005,288;E1062-E1066.
[63]Ojuka EO,Jones TE,Nolte LA,Chen M,Wamhoff BR,Sturek M,Holloszy JO.Regulation of GLUT4 biogenesis in muscle:evidence for involvement of AMPK and Ca(2+).Am J Physiol Endocrinol Metab.2002,282(5):E1008-13.
[64]Jian-Ming Ren,et al.Exercise induceds rapid increases in GLUT4 expression,glucose transport capacity,and insulin-stimulated glycogen storage in muscle.The journal of Biological chemistry,1994,269(20):14396-14401.
[65]Xia Xi,Jiahuai Han,and Jin-zhong Zhang.Stimulation of glucose transport by AMP-activated protein kinase via activation of p38 mitogen-activated protein kinase.The Jouanal of biological chemistry,2001,276(44)41029-41034.
[66]Li J,Hu X,Selvakumar P,Russell RR 3rd,Cushman SW,Holman GD,Young LH.Role of the nitric oxide pathway in AMPK-mediated glucose uptake and GLUT4 translocation in heart muscle.Am J Physiol Endocrinol Metab.2004,287(5):E834-41.
[67]蔡明春,黄庆愿．AMPK与能量代谢．重庆医学,2005,34(1)：120-122．
[68]Hudson ER,Pan DA,James J,et al.A novel domain in Amp-activated protein kinase causes glycogen storage bodies similar to those seen in hereditary cardiac arrhythmias.Curr Biol,2003,13(10):861-866.
[69]Polekhia G,Gupta A,Michell B J,et al.AMPK 3 subuint targets metabolic stress sensing to glycogen.Curr Biol,2003,13(10):867-871.
[70]Hansmeier N,Bartels FW,Ros R,et al.Classification of hyper-variable Corynebacterium glutamicum surface-layer proteins by sequence analyses and atomic force microscopy.J Biotechnol,2004,112(1- 2):177-193
[71]Woods,A.,et al.Ca2+/calmodulin-dependent protein kinase kinase-β acts upstream of AMP-activated protein kinase in mammalian cells.Cell Metab,2005,2:21-33.
[72]Hawley,S.A.,et al..Calmodulin-dependent protein kinase kinase-β is an alternative upstream kinase for AMP-activated protein kinase.Cell Metab,2005,2:9-19.
[73]Birnbaum,M.J.2005.Activating AMP-activated protein kinase without AMP.Mol.Cell,19:289-290.
[74]Yun Chau Long and Juleen R.Zierath.AMP-activated protein kinase signaling in metabolic regulation.The Journal of Clinical Investigation,2006,116(7):1776-17
[75]Lemieux K,Konrad D,Klip A,et al.The AMP-activated protein kinase activator AICAR does not induce GLUT4 translocation to transverse tubules but stimulates glucose uptake and p38mitogen-activated protein kinaseαandβin skeletal muscle.FASEB J,2003,17(12):1658-1665.
[76]Balon,T W.Integrative biology of nitric oxide and exercise.Exerc Sport Sci Rev,1999,27:219-253
[77]Fryer,L.G.,Hajduch,E.,Rencurel,F.et al.2000.Activation of glucose transport by AMP-activated protein kinase via stimulation of nitric oxide synthase.Diabetes,49:1978-1985.
[78]Xi,X.,Han,J.& Zhang,J.Z.2001.Stimulation of glucose transport by AMP-activated protein kinase(AMPK) via activation of p38 mitogen-activated protein kinase(MAPK).J Biol Cheam 276,4:1029-34.
[79]Chen,H.C.,Bandyopadhyay,G.,Sajan,M.P.et al.Activation of the ERK pathway and atypical protein kinase C isoforms in exercise- and aminoimidazole-4-carboxamide-1-beta-D -riboside(AICAR)-stimulated glucose transport.J Biol Chem 2002.,277:23554-23562.
[80]Musi N,Goodyear LJ.AMP-activated protein kinase and muscle glucose uptake.Acta Physiol Scand,2003,178(4):337-345.
[81]Sakoda H,Ogihara T,Anai M,et al.Activation of AMPK is essential for AICAR-induced glucose uptake by skeletal muscle but not adipocytes.Am J Physiol Endocrinol Metab.,2002,282(6):E1239-44
[82]Mu J,Brozinick JT Jr,et al.A role for AMP-activated protein kinase in contraction-and hypoxia-regulated glucose transport in skeletal muscle.Mol cell,2001,7(5):1085-1094.
[83]Boning D.Atitude and hypoxia training A short review.Int J Sports Med.1997,18(8):251-63
[84]雷志平.间歇性低氧训练与高原训练的比较研究.西安体育学院学报,1997,14(3):57-61.
[85]Levine B D,Friedman D B,Engfred K,et al.The effects of nomoxic or hypobaricendurance training on the hypoxic ventilatory response.Mde Sci Sports Exe,1992,24:769-775.
[86]Hoppeler H,Vogt M.Hypoxia training for sea-level performance training high-living low.Adv Exp Med Biol,2001,502:61-73.
[87]胡扬.模拟高原训练的新发展--从HiLo到HiHiLo.中国运动医学杂志,2005,24(1):69-72.
[88]赵晋,孔垂辉.亚高原环境对运动训练的影响综述.北京体育大学学报.2005,28(1):78-79
[89]Wilber RL.Current trends in altitude training.Sports Med.2001,31(4):249-65.
[90]黄缄等.缺氧习服后骨骼肌葡萄糖摄取的特点.第三军医大学学报.2004,26(1):5-7.
[91]黄缄等.缺氧习服大鼠骨骼肌葡萄糖运转体特点的研究.第三军医大学学报.2004,26(18):1607-1610.
[92]Chiu LL,Chou SW,Cho YM,et al.Effcet of prolonged intermittent hypoxia and exercise training on glucose tolerance and muscle GLUT4 protein expression in rats.J Biomed sci.2004,11(6):838-846.
[93]Reynoids,et al.GLUT4 glucose transporter expression in rodent brain:effect of diabetes.Brain Res.1998,797(1):1-11
[94]黄缄等.缺氧对大鼠骨骼肌胰岛素受体的影响及其在增强葡萄糖摄取能力中的作用.第三军医大学学报.2005,27(1):9-11.
[95]KolesnykIU,Orestenko IuM.The effect of intermittent hypoxic training on pancreatic endocrine function in animals with diabetes mellitus.Fiziol zh.,1994,40(5-6):87-95
[96]Goodyear L;gorgino F,Balon T,et al.Effects of contractile activity on tyrosine phosphorproteins and PI3-kinase activity in rat skeletal muscle.Am J Physiol,1995,268:E987-995.
[97]Abraham D.Lee,Polly A.Hansen,et al.Wortmannin inhabits insulin-stimulated but not contraction-stimulated glucose transport activity in skeletal muscle.FEBS Letters,1995,361:51-54
[98]Krook A,Wallberg-Henriksson H,Zierath JR.Sending the signal:molecular mechanisms regulating glucose uptake.Med Sci Sports Exerc,2004,36(7):1212-1217.
[99]Cartee GD,Douen AG,Ramlal T,et al.Stimulation of glucose transport in skeletal muscle by hypoxia.J Appl Physiol,1991,70:1593-1600.
[100]Fluckey JD,Ploug T,Galbo H.Mechanism associated with hypoxia- and contractionmediated glucose transport in muscle are fibre-dependent.Acta Physiol Scand,1999,167:83-87.
[101]Wojtaszewski JF,Laustsen J L,Derave L,et al.Hypoxia and contractions do not utilize the same siglaling mechanism in stimulating skeletal muscle glucose transport.Biochim Biophys acta,1998,1380:396-404.
[102]Wim Derave,Peter Hespel.Role of adenosine in regulating glucose uptake during contractions and hypoxia in rat skeletal muscle.Journal of physiology,1999,515(1):255-263.
[103]Reynolds,THomasH,et al.Mechanism of hypoxia-stimulated glucose transport rat skeletal muscle:potential role of glycogen.Exercise training and glucose transport,E773-778
[104]J D Fluckey,T.Ploug,H.Galbo.Mechanisms associated with hypoxia-and contractionmediated glucose transport in muscle are fibre-dependent.Acta Physiol Scand,1999,167: 83-87.
[105]魏守刚,杨则宜,高红.不同运动方式和补剂对大鼠肌糖原生物合成的影响.中国运动医学杂志,2003,22(1):35-40.
[106]刘晔,刘桂华,陈垅.模拟不同海拔高原训练对大鼠骨骼肌蛋白质与糖原含量的影响.山东体育学院学报,1998,14(37):24-30.
[107]翁锡全等.急、慢性缺氧刺激对训练大鼠糖原和血糖的影响.体育学刊,2004,11(2):54-56
[108]黄缄等.缺氧习服大鼠骨骼肌葡萄糖代谢特点研究.西南国防医药,2004,14(5):465-467.
[109]周小梅,马宁等.低氧和低氧游泳大鼠心肌糖原含量与右室功能的变化.中国病理生理杂志,2002,18(1)21-23.
[110]Chou SW,Chiu LL,Cho YM,et al.Effect of systemic hypoxia on GLUT4 Protein expression in exercised rat heart.Jpn J Physiol.,2004,54(4):357-63.
[111]魏守刚,杨则宜等.运动训练和营养补剂对大鼠骨骼肌糖原生成素基因表达的影响.中国运动医学杂志,2005,24(2):143-146.
[112]魏守刚,杨则宜等.训练和补剂对运动后恢复期大鼠骨骼肌糖原合成酶(GS)活性的影响.中国运动医学杂志.2004,23(2):136-141.
[113]周丽斌.胰岛素促葡萄糖转运的调控机制.国外医学内分泌学分册,2003,23(4):276-279
[114]Jeffrey EMarkunts,et al.Insulin and exercise decrease glycogen synthase kinase-3activity by different mechanisms in rat skeletal muscle.The journal of Biological chemistry,1999,274(35)
[115]Eunice Y.Chen,Nathalie M.Mazure,et al.Hypoxia Activates a Platelet-derived Growth Factor Receptor/Phosphatidylinositol 3-Kinase/Akt Pathway That Results in Glycogen Synthase Kinase-3 Inactivationl.CANCER RESEARCH 61,2001,15:2429-2433.
[116]Aschenbach WG,hirshman MF.Fujii N,et al.Effect of AICAR treatment glycogen metabolism in skeletal muscle.Diabetes,2002,51:567-573.
[117]Choi JH,Park MJ,Kim KW,et al.Molecular mechanism of hypoxia-mediated hepatic gluconeogenesis by transcriptional regulation.FEBS Lett.,2005;579(13):2795-801.
[118]谷成英等.运动对2型糖尿病大鼠胰岛细胞形态与功能的影响.中华物理医学与康复杂志,2005,27(3):145-148.
[119]郑陆.力竭性游泳对大鼠胰岛A、B细胞形态学变化的影响-免疫组化及原位分子杂交结果分析.中国运动医学杂志,1997,16(2):95-100.
[120]黄岩,李占淳,石爱荣.外源性胰高血糖素对大鼠胰岛B细胞形态和功能的影响.中国组织化学与细胞化学杂志.2000,9(1):61-64.
[121]鹿国晖.生长激素对运动大鼠胰岛β细胞形态和功能影响的研究.北京体育大学硕士论文,2003年.
[122]吴昊.运动、降糖物质干预对“糖尿病大鼠模型“转归影响的多因素研究.北京体育大学博士论文,2001年.
[123]Shima K,Zhu M,Noma Y,et al.Exercise training in Otsuka Long-Evans Tokushima Fatty rat,a model of spontaneous non-insulin-dependent diabetes mellitus:effects on the B-cell mass,insulin content and fibrosis in the pancreas.Diabetes Res ClinPract,1997,35(1):11-19.
[124]Scheurink A J V.Central and peripheral adrenoceptora affect glucose,free fatty acids and insulin in exercising rats.Am J Physiol,1978,255:547.
[125]Yajima M.An involvement of a-adrenrgic stimulation in exercise-induced hypoglicema.Eur J Pharmacol,1977,42:1-4.
[126]郑陆等,负重力竭性游泳对大鼠血清胰岛素、血糖浓度的影响及胰岛β细胞图象分析.北京体育大学学报,1995,1894):35-39.
[127]Unger RH.Clueagon and A cus.Rcent Prog Horn Res,1997,33:477
[128]曲绵域等,实用运动医学.北京科学技术出版社,1995:63-67
[129]Gambhir KK,Agarwal VR.Red cell insulin receptors in health and disease.biochem Med Biol,1991,45:133-153.
[130]陈小铭等,糖尿病大鼠红细胞和组织胰岛素受体相关性研究.中国药理学通报,1999,4:1-11
[131]Hjollund E,Richelsen B,Pedersen O.Comparative studies of insulin binding to receptor from adipocytes hepatocytes,moncytes and erythrocytes from the pig.Similarities with insulin receptor binding in man.Acta Endocrinol(Copenh),1988,118(1):59-67.
[132]Iwasaki M,Kobayashi M,Ohgaku S,et al.Effect of acute exercise on insulin binding to erythrocytes in type Ⅱ diabetes.Endocrinol Jpn.,1982;29(5):561-566.
[133]Michel G,Vocke T,Fiehn W.Bidirectional alteration of insulin receptor affinity by different forms of physical exercise.Am J Physiol.1984,246(2 Pt 1 ):E 153-159
[134]Webster.Acute exercise epinephrine and diabetes enhance insulin binding to skeletal muscle.AM J Physiol,1986,250(2):E186-197.
[135]Tan MH,Bonen A.Insulin receptors:their roles in the pathogenesis and management of type Ⅱ diabetes mellitus.Ann Acad Med Singapore.1985,14(2):360-363.
[136]Flemaning Dela et al.On the influence of physical training on glucose homeostasis.Acta Physiol scand,1996,158:635.
[137]Soman VR,Koivisto VA,Deibert D.Increased insulin sensitivity and insulin binding to monocytes after physical training.N Engl J Med.,1979,29;301(22):1200-1204.
[138]Lucja S,Franciszek B,Tadeusz R,et al.Binding and degradation of 125I insulin of erythrocyte receptors-effect of physical exertion.Endokrynol Pol.1993,44(2):137-45
[139]Dohm GL,Sinha MK,Caro JF.Insulin receptor binding and protein kinase activity in muscles of trained rats.Am J Physiol.1987 252(2 Pt 1):E170-175.
[140]Santos RF,Mondon CE,Reaven GM.Effects of exercise training on the relationship between insulin binding and insulin-stimulated tyrosine kinase activity in rat skeletal muscle.Metabolism.1989,38(4):376-86.
[141]Kim YB,Inoue T,Nakajima R.Effect of long-term exercise on gene expression of insulin signaling pathway intermediates in skeletal muscle.Biochem Biophys Res Commun.1999, 27(3):720-727.
[142]Wadley GD,Tunstall RJ,Sanigorski A.Differential effects of exercise on insulin-signaling gene expression in human skeletal muscle.J Appl Physiol.2001,90(2):436-440.
[143]Yu m,Blomstrand E,Chibalin AV.Exercise-associated differences in an array of proteins involved in signal transduction and glucose transport.J Appl Physiol.2001,90(1):29-34.
[144]Chibalin AV,Yu M,Ryder JW.Exercise-induced changes in expression and activity of proteins involved in insulin signal transduction in skeletal muscle:differential effects on insulin-receptor substrates 1 and 2.Proc Natl Acad Sci U S A.2000,97(1):38-43.
[145]Tikhonova NE,Kuchuk EM,Shaliapina VG.Hormonal function of the insular apparatus and erythrocyte insulin-binding capacity during adaptation of the rat to high altitude.Fiziol Zh SSSR Im I M Sechenova.l987,73(4):469-474.
[146]Cheng N,Cai W,Jiang M,Wu S.Effect of hypoxia on blood glucose,hormones,and insulin receptor functions in newborn calves.Pediatr Res.l997,41(6):852-856
[147]Christine Y.Christ-Roberts,et al.Increased insulin receptor signaling and glycogen synthase activity contribute to the synergistic effect of exercise on insulin action.J Appl Physiol,2003,95:2519-2529.
[148]Tatsuya hayashi,et al.Evidence for 5'AMP-Activated protein kinase mediation of the effect of muscle contraction on glucose transport.Diabetes,1998,47:1369-1373.
[149]Li J,Hu X,Selvakumar P,et al.Role of the nitric oxide pathway in AMPK-mediated glucose uptake and GLUT4 translocation in heart muscle.Am J Physiol Endocrinol Metab.2004,287(5):E834-841.
[150]Fujii N,Jessen N,Goodyear LJ.AMP-activated protein kinase and the regulation of glucose transport.Am J Physiol Endocrinol Metab.2006,291(5):E867-877.
[151]Fisher JS,Gao J,Han DH,.et al.Activation of AMP kinase enhances sensitivity of muscle glucose transport to insulin.Am J Physiol Endocrinol Metab.2002,282(1):E18-23.
[152]Sriwijitkamol A,Coletta DK,Wajcberg E.Effect of Acute Exercise on AMPK Signaling in Skeletal Muscle of Subjects With Type 2 Diabetes:A Time-Course and Dose-Response Study.Diabetes.2007,56(3):836-848.
[153]Koh HJ,Hirshman MF,He H,et al.Epinephrine is a critical mediator of acute exercise-induced AMP-activated protein kinase activation in adipocytes.Biochem J.2007,26[Epub ahead of print]
[154]Takekoshi K,Fukuhara M,Quin Z.Long-term exercise stimulates adenosine monophosphate-activated protein kinase activity and subunit expression in rat visceral adipose tissue and liver.Metabolism.2006,55(8):1122-8.
[155]Nakano M,Hamada T,Hayashi Talpha2 Isoform-specific activation of 5'adenosine monophosphate-activated protein kinase by 5-aminoimidazole-4-carboxamide-1-beta-d-ribonucleoside at a physiological level activates glucose transport and increases glucose transporter 4 in mouse skeletal muscle.Metabolism.2006,55(3):300-308
[156]Sriwijitkamol A,Ivy JL,Christ-Roberts C.LKB1-AMPK signaling in muscle from obese insulin-resistant Zucker rats and effects of training.Am J Physiol Endocrinol Metab.2006 290(5):E925-932.
[157]Frosig C,Jorgensen SB,Hardie DG 5'-AMP-activated protein kinase activity and protein expression are regulated by endurance training in human skeletal muscle.Am J Physiol Endocrinol Metab.2004,286(3):E411-417.
[158]Nielsen JN,Mustard KJ,Graham DA.5'-AMP-activated protein kinase activity and subunit expression in exercise-trained human skeletal muscle.J Appl Physiol.2003,94(2):631-41.
[159]Steinberg GR,Watt MJ,McGee SL.Reduced glycogen availability is associated with increased AMPKalpha2 activity,nuclear AMPKalpha2 protein abundance,and GLUT4 mRNA expression in contracting human skeletal muscle.Appl Physiol Nutr Metab.2006,31(3):302-12.
[160]Derave W,Ai H,Ihlemann J.Dissociation of AMP-activated protein kinase activation and glucose transport in contracting slow-twitch muscle.Diabetes.2000,49(8):1281-1287.
[161]Yang J,Holman GD.Insulin and contraction stimulate exocytosis,but increased AMP-activated protein kinase activity resulting from oxidative metabolism stress slows endocytosis of GLUT4 in cardiomyocytes.J Biol Chem.2005,280(6):4070-4078.
[162]Mulligan JD,Gonzalez AA,Kumar R.Aging elevates basal adenosine monophosphate-activated protein kinase(AMPK) activity and eliminates hypoxic activation of AMPK in mouse liver.J Gerontol A Biol Sci Med Sci.2005,60(1):21-27.
[163]Frederich M,Zhang L,Balschi JA.Hypoxia and AMP independently regulate AMP-activated protein kinase activity in heart.Am J Physiol Heart Circ Physiol.2005,288(5):H2412-21.
[164]Toyoda T,Hayashi T.Miyamoto L.Possible involvement of the alphal isoform of 5'AMP-activated protein kinase in oxidative stress-stimulated glucose transport in skeletal muscle.Am J Physiol Endocrinol Metab.2004,287(1):E166-73.
[165]Nagata D,Mogi M,Walsh K.AMP-activated protein kinase(AMPK) signaling in endothelial cells is essential for angiogenesis in response to hypoxic stress.J Biol Chem.2003,278(33):31000-31006.
[166]Russell RR 3rd,Bergeron R,Shulman GI.Translocation of myocardial GLUT-4 and increased glucose uptake through activation of AMPK by AICAR.Am J Physiol.1999,277(2 Pt 2):H643-649.
[167]Lee AD,Hansen PA.Holloszy.Wortnanin inhabits insulin-stimulated but not contraction-stimulated glucose transport activity in skeletal muscle.FEBS Lett,1995,361(l):51-54.
[168]Treadway JL,James DE,et al.Effect of exercise on insulin receptor binding and kinase activity in skeletal muscle.Am J Physiol.1989,256(1 Pt 1):E138-44.
[169]Hansen PA,Nolte LA,Chen MM.Increased GLUT-4 translocation mediates enhanced insulin sensitivity of muscle glucose transport after exercise.J Appl Physiol.1998,85(4):1218-22
[170]Kirwan JR del Aguila LF.Regular exercise enhances insulin activation of IRS-1-associated PI3-kinase in human skeletal muscle.J Appl Physiol.2000,88(2):797-803.
[171]Chibalin AV,Yu M,Ryder JW.Exercise-induced changes in expression and activity of proteins involved in insulin signal transduction in skeletal muscle:differential effects on insulin-receptor substrates 1 and 2.Proc Natl Acad Sci U S A.2000,97(1):38-43.
[172]Zhou Q,Dohm GL.Treadmill running increases phosphatidylinostol 3-kinase activity in rat skeletal muscle.Biochem Biophys Res Commun.1997,236(3):647-650.
[173]Risbud MV,Fertala J.Nucleus pulposus cells upregulate PI3K/Akt and MEK/ERK signaling pathways under hypoxic conditions and resist apoptosis induced by serum withdrawal.Spine.2005,30(8):882-889.
[174]Gerasimovskaya EV,Tucker DA,Stenmark KR.Activation of phosphatidylinositol 3-kinase,Akt,and mammalian target of rapamycin is necessary for hypoxia-induced pulmonary artery adventitial fibroblast proliferation.J Appl Physiol.2005,98(2):722-731.
[175]Carini R,Grazia De Cesaris M.Role of phosphatidylinositol 3-kinase in the development of hepatocyte preconditioning.Gastroenterology.2004,127(3):914-923.
[176]Xu L,Pathak PS,Fukumura D.Hypoxia-induced activation of p38 mitogen-activated protein kinase and phosphatidylinositol 3'-kinase signaling pathways contributes to expression of interleukin 8 in human ovarian carcinoma cells.Clin Cancer Res.2004,10(2):701-707.
[177]Alvarez-Tejado M,Alfranca A.Lack of evidence for the involvement of the phosphoinositide 3-kinase/Akt pathway in the activation of hypoxia-inducible factors by low oxygen tension.J Biol Chem.2002,277(16):13508-13517.
[178]杨晓冰等,运动对大鼠葡萄糖运载体基因表达及转位的影响.中华物理医学与康复杂志,200,22(2):82-84.
[179]Kraniou GN,Cameron-Smith D.Acute exercise and GLUT4 expression in human skeletal muscle:influence of exercise intensity.J Appl Physiol.2006,101(3):934-937.
[180]Wu Y,Yang X,Li Y.Exercise induces increased CLUT4 gene expression and protein content in diabetic rats.Zhonghua Yi Xue Za Zhi.2000,80(3):172-174.
[181]Chiu LL,Chou SW,Cho YM.Effect of prolonged intermittent hypoxia and exercise training on glucose tolerance and muscle GLUT4 protein expression in rats.J Biomed Sci.2004 11(6):838-46..
[182]Shearer J,Wilson RJ,Battram DS.Increases in glycogenin and glycogenin mRNA accompany glycogen resynthesis in human skeletal muscle.Am J Physiol Endocrinol Metab.2005,289(3):E508-14.
[183]Kraniou Y,Cameron-Smith D,Misso M.Effects of exercise on GLUT-4 and glycogenin gene expression in human skeletal muscle.J Appl Physiol.2000,88(2):794-796.
[184]Shearer J,Marchand I,Sathasivam P.Glycogenin activity in human skeletal muscle is proportional to muscle glycogen concentration.Am J Physiol Endocrinol Metab.2000,278(1):E177-180.
[185]Christ CY,Hunt D,Hancock J.Exercise training improves muscle insulin resistance but not insulin receptor signaling in obese Zucker rats.J Appl Physiol.2002,92(2):736-744.
[186]Jonathan S.Fisher,Jiaping Gao,et.al.Activition of AMP kinase enhances sensitivity muscle glucose transport to insulin.AM J Physiol Endocrinol Metab,2002,282:E18-E23.
[187]Christine Y.christ,Desmohd Hunt.Exercise training improves muscle insulin resistance but not insulin receptor signaling in obese zucker rats.J Appl Physiol,2002,92:736-744.
[188]Skov-Jensen C,Skovbro M,Flint A.Contraction-mediated glucose uptake is increased in men with impaired glucose tolerance.Appl Physiol Nutr Metab.2007,32(1):115-124.
[189]Fryer LG,Foufelle F,Barnes K.Characterization of the role of the AMP-activated protein kinase in the stimulation of glucose transport in skeletal muscle cells.Biochem J.2002,363(Pt 1):167-174.
[190]MacLean PS,Zheng D,Jones JP.Exercise-induced transcription of the muscle glucose transporter(GLTJT4) gene.Biochem Biophys Res Commun.2002,292(2):409-414.
[191]Jessen N,Pold R,Buhl ES,Effects of AICAR and exercise on insulin-stimulated glucose uptake,signaling,and GLTJT-4 content in rat muscles.J Appl Physiol.2003,94(4):1373-9.
[192]Chen HC,Bandyopadhyay G,Sajan MP.Activation of the ERK pathway and atypical protein kinase C isoforms in exercise-and aminoimidazole-4-carboxamide-l-beta-D-riboside(AICAR)-stimulated glucose transportJ Biol Chem.2002 Jun28;277(26):23554-62.
[193]MacLean PS,Zheng D,Jones JP.Exercise-induced transcription of the muscle glucose transporter(GLUT 4) gene.Biochem Biophys Res Commun.2002,292(2):409-414.
[194]Bergeron R,RR Russell Ⅲ,LHYoung,et al.Effect of AMPk activation on muscle glucose metabolism in conscious rats.am J Physiol,1999,276:E938-E944.
[195]Holmes BF,Kurth-Kraczek EJ,Winder WW.Chronic activation of 5'-AMP-activated protein kinase increases GLUT-4,hexokinase,and glycogen in muscle.J Appl Physiol.1999 87(5):1990-5.
[196]Winder WW.Energy-sensing and signaling by AMP-activated protein kinase in skeletal muscle.J Appl Physiol.2001 Sep;91(3):1017-28
[197]Halse R,Fryer LG,McCormack JG Regulation of glycogen synthase by glucose and glycogen:a possible role for AMP-activated protein kinase.Diabetes.2003,52(1):9-15.