耐力训练对高脂膳食大鼠以及GK大鼠骨骼肌PGC-1α、ERRα和NRF-2基因表达的影响
|
摘要
糖尿病是各种致病因子作用于机体导致胰岛功能减退、胰岛素抵抗等而引发的糖、蛋白质、脂肪、水和电解质等一系列代谢紊乱综合征,也是全世界发病率和病死率最高的5种疾病之一。胰岛素抵抗与糖尿病之间有着密切的联系,在Ⅱ型糖尿病患者当中,高达90%的患者机体内出现了IR。后天性的高脂膳食和先天性的遗传糖尿病都会引起胰岛素抵抗指数的提高。长期耐力运动能够促进线粒体生物发生,提高线粒体功能,不但能够缓解高脂膳食对机体的负作用,还能对糖尿病患者的机体起到积极的改善效果。
PGC-1α是体内的一种转录共同激活因子,在肌纤维类型的转化、葡萄糖代谢、脂肪酸氧化以及线粒体生物发生等方面起着重要的调节作用；ERRa是PGC-1α的重要效应器,被PGC-1α激活后能够扩大PGC-1α的级联效应,同样在机体能量代谢和线粒体生物发生方面有着重要的作用；NRF-2受到PGC-1α、ERRa的调控,是与呼吸链表达有关的重要转录调节蛋白因子。当受到刺激时,可能通过PGC-1α-ERRa-NRF-2信号通路诱导线粒体的生物发生,从而产生适应性的改变以维持机体健康。
目的：研究耐力训练在不同膳食、糖尿病病理条件下大鼠骨骼肌PGC-1α、ERR、、NRF-2基因表达的影响,探讨耐力训练对机体线粒体生物发生和呼吸链的影响、对高脂膳食机体内胰岛素抵抗以及对先天性Ⅱ型糖尿病患者病情的影响机制。
方法：将40只雄性SD大鼠,4周龄,体重100±5g随机分成SD普通膳食对照组(C)、SD普通膳食耐力训练组(E)、SD高脂膳食对照组(H)、SD高脂膳食耐力训练组(HE),每组10只；同时将12只雄性GK大鼠,8周龄,体重250±5g随机分成GK对照组(G)和GK耐力运动组(GE),每组6只。SD耐力运动组大鼠和GK耐力运动组大鼠分别进行8周和6周跑台训练,每周训练6天,每天一次,起始跑速为13m/min,最大速度不超过16.7m/min,SD耐力运动组前四周每天训练40分钟,后四周每天训练1小时。GK耐力运动组第1周训练30分钟,2周后逐渐递增至1小时,并保持3周。经过饲养,末次运动结束24-48h内处死各组大鼠,测大鼠血糖和血清胰岛素水平,计算胰岛素抵抗指数反映胰岛素抵抗情况Real-time PCR测定鼠骨骼肌PGC-1、mRNA、ERRαmRNA和NRF-2 mRNA水平。
结果：
(1)体重：高脂膳食会显著提高SD大鼠的体重；耐力训练能够有效的控制由于高脂膳食所导致的体重增长,但对GK大鼠体重无显著性影响。
(2)胰岛素抵抗指数：高脂膳食显著提高SD大鼠胰岛素抵抗指数；耐力训练能够显著降低高脂膳食SD大鼠和GK大鼠的血糖水平以及胰岛素抵抗指数；
(3)高脂膳食对SD大鼠骨骼肌PGC-1α、ERRα与NRF-2 mRNA均未产生显著性影响。
(4)耐力训练显著降低高脂膳食SD大鼠和GK大鼠骨骼肌内PGC-1αmRNA的表达。
(5)耐力训练显著降低GK大鼠骨骼肌内ERRα和NRF-2 mRNA的表达,但未对高脂膳食SD大鼠骨骼肌内ERRα和NRF-2 mRNA产生显著影响。
结论：
(1)耐力训练可以显著控制高脂膳食大鼠体重增长速度；
(2)无论是后天性高脂膳食,还是先天性糖尿病所导致的胰岛素抵抗水平过高的现象,都可以通过耐力运动得到缓解。
(3)耐力训练会降低GK大鼠骨骼肌内PGC-1α、ERRα与NRF-2 mRNA的表达,并降低高脂膳食SD大鼠PGC-1αmRNA的表达。耐力运动对PGC-1α、ERRα和NRF-2 mRNA的影响机制,还需要进一步的研究。
Diabetes is a series of metabolic disorder syndrome induced by a variety of pathogenic factors acting on the body leading to islet dysfunction and insulin resistance,and metabolic disorder of glucose、protein、fat、water and electrolytes. It's also one of the diseases with highest morbidity and mortality. Insulin resistance and diabetes are closely linked, in type 2 diabetes patients, up to 90% of the body there were symptoms of insulin resistance. The the improvement of insulin resistance index could be caused either by the acquired a high-fat diet or the congenital genetic diabetes.The long-term endurance exercise can promote the biosynthesis of mitochondria、improve mitochondrial function,not only can alleviate the negative effects of High-fat diet on the body, but also have a positive improvement in the diabetic patients.
PGC-1αis a transcriptional co-activator factor in vivo,and plays an important role in the regulation of in the transformation of muscle fiber type, glucose metabolism, fatty acid oxidation and mitochondrial biosynthesis; ERRa is an important effect device of PGC-la when activated by PGC-1α,ERRa would expand the cascade effect of PGC-1α, so it Also plays an important role in the body energy metabolism and mitochondrial bio-synthesis;NRF-2, which mediated by PGC-1αand ERRa, regulates the expression of important transcription regulatory protein factor in the respiratory chain. When are stimulated, PGC-la-ERRa-NRF-2 pathway may induce the biosynthesis of mitochondria to generate adaptive stress, in order to maintain the body's health.
Objective:The aim of this study was to investigate the effects of endurance training on the expression of PGC-la,ERRa, NRF-2 genes in the high-fat diet rats, as well as GK rats' skeletal muscle;the effects of endurance exercise on the body's biological synthesis, the high-fat diet bodys'insulin resistance, and the effect on congenital diabetes disease.
Methods:The 40 male SD rats,about 4 weeks old,weighing 100±5g were randomly divided into SD normal diet control group (C),SD ordinary diet endurance training group(E),SD high-fat diet the control group (H) and SD high-fat diet endurance training group (HE), n=10 each group;At the same time 12 GK male rats, about 8 weeks of age, weighing 250±5g were randomly divided into GK control group (G), and GK endurance exercise group (GE),n=6 each group.SD endurance exercise rats take 8 weeks of treadmill training, while GK endurance exercise rats take 6 weeks, training six days a week, starting with a speed of of 13m/min, a maximum speed of no more than 16.7m/min.At first, SD endurance exercise rats takes four weeks training 40 minutes a day training, then takesl h/day training for four weeks.GK endurance exercise rats take a 30 minutes'training at the first week, then in the next two weeks, the training time gradually adds to 60 minutes and keeps for 3weeks.The rats were killed in the time during 24～48 hours after the last time exercise.Detected the blood glucose and plasma insulin levels in each group, the situation of insulin resistance were reflected by insulin resistance index.mRNA levels of PGC-1α,ERRa and NRF-2 of rats'skeletal muscle were determined using real-time PCR.
Results:
(1)Body Weight:High-fat diet can significantly improve the body weight.Endurance exercise can effectly control the weight gain caused by high-fat diet, but don't have significantly effect on the GK rats'weight-gainning.
(2)Insulin Resistance Index:Endurance exercise can significantly reduce the level of blood glucose level and insulin resistance index of high-fat diet rats and the GK rats;
(3)High-fat diet has no significant effect on the expression of PGC-1α, ERRa and NRF-2 mRNA in the SD rats'muscle.
(4)Endurance exercise significantly reduces the expression of PGC-1αmRNA in the high-fat diet SD rats and GK rats'skeletal muscle;
(5)Endurance exercise significantly reduces the expression of ERRa and NRF-2 mRNA in the GK rats'skeletal muscle, while has no significant effect on the expression of ERRa and NRF-2 mRNA in the high-fat diet rats'skeletal muscle
Conclusion:
(1)Endurance training can significantly control the body weight increase of the high-fat diet-rats
(2)Endurance exercise can alleviate the too high-expressed-insulin resistance index, no matter it's caused by the high-fat diet or the congenital diabetes mellitus
(3)Endurance exercise can reduce the expression of PGC-1α, ERRa and NRF-2 mRNA in the GK rat skeletal muscle, and reduce the expression of PGC-1αmRNA in the high-fat diet rats.We need to do further study to know the mechanism that the affect of endurance exercise on the mRNA expression of PGC-1α, ERRa and NRF-2.
PGC-1α是体内的一种转录共同激活因子,在肌纤维类型的转化、葡萄糖代谢、脂肪酸氧化以及线粒体生物发生等方面起着重要的调节作用；ERRa是PGC-1α的重要效应器,被PGC-1α激活后能够扩大PGC-1α的级联效应,同样在机体能量代谢和线粒体生物发生方面有着重要的作用；NRF-2受到PGC-1α、ERRa的调控,是与呼吸链表达有关的重要转录调节蛋白因子。当受到刺激时,可能通过PGC-1α-ERRa-NRF-2信号通路诱导线粒体的生物发生,从而产生适应性的改变以维持机体健康。
目的：研究耐力训练在不同膳食、糖尿病病理条件下大鼠骨骼肌PGC-1α、ERR、、NRF-2基因表达的影响,探讨耐力训练对机体线粒体生物发生和呼吸链的影响、对高脂膳食机体内胰岛素抵抗以及对先天性Ⅱ型糖尿病患者病情的影响机制。
方法：将40只雄性SD大鼠,4周龄,体重100±5g随机分成SD普通膳食对照组(C)、SD普通膳食耐力训练组(E)、SD高脂膳食对照组(H)、SD高脂膳食耐力训练组(HE),每组10只；同时将12只雄性GK大鼠,8周龄,体重250±5g随机分成GK对照组(G)和GK耐力运动组(GE),每组6只。SD耐力运动组大鼠和GK耐力运动组大鼠分别进行8周和6周跑台训练,每周训练6天,每天一次,起始跑速为13m/min,最大速度不超过16.7m/min,SD耐力运动组前四周每天训练40分钟,后四周每天训练1小时。GK耐力运动组第1周训练30分钟,2周后逐渐递增至1小时,并保持3周。经过饲养,末次运动结束24-48h内处死各组大鼠,测大鼠血糖和血清胰岛素水平,计算胰岛素抵抗指数反映胰岛素抵抗情况Real-time PCR测定鼠骨骼肌PGC-1、mRNA、ERRαmRNA和NRF-2 mRNA水平。
结果：
(1)体重：高脂膳食会显著提高SD大鼠的体重；耐力训练能够有效的控制由于高脂膳食所导致的体重增长,但对GK大鼠体重无显著性影响。
(2)胰岛素抵抗指数：高脂膳食显著提高SD大鼠胰岛素抵抗指数；耐力训练能够显著降低高脂膳食SD大鼠和GK大鼠的血糖水平以及胰岛素抵抗指数；
(3)高脂膳食对SD大鼠骨骼肌PGC-1α、ERRα与NRF-2 mRNA均未产生显著性影响。
(4)耐力训练显著降低高脂膳食SD大鼠和GK大鼠骨骼肌内PGC-1αmRNA的表达。
(5)耐力训练显著降低GK大鼠骨骼肌内ERRα和NRF-2 mRNA的表达,但未对高脂膳食SD大鼠骨骼肌内ERRα和NRF-2 mRNA产生显著影响。
结论：
(1)耐力训练可以显著控制高脂膳食大鼠体重增长速度；
(2)无论是后天性高脂膳食,还是先天性糖尿病所导致的胰岛素抵抗水平过高的现象,都可以通过耐力运动得到缓解。
(3)耐力训练会降低GK大鼠骨骼肌内PGC-1α、ERRα与NRF-2 mRNA的表达,并降低高脂膳食SD大鼠PGC-1αmRNA的表达。耐力运动对PGC-1α、ERRα和NRF-2 mRNA的影响机制,还需要进一步的研究。
Diabetes is a series of metabolic disorder syndrome induced by a variety of pathogenic factors acting on the body leading to islet dysfunction and insulin resistance,and metabolic disorder of glucose、protein、fat、water and electrolytes. It's also one of the diseases with highest morbidity and mortality. Insulin resistance and diabetes are closely linked, in type 2 diabetes patients, up to 90% of the body there were symptoms of insulin resistance. The the improvement of insulin resistance index could be caused either by the acquired a high-fat diet or the congenital genetic diabetes.The long-term endurance exercise can promote the biosynthesis of mitochondria、improve mitochondrial function,not only can alleviate the negative effects of High-fat diet on the body, but also have a positive improvement in the diabetic patients.
PGC-1αis a transcriptional co-activator factor in vivo,and plays an important role in the regulation of in the transformation of muscle fiber type, glucose metabolism, fatty acid oxidation and mitochondrial biosynthesis; ERRa is an important effect device of PGC-la when activated by PGC-1α,ERRa would expand the cascade effect of PGC-1α, so it Also plays an important role in the body energy metabolism and mitochondrial bio-synthesis;NRF-2, which mediated by PGC-1αand ERRa, regulates the expression of important transcription regulatory protein factor in the respiratory chain. When are stimulated, PGC-la-ERRa-NRF-2 pathway may induce the biosynthesis of mitochondria to generate adaptive stress, in order to maintain the body's health.
Objective:The aim of this study was to investigate the effects of endurance training on the expression of PGC-la,ERRa, NRF-2 genes in the high-fat diet rats, as well as GK rats' skeletal muscle;the effects of endurance exercise on the body's biological synthesis, the high-fat diet bodys'insulin resistance, and the effect on congenital diabetes disease.
Methods:The 40 male SD rats,about 4 weeks old,weighing 100±5g were randomly divided into SD normal diet control group (C),SD ordinary diet endurance training group(E),SD high-fat diet the control group (H) and SD high-fat diet endurance training group (HE), n=10 each group;At the same time 12 GK male rats, about 8 weeks of age, weighing 250±5g were randomly divided into GK control group (G), and GK endurance exercise group (GE),n=6 each group.SD endurance exercise rats take 8 weeks of treadmill training, while GK endurance exercise rats take 6 weeks, training six days a week, starting with a speed of of 13m/min, a maximum speed of no more than 16.7m/min.At first, SD endurance exercise rats takes four weeks training 40 minutes a day training, then takesl h/day training for four weeks.GK endurance exercise rats take a 30 minutes'training at the first week, then in the next two weeks, the training time gradually adds to 60 minutes and keeps for 3weeks.The rats were killed in the time during 24～48 hours after the last time exercise.Detected the blood glucose and plasma insulin levels in each group, the situation of insulin resistance were reflected by insulin resistance index.mRNA levels of PGC-1α,ERRa and NRF-2 of rats'skeletal muscle were determined using real-time PCR.
Results:
(1)Body Weight:High-fat diet can significantly improve the body weight.Endurance exercise can effectly control the weight gain caused by high-fat diet, but don't have significantly effect on the GK rats'weight-gainning.
(2)Insulin Resistance Index:Endurance exercise can significantly reduce the level of blood glucose level and insulin resistance index of high-fat diet rats and the GK rats;
(3)High-fat diet has no significant effect on the expression of PGC-1α, ERRa and NRF-2 mRNA in the SD rats'muscle.
(4)Endurance exercise significantly reduces the expression of PGC-1αmRNA in the high-fat diet SD rats and GK rats'skeletal muscle;
(5)Endurance exercise significantly reduces the expression of ERRa and NRF-2 mRNA in the GK rats'skeletal muscle, while has no significant effect on the expression of ERRa and NRF-2 mRNA in the high-fat diet rats'skeletal muscle
Conclusion:
(1)Endurance training can significantly control the body weight increase of the high-fat diet-rats
(2)Endurance exercise can alleviate the too high-expressed-insulin resistance index, no matter it's caused by the high-fat diet or the congenital diabetes mellitus
(3)Endurance exercise can reduce the expression of PGC-1α, ERRa and NRF-2 mRNA in the GK rat skeletal muscle, and reduce the expression of PGC-1αmRNA in the high-fat diet rats.We need to do further study to know the mechanism that the affect of endurance exercise on the mRNA expression of PGC-1α, ERRa and NRF-2.
引文
.http://baike.baidu.com/view/923.htm.
[2]KingH, Aubert R E, Herman WH, et al.Global burden of diabetes. 1995-2025,prevalence numerical estmiates and projections [J].Diabetes Care,1998,21(9):1414-1431.
[3]文立,马国栋.运动与骨骼肌线粒体生物发生[J].中国运动医学杂志,2005,24(4)：484-488.
[4]Michael, Gaster. Insulin resistance and the mitochondrial link. Lessons from cultured human myotubes [J].Biochimica et Biophysica Acta,2007,1772(7): 755-765
[5]Hojlund K, Wrzesinski K, Larsen PM, et al.Proteome analysis reveals phosphorylation of ATP synthase beta-subunit in human skeletal muscle and proteins with potential roles in type 2 diabetes.J Biol Chem 2003; 278 (12):10436-42
[6]Morino K, Petersen KF, Dufour S,et al.Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents.J Clin Invest 2005; 115 (12):3587-93
[7]Petersen KF, Dufour S,Befroy D, et al.Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes.N Engl J Med 2004; 350 (7):664-71
[8]Befroy DE, Petersen KF, Dufour S,et al.Impaired mitochondrial substrate oxidation in muscle of insulin-resistant offspring of type 2 diabetic patients.Diabetes 2007; 56 (5):1376-81
[9]张燕,王强,王东进.能量代谢与疾病的关键调控因子PGC-1α(下)[J].中国糖尿病杂志,2008,16(8)：453-458.
[10]路中PGC-1α与糖尿病血糖代谢[J].国外医学老年医学分册,2003,24(3)：106-108.
[11]Patti ME, Butte AJ,Crunkhorn S,et al.coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes:Potential role of PGC-1 and NRF-1[J].Proc Natl Acad Sci USA,2003,100:8466-8471.
[12]Keith Baar. Involvement of PPAR Y co-activator-1,nuclear respiratory factors 1 and 2,and PPAR Y in the adaptive response to endurance exercise[J].Proceedings of the Nutrition Society,2004(63):269-273.
[13]王芬,何华亮,刘铜华.自发的2型糖尿病动物模型[J].中国实验动物学报,2007,15(5)：395-398.
[14]Goto Y,Kakizaki M.The spontaneous—diabetes rat:a model of non-insulin-dependent diabetes mellitus.Proc Jpn Aead,1981,57:381-384.
[15]Guru Y,Suzuki K,Sasaki M,Ono T,et al.GK rat as a mode 1 of non-obese, non-insulin—dependent diabetes:selective breeding over 35 generations.In Shafrir E,Renold AE (Eds).Frontiers in Diabetes Research.Lessons from Animal Diabetes Ⅱ.London:Libbey 1988,301-303.
[16]Bisbis S,Bailbe D,Tormo MA,et al.Insulin resistance in the GK rat: decreased receptor number but normal kinase activity in the liver.Am J Physiol, 1993.265:807-813.
[17]Ostenson CG,Khan A,Abdel—Halim SM.et al,Abnormal insulin secretion aim glucose metabolism in pancreatic islets from the spontaneously diabetic GK rat.Diabetologia,1993,36:3-8.
[18]Movassat J,Shinier C,Serradas P,et al.Impaired development of pancreatic beta—cell mass is a primary event during the progression to diabetes in the GK rat.Diabetologia,1997,40(8):916-925.
[19]Berthelier C,Kergoat M,Portha B.Lack of deterioration of insulin action with aging in the GK rat:a contrasted adaptation as compared with non-diabetic rat.Metabolism,1997,46(8):890—896.
[20]Gill—Randall RI,ADAMS D,Ollerton RL,et al.Is human type 2 diabetes masternally inherited?Insights from an animal model[J].Diabetic Medicine,2004, 21:759—762.
[21]徐倍,吴国亭等.2型糖尿病GK大鼠病程进展与组织形态学改变[J].同济大学学报(医学版),2007,28(5)：17-21.
[22]张丽萍,荣海钦,季虹等。2型糖尿病模型G K大鼠骨形态学和生物力学特点观察[J].中国实验动物学报,2008,16(5)：361-365.
[23]Spiegelman BM, and Heinrich R.Biological control through regulated transcriptional coactivators.Cell,2004,119:157-167.
[24]张燕,王强,王东进.能量代谢与疾病的关键调控因子PGC-1a(上)[J].中国糖尿病杂志,2008,16(7)：385-388.
[25]Puigserver P, Wu Z, Spiegelman BM, et al.A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis [J].Cell,1998,9:829-839.
[26]Lin J,Puigserver P, Donovan J, et al.Peroxisome proliferator-activated receptor γ coactivator 1β(PGC-1β), a novel PGC-1-related transcription coactivator associated with host cell factor. J Biol Chem,2002,277:1645-1648.
[27]Kressler D,Schreiber SN, Knutti D, et al.The PGC-1-related protein PERC is a selective coactivator of estrogen receptor a. J Biol Chem,2002,277:13918-13925.
[28]Andersson U, Scarpulla RC.Pgc-1-related coactivator, a novel,serum-inducible coactivator of nuclear respiratory factor 1-dependent transcription in mammalian cells. Mol Cell Biol,2001,21:3738-3749.
[29]Knutti D, Kaul A, Kralli A. A tissue-specific coactivator of steroid receptors, identified in a functional genetic screen.Mol Cell Biol,2000,20:2411-242
[30]Wallberg AE, Yamamura S,Malik S,et al.Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through coactivator PGC-1alpha. Mol Cell,2003,12:1137-114
[31]Leone TC, Lehman JJ,Finck BN, et al.PGC-lalpha deficiency causes multisystem energy metabolic derangements:muscle dysfunction, abnormal weight control and hepatic steatosis.PLoS Biol,2005,3:e101.
[32]Lin J,Yang R,Tarr PT, et al.Hyperlipidemic effects of dietary saturated fats mediated through PGC-lbeta coactivation of SREBP. Cell,2005,120:261-273.
[33]Lin J,Handschin C, Spiegelman BM. Metabolic control through the PGC-1 family transcription coactivators.Cell Metab,2005,1:361-370.
[34]Kawakami Y, Tsuda M,Takahashi S,et al.Transcriptional coactivator PGC-1{alpha} regulates chondrogenesis via association with Sox9·Proc Natl Acad Sci USA,2005,102:2414-2419.
[35]Brian N.Daniel P. Kelly. PGC-1 coactivators:inducible regulators of energy metabolism in health and disease [J].The Journal of Clinical Investigation. 2006.116(3):615-622.
[36]Lin J,Handschin C, Spiegelman BM.Metabolic control through the PGC-1 family transcription coactivators.Cell Metab,2005,1:361-370.
[37]Tiraby C,Tavernier G, Lefort C, et al.Acquirement of brown fat cell features by human white adipocytes.J Biol Chem,2003,278:33370-33376
[38]Michael LF, Wu Z,Cheatham RB,et al.Restoration of insulin-sensitive glucose transporter (GLUT4) gene expression in muscle cells bythe transcriptional coactivator PGC-1·Proc Natl Acad Sci USA,2001,98:3820-3825.
[39]Lehman JJ, Barger PM, Kovacs A, et al.Peroxisome proliferator-activated recep tor gamma coactivator-1 promotes cardiac mitochondrial biogenesis[J].J Clin Invest, 2000,106 (7):847-856.
[40]Bernal-Mizrachi C, Weng S,Feng C,et al.Dexamethasone induction of hypertension and diabetes is PPAR-a dependent in LDL receptor-null mice.Nat Med, 2003,9:1069-1075.
[41]Koo SH, Satoh H, Herzig S,et al.PGC-1 promotes insulin resistance in liver through PPARa-dependent induction of TRB-3-Nat Med,2004,10:530-534.
[42]Handschin C, Lin J, Rhee J,et al.Nutritional regulation of hepatic heme biosynthesis and porphyria through PGC-la. Cell,2005,122:505-515.
[43]Zurlo F, Larson K, Bogardus C,et al.Skeletal muscle metabolism is a major determinant of resting energy expenditure.J Clin Invest,1990,86:1423-1427.
[44]Zurlo F,Nemeth PM,Choksi RM,et al.Whole-body energy metabolism and skeletal muscle biochemical characteristics.Metabolism,1994,43:481-486.
[45]Lin J,Wu H, Tarr PT, et al.Transcriptional coactivator PGC-1α drives the for mation of slow-twitch muscle fibres [J].Nature,2002,418 (6899):797-801.
[46]路文盛,颜晓东,黄勤等PGC-1α基因MEF2C结构域482G/A变异参与2型糖尿病发病的机制研究[J].中华医学遗传学杂志,2008.25(6)：
[47]Wu Z, Puigserver P, AnderssonU,et al.Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1.Cell,1999,98: 115-124.
[48]Montoya J,Perez-Martos A and Garstka HL. Regulation ofmitochondrial transcription by mitochondrial transcription factor A. Mol Cell Biochem,1997,174: 227-230.
[49]Mao S,Leone TC,Kelly DP,et al.Mitochondrial transcription factor A is increased but expression of ATP synthase bet subunit and medium-chain acyl-CoA dehydrogenase gene are decreased in hearts of copper-deficient rats[J].J Nutr,2000,130:2143-2150.
[50]赵玉琼,陈华PGC-1基因与Ⅱ型糖尿病[J].实验动物科学,2008,25(6)：45-47.
[51]Yamamoto T, ShimanoH, Nakagawa Y,et al.SREBP-1 interacts with hepatocyte nuclear factor-4 alpha and interferes with PGC-1 recruitment to suppress hepatic gluconeogenic genes.J Biol Chem,2004,279:12027-12035.
[52]Yoon JC, Puigserver P, Chen G, et al.Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1·Nature,2001,413:131-138.
[53]Lowell BB,Shulman GI. Mitochondrial dysfunction and type 2 diabetes[J]. Science,2005,307:3842387.
[54]Kelley DE, He J,Menshikova EV,et al.Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes[J].Diabetes,2002,51:2944-2950.
[55]Giguere V, Yang N, Segui P, et al.Identification of a new class of steroid hormone receptors.Nature,1988,331(6151):91-94.
[56]Hong H, Yang L, Stallcup M R.Hormone-independent transcriptional activation and coactivator binding by novel orphan nuclear receptor ERRa.J Biol Chem,1999, 274(32):22618-22626.
[57]钱云霞,钱凯.先雌激素相关受ERR的功能及其调控.生物化学与生物物理进展,2005,32(6)：495-500.
[58]Sladek R,Beatty B,Squire J.Chromosomal mapping of the human and murine orphan receptors ERRa(ESRRA) and ERRβ(ESRRB) and identification of a novel human ERRa-related pseudogene.Genomics,1997,45(2):320～326.
[59]Feng W,Ribeiro,RC,Wagner R L,et al.Hormone-dependent coactivator binding to a hydrophobic cleft on nuclear receptors.Science,1998,280(5370): 1747-1749.
[60]Horard B,Vanacker J M. Estrogen receptor-related receptors:orphan receptors desperately seeking a ligand.J Mol Endocrinol,2003,31(3):349-357.
[61]Johnston S D,Liu X,Zuo F,et al.Estrogen—related receptor alfunctionally binds as a monomer to extended half-site sequences including ones contained、vithill estrogen—response elements.Mol Endocrinol,1997,11(3):342-352.
[62]赵丕文,牛建昭等.雌激素相关受体及其在雌激素信号转导体系中的作用.生命的化学,2008,28(5)：579-582.
[63]Hentschke M, Susens U,Borgmeyer U.PGC-1 and PERC,coactivators of the estrogen-receptor—related receptor.Biochem Biophys Res Commun,2002,299(5): 872～879.
[64]Heard DJ, Peder L. Norby, Jim Holloway, et al.Human ERRy, a Third Member of the Estrogen Receptor-Related Receptor (ERR) Subfamily of Orphan Nuclear Receptors:Tissue-Specific Isoforms Are Expressed during Development and in the Adult._Mol Endocrinol,2000,14(3):382-392
[65]Stein RA, McDonnell.Estrogen-related receptor aas a therapeutic target in cancer.Endocr Relat Cancer,2006,13(1):S25-S32
[66]Huss J M,Kopp RP,Kelly DP.PGC-la coactivates the cardiac—enriched nuclear receptor ERRα and γ via novel leucine-rich interaction interfaces.J Biol Chem,2002,277(43):40265-40274.
[67]Bonnelye E, Kung V, Laplace C, et al.Estrogen receptor-related receptor alpha impinges on the estrogen axis in bone:potential function in osteoporosis. Endocrinology,2002,143(9):3658-3670.
[68]Bonnelye E, Merdad L, Kung V, et al.The orphan nuclear estrogen receptor-related receptor a is expressed throughout osteoblast differentiation and regulates bone formation in vitro.J Cell Biol,2001,153(5):971-984.
[69]Kraus RJ, Ariazi EA, Farrell ML, et al.Estrogen-related receptor alpha 1 actively antagonizes estrogen receptor-regulated transcription in MCF-7 mammary cells.J Biol Chem,2002,277(27):24826-24834.
[70]Suzuki T, Miki Y, Moriya T, Shimada et al.Estrogen-related receptor alpha in human breast carcinoma as a potent prognostic factor. Cancer Research.2004(64):4670-4676
[71]Schreiber S N, Knutti D, Brogli K et al.The transcriptional coactivator PGC—1 regulates the expression and activity of the orphan nuclear receptor ERRa.J Biol Chem,2003,278(11):9013-9018.
[72]Carrier J C,Deblois G,Champigny C,et al.Estrogen related receptor a.is a transcriptional regulator of apolipoprotein A-IV and controls lipid handling in the intestine.J Biol Chem,2004,279(50):52052～52058.
[73]Adam R,Janice M, Paul J,et al.PGC-la Coactivates PDK4 Gene Expression via the Orphan Nuclear Receptor ERRa:a Mechanism for Transcriptional Control of Muscle Glucose Metabolism.Mol.Cell Biol,2005,25(24):10684-10694.
[74]Sylvia N, Roger Emter, Benjamin H,et al.The estrogen-related receptor a (ERRa)functions in PPARγ coactivator 1α (PGC-1α)-induced mitochondrial biogenesis.PNAS,2004,101(17):6472-6477.
[75]陈锐.核呼吸因子研究进展[J].国外医学·生理、病理科学与临床分册,2005,25(1)：59-61.
[76]Scarpulla RC. Nuclear activators and coactivators in mammalian mitochondrial biogenesis[J].Biochim BiophysActa,2002,1576(1-2):1-14.
[77]C. S.Kraft, C. M. R.LeMoine, C. N. Lyons, et al.Control of mitochondrial biogenesis during myogenesis [J].Am J Physiol Cell Physiol,2006; 290(4):C1119-C1127.
[78]江海洪.细胞核对线粒体呼吸链功能调控的研究[J].国外医学·生理、病理科学与临床分册,2001,21(3)：167-169.
[79]Davies KJ,PackerL and Brooks GA. Biochemical adaptation of mitochondria, muscle, and whole-animal respiration to endurance training[J].Arch Biochem Biophys,1981,209:539-554.
[80]赵婷婷,丁树哲,大鼠游泳运动后骨骼肌PGC-1 a mRNA表达的时相性变化[J],上海体育学院学报,第30卷第3期,2006年5月,4144.
[81]Akimoto T,Steven C,Pohnert,et al.Exercise Stimulates Pge-1 Transcription in.Skeletal Muscle through Activation of the p38 MAPK Pathway[J].Biol Chem, 2005,280:19587-19593.
[82]Goto M, Terada S,Kato M, et al.cDNA Cloning and mRNA analysis of PGC-1 in epitrochlearis muscle in swimming-exercised rats.Biochem Biophys Res Commun 2000; 274 (2):350-4
[83]Bengtsson J, Gustafsson T, Widegren U,et al.Mitochondrial transcription factor A and respiratory complex IV increase in response to exercise training in humans. Pflugers Arch 2001; 443(1):61-6
[84]62.Gordon JW, Rungi AA, Inagaki H, et al.Effects of contractile activity on mitochondrial transcription factor A expression in skeletal muscle.J Appl Physiol 2001; 90 (1):389-96
[85]Baar K, Wende AR,Jones TE, et al.Adaptations of skeletal muscle to exercise: rapid increase in the transcriptional coactivator PGC-1.Faseb J 2002; 16 (14): 1879-86
[86]Pilegaard H, Saltin B,Neufer PD.Exercise induces transient transcriptional activation of the PGC-lalpha gene in human skeletal muscle.J Physiol 2003;546 (Pt 3):851-8
[87]Cartoni R, Leger B, Hock MB,et al.Mitofusins 1/2 and ER-Ralpha expression are increased in human skeletal muscle after physical exercise. J Physiol 2005;567 (Pt 1):349-58
[88].Garnier A, Fortin D, Zoll J, et al.Coordinated changes in mitochondrial function and biogenesis in healthy and diseased human skeletal muscle.Faseb J 2005; 19 (1): 43-52
[89]Mahoney DJ,Parise G,Melov S,et al.Analysis of global mRNA expression in human skeletal muscle during recovery from endurance exercise.Faseb J 2005; 19 (11):1498-500
[90]Russell AP, Hesselink MK, Lo SK, et al.Regulation of metabolic transcriptional co-activators and transcription factors with acute exercise.Faseb J 2005;19 (8):986-8
[91]Terada S,Kawanaka K, Goto M, et al.Effects of high-intensity intermittent swimming on PGC-1alpha protein expression in rat skeletal muscle.Acta Physiol Scand 2005; 184 (1):59-65
[92]Adhihetty PJ,Taivassalo T, Haller RG,et al.The effect of training on the expression of mitochondrial biogenesis-and apoptosis-related proteins in skeletal muscle of patients with mtDNA defects.Am J Physiol Endocrinol Metab 2007; 293 (3):E672-80
[93]Wright DC, Han DH, Garcia-Roves PM, et al.Exercise-induced mitochondrial biogenesis begins before the increase in muscle PGC-1alpha expression. J Biol Chem 2007; 282 (1):194-9
[94]Jose A Lumini, Jose Magalhaes, Paulo J,et al.Beneficial Effects of Exercise on Muscle Mitochondrial Function in Diabetes Mellitus.[J] Sports Med 2008; 38 (9): 735-750.
[95]Wu H, Kanatous SB,Thurmond FA,et al.Regulation of mitochondrial biogenesis in skeletal muscle by CaMK[J].Science,2002,296:349-352.
[96]Handschin C,Rhee J,Lin J,et al.An auto-regulatory loop controls peroxisome proliferator-activated receptor gamma coactivator 1alpha expression in muscle.[J] Proc Natl Acad Sci USA,2003,100:7111-711
[97]Zong H, Ren JM,Y oung LH, et al.AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation[J].Proc Natl Acad Sci USA,2002,99:15983-15987.
[1]百度百科-糖尿病http://baike.baidu.com/view/923.htm.
[2]Hevener AL, Reichart D,Olefsky J,et al.Thiazolidinedione treatment prevents free fatty acid-induced insulin resistance in male wister rats[J].Diabetes,2001,50(10): 2316-2322.
[3]文立,马国栋.运动与骨骼肌线粒体生物发生[J].中国运动医学杂志,2005,24(4)：484-488.
[4]Morino K, Petersen KF, Dufour S,et al.Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents.J Clin Invest 2005; 115 (12):3587-93
[5]Petersen KF, Dufour S,Befroy D, et al.Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes.N Engl J Med 2004; 350 (7):664-71
[6]Befroy DE, Petersen KF, Dufour S,et al.Impaired mitochondrial substrate oxidation in muscle of insulin-resistant offspring of type 2 diabetic patients.Diabetes 2007; 56 (5):1376-81
[7]张燕,王强,王东进.能量代谢与疾病的关键调控因子PGC-1α(下)[J].中国糖尿病杂志,2008,16(8)：453-458.
[8]路中.PGC-1α与糖尿病血糖代谢[J].国外医学老年医学分册,2003,24(3)：106-108.
[9]Brian N. Daniel P.Kelly. PGC-1 coactivators:inducible regulators of energy metabolism in health and disease[J].The Journal of Clinical Investigation.2006.116(3):615-622.
[10]Sylvia N, Roger Emter, Benjamin H, et al.The estrogen-related receptor a (ERRa) functions in PPARy coactivator 1α(PGC-1α)-induced mitochondrial biogenesis. PNAS,2004,101(17):6472-6477.
[11]陈锐.核呼吸因子研究进展[J].国外医学·生理、病理科学与临床分册,2005,25(1)：59-61.
[12]Davies KJ, PackerL and Brooks GA. Biochemical adaptation of mitochondria, muscle, and whole-animal respiration to endurance training[J].Arch Biochem Biophys,1981,209:539-554.
[13]Jose A Lumini,Jose Magalhaes, Paulo J, et al.Beneficial Effects of Exercise on Muscle Mitochondrial Function in Diabetes Mellitus.[J] Sports Med 2008; 38 (9): 735-750.
[14]Schrauwen P,Westerterp KR.The role of high-fat diets and physical activity in the regulation of body weight[J].British Journal of Nutrition,2000,84(4):417-427.
[15]李翠珍,赵刚.耐力训练对雄性高脂膳食大鼠脂代谢异常及胰岛素水平的影响.辽宁大学学报.自然科学版.2008.35(4)：363-366
[16]百度百科-胰岛素http://baike.baidu.com/view/1340.htm.
[17]许斯华,金文胜,林延.2型糖尿病血糖与胰岛素释放关系的探讨第一军医大学学报2003；23(8)：859-862.
[18]维基百科-胰岛素抵抗http://zh.wikipedia.org/wiki/胰岛素抵抗.
[19]默里 RK,格兰纳DK,迈耶斯PA等,宋惠萍等译.哈珀生物化学(第25版)[M].科学出版社,2003.
[20]Silva da RC，Miranda WL,Chacra AR,et al.Insulin resistance,beta-cellfunction, and glucose tolerance in Brazilian adolescents with obesity or risk factors for type 2 diabetes mellitus[J].Journal of Diabetes and its Complications,2007,21(2):84-92.
[21]Litherland GJ,Morris NJ,Walker M, et al.Role of glycogen content in insulin resistance in human muscle cells[J].Cell Physiol,2007,211(2):344-352.
[22]Joris Hoeks, Jacob J.Briede, Johan de Vogel.Mitochondrial function, content and ROS production in rat skeletal muscle:Effect of high-fat feeding[J].FEBS Letters,2008,582(5):510-516.
[23]Unger R H.Lipotoxicity of cells in obesity and in other causes of fatty acid spillover [J]. Diabetes,2001,50(Suppll):518-521.
[24]S.Iwashita, MamoruTanida et.al.Decreased skeletal muscle insulin receptors in high-fat diet-related hypertensive rats.1./NutritionResearch22(2002)1049-1053
[25]胰岛素受体学说与Ⅱ型糖尿病胰岛素抵抗http://age.bjmu.cn/old/progress/pbl/07.pdf
[26]陈丹,毕会民,毕欣,运动对胰岛素抵抗大鼠骨骼集中糖原合成酶激酶-3表达的影响[J].中华物理医学与康复杂志,2006,28(3)：153—156.
[27]Berthelier C,Kergoat M,Portha B.Lack of deterioration of insulin action with aging in the GK rat:a contrasted adaptation as compared with non-diabetic rat.Metabolism,1997,46(8):890-896.
[28]Turner N, Bruce CR, Beale SM.Excess Lipid Availability Increases Mitoch--ondrial Fatty Acid Oxidative Capacity in Muscle[J].DIABETES,2007,56(8): 2085-2092.
[29]Lauren M.Sparks,Hui Xie, Robert A.et al.A High-Fat Diet Coordinately Downregulates Genes Required for Mitochondrial Oxidative Phosphorylation in Skeletal Muscle [J].DIABETES,2005,54(7):1926-1933.
[30]赵婷婷,丁树哲,大鼠游泳运动后骨骼肌PGC-1αmRNA表达的时相性变化[J],上海体育学院学报,第30卷第3期,2006年5月,41-44.
[31]Baar,et al.Adaptations of Skeletal Muscle to Exercise:Rapid Increase in the Transcriptional Coactivator PGC-1[J].FASEB J,2002,16(14):1879-1886.
[32]Wright,D.C.,Han,D.H.,Garcia-Roves,P.M.,Geiger,P.C.,Jones,T.E.,andHolloszy,J. O.2007.Exercise-inducedmitochondrial Biogenesis begins before the increase in muscle PGC-1a expression.J.Biol.Chem.282:194-199.
[33]CarleyR.Benton,DavidC.Wright,and Arend Bonen.PGC-la-mediated regulation of gene expression and metabolism:implications for nutrition and exercise prescriptions.[J] Appl.Physiol.Nutr.Metab.2008.33:843-862
[34]张燕,王强,王东进.能量代谢与疾病的关键调控因子PGC-1α(上)[J].中国糖尿病杂志,2008,16(7)：385-388.
[35]Carley R.Benton, David C.Wright PGC-la-mediated regulation of gene expression And metabolism:implications for nutrition and exercise prescriptions. Appl.Physiol.Nutr.Metab.33:843-862(2008
[36]S.Ikeda,H.Kawamoto.Muscle type-specific responseofPGC-la and oxidative Enzymes during voluntary wheel running in mouse skeletal muscle.ActaPhysiol2006, 188,217-223
[37]Lehman,J.J.,Barger,P.M.,Kovacs,A.,Saffitz,J.E.,Medeiros,D.M.,andKelly,D.P.200 O.Peroxisomeproliferator-activated receptor g coactivator-1 promotes cardiac mitochondrial biogenesis.J.Clin.Invest.106:847-856
[38]Choi,C.S.,Rezneck,R.M.,Liu,Z.-X.,Kim,S.,Distefano,A.Samuel,V.T.,etal.2007.Di et induced insulin resistance is Paradoxically increased in transgenic mice with muscle-specific over expression of PGC-1a.Keystone Symp.Diabetes Mol.Genet. Signal.Pathways Integr.Physiol.115:157.
[39]Miura,S.,Kai,Y.,Ono,M.,andEzaki,O.2003.Over-expression of Peroxisomep roliferator-activated receptor g coactivator-1α down-Regulates GLUT4 mRNA in skeletal muscles.J.Biol.Chem.278:31385-31390.
[40]Miura,S.,Tomitsuka,E.,Kamei,Y.,Yamazaki,T.,Kai,Y.,Tamura,M.,etal.2006.Over expression of peroxisome proliferator-activated receptor g co-activator-1a leads to muscle atrophy with depletion of ATP.Am.J.Pathol.169:1129-1139.
[2]KingH, Aubert R E, Herman WH, et al.Global burden of diabetes. 1995-2025,prevalence numerical estmiates and projections [J].Diabetes Care,1998,21(9):1414-1431.
[3]文立,马国栋.运动与骨骼肌线粒体生物发生[J].中国运动医学杂志,2005,24(4)：484-488.
[4]Michael, Gaster. Insulin resistance and the mitochondrial link. Lessons from cultured human myotubes [J].Biochimica et Biophysica Acta,2007,1772(7): 755-765
[5]Hojlund K, Wrzesinski K, Larsen PM, et al.Proteome analysis reveals phosphorylation of ATP synthase beta-subunit in human skeletal muscle and proteins with potential roles in type 2 diabetes.J Biol Chem 2003; 278 (12):10436-42
[6]Morino K, Petersen KF, Dufour S,et al.Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents.J Clin Invest 2005; 115 (12):3587-93
[7]Petersen KF, Dufour S,Befroy D, et al.Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes.N Engl J Med 2004; 350 (7):664-71
[8]Befroy DE, Petersen KF, Dufour S,et al.Impaired mitochondrial substrate oxidation in muscle of insulin-resistant offspring of type 2 diabetic patients.Diabetes 2007; 56 (5):1376-81
[9]张燕,王强,王东进.能量代谢与疾病的关键调控因子PGC-1α(下)[J].中国糖尿病杂志,2008,16(8)：453-458.
[10]路中PGC-1α与糖尿病血糖代谢[J].国外医学老年医学分册,2003,24(3)：106-108.
[11]Patti ME, Butte AJ,Crunkhorn S,et al.coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes:Potential role of PGC-1 and NRF-1[J].Proc Natl Acad Sci USA,2003,100:8466-8471.
[12]Keith Baar. Involvement of PPAR Y co-activator-1,nuclear respiratory factors 1 and 2,and PPAR Y in the adaptive response to endurance exercise[J].Proceedings of the Nutrition Society,2004(63):269-273.
[13]王芬,何华亮,刘铜华.自发的2型糖尿病动物模型[J].中国实验动物学报,2007,15(5)：395-398.
[14]Goto Y,Kakizaki M.The spontaneous—diabetes rat:a model of non-insulin-dependent diabetes mellitus.Proc Jpn Aead,1981,57:381-384.
[15]Guru Y,Suzuki K,Sasaki M,Ono T,et al.GK rat as a mode 1 of non-obese, non-insulin—dependent diabetes:selective breeding over 35 generations.In Shafrir E,Renold AE (Eds).Frontiers in Diabetes Research.Lessons from Animal Diabetes Ⅱ.London:Libbey 1988,301-303.
[16]Bisbis S,Bailbe D,Tormo MA,et al.Insulin resistance in the GK rat: decreased receptor number but normal kinase activity in the liver.Am J Physiol, 1993.265:807-813.
[17]Ostenson CG,Khan A,Abdel—Halim SM.et al,Abnormal insulin secretion aim glucose metabolism in pancreatic islets from the spontaneously diabetic GK rat.Diabetologia,1993,36:3-8.
[18]Movassat J,Shinier C,Serradas P,et al.Impaired development of pancreatic beta—cell mass is a primary event during the progression to diabetes in the GK rat.Diabetologia,1997,40(8):916-925.
[19]Berthelier C,Kergoat M,Portha B.Lack of deterioration of insulin action with aging in the GK rat:a contrasted adaptation as compared with non-diabetic rat.Metabolism,1997,46(8):890—896.
[20]Gill—Randall RI,ADAMS D,Ollerton RL,et al.Is human type 2 diabetes masternally inherited?Insights from an animal model[J].Diabetic Medicine,2004, 21:759—762.
[21]徐倍,吴国亭等.2型糖尿病GK大鼠病程进展与组织形态学改变[J].同济大学学报(医学版),2007,28(5)：17-21.
[22]张丽萍,荣海钦,季虹等。2型糖尿病模型G K大鼠骨形态学和生物力学特点观察[J].中国实验动物学报,2008,16(5)：361-365.
[23]Spiegelman BM, and Heinrich R.Biological control through regulated transcriptional coactivators.Cell,2004,119:157-167.
[24]张燕,王强,王东进.能量代谢与疾病的关键调控因子PGC-1a(上)[J].中国糖尿病杂志,2008,16(7)：385-388.
[25]Puigserver P, Wu Z, Spiegelman BM, et al.A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis [J].Cell,1998,9:829-839.
[26]Lin J,Puigserver P, Donovan J, et al.Peroxisome proliferator-activated receptor γ coactivator 1β(PGC-1β), a novel PGC-1-related transcription coactivator associated with host cell factor. J Biol Chem,2002,277:1645-1648.
[27]Kressler D,Schreiber SN, Knutti D, et al.The PGC-1-related protein PERC is a selective coactivator of estrogen receptor a. J Biol Chem,2002,277:13918-13925.
[28]Andersson U, Scarpulla RC.Pgc-1-related coactivator, a novel,serum-inducible coactivator of nuclear respiratory factor 1-dependent transcription in mammalian cells. Mol Cell Biol,2001,21:3738-3749.
[29]Knutti D, Kaul A, Kralli A. A tissue-specific coactivator of steroid receptors, identified in a functional genetic screen.Mol Cell Biol,2000,20:2411-242
[30]Wallberg AE, Yamamura S,Malik S,et al.Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through coactivator PGC-1alpha. Mol Cell,2003,12:1137-114
[31]Leone TC, Lehman JJ,Finck BN, et al.PGC-lalpha deficiency causes multisystem energy metabolic derangements:muscle dysfunction, abnormal weight control and hepatic steatosis.PLoS Biol,2005,3:e101.
[32]Lin J,Yang R,Tarr PT, et al.Hyperlipidemic effects of dietary saturated fats mediated through PGC-lbeta coactivation of SREBP. Cell,2005,120:261-273.
[33]Lin J,Handschin C, Spiegelman BM. Metabolic control through the PGC-1 family transcription coactivators.Cell Metab,2005,1:361-370.
[34]Kawakami Y, Tsuda M,Takahashi S,et al.Transcriptional coactivator PGC-1{alpha} regulates chondrogenesis via association with Sox9·Proc Natl Acad Sci USA,2005,102:2414-2419.
[35]Brian N.Daniel P. Kelly. PGC-1 coactivators:inducible regulators of energy metabolism in health and disease [J].The Journal of Clinical Investigation. 2006.116(3):615-622.
[36]Lin J,Handschin C, Spiegelman BM.Metabolic control through the PGC-1 family transcription coactivators.Cell Metab,2005,1:361-370.
[37]Tiraby C,Tavernier G, Lefort C, et al.Acquirement of brown fat cell features by human white adipocytes.J Biol Chem,2003,278:33370-33376
[38]Michael LF, Wu Z,Cheatham RB,et al.Restoration of insulin-sensitive glucose transporter (GLUT4) gene expression in muscle cells bythe transcriptional coactivator PGC-1·Proc Natl Acad Sci USA,2001,98:3820-3825.
[39]Lehman JJ, Barger PM, Kovacs A, et al.Peroxisome proliferator-activated recep tor gamma coactivator-1 promotes cardiac mitochondrial biogenesis[J].J Clin Invest, 2000,106 (7):847-856.
[40]Bernal-Mizrachi C, Weng S,Feng C,et al.Dexamethasone induction of hypertension and diabetes is PPAR-a dependent in LDL receptor-null mice.Nat Med, 2003,9:1069-1075.
[41]Koo SH, Satoh H, Herzig S,et al.PGC-1 promotes insulin resistance in liver through PPARa-dependent induction of TRB-3-Nat Med,2004,10:530-534.
[42]Handschin C, Lin J, Rhee J,et al.Nutritional regulation of hepatic heme biosynthesis and porphyria through PGC-la. Cell,2005,122:505-515.
[43]Zurlo F, Larson K, Bogardus C,et al.Skeletal muscle metabolism is a major determinant of resting energy expenditure.J Clin Invest,1990,86:1423-1427.
[44]Zurlo F,Nemeth PM,Choksi RM,et al.Whole-body energy metabolism and skeletal muscle biochemical characteristics.Metabolism,1994,43:481-486.
[45]Lin J,Wu H, Tarr PT, et al.Transcriptional coactivator PGC-1α drives the for mation of slow-twitch muscle fibres [J].Nature,2002,418 (6899):797-801.
[46]路文盛,颜晓东,黄勤等PGC-1α基因MEF2C结构域482G/A变异参与2型糖尿病发病的机制研究[J].中华医学遗传学杂志,2008.25(6)：
[47]Wu Z, Puigserver P, AnderssonU,et al.Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1.Cell,1999,98: 115-124.
[48]Montoya J,Perez-Martos A and Garstka HL. Regulation ofmitochondrial transcription by mitochondrial transcription factor A. Mol Cell Biochem,1997,174: 227-230.
[49]Mao S,Leone TC,Kelly DP,et al.Mitochondrial transcription factor A is increased but expression of ATP synthase bet subunit and medium-chain acyl-CoA dehydrogenase gene are decreased in hearts of copper-deficient rats[J].J Nutr,2000,130:2143-2150.
[50]赵玉琼,陈华PGC-1基因与Ⅱ型糖尿病[J].实验动物科学,2008,25(6)：45-47.
[51]Yamamoto T, ShimanoH, Nakagawa Y,et al.SREBP-1 interacts with hepatocyte nuclear factor-4 alpha and interferes with PGC-1 recruitment to suppress hepatic gluconeogenic genes.J Biol Chem,2004,279:12027-12035.
[52]Yoon JC, Puigserver P, Chen G, et al.Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1·Nature,2001,413:131-138.
[53]Lowell BB,Shulman GI. Mitochondrial dysfunction and type 2 diabetes[J]. Science,2005,307:3842387.
[54]Kelley DE, He J,Menshikova EV,et al.Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes[J].Diabetes,2002,51:2944-2950.
[55]Giguere V, Yang N, Segui P, et al.Identification of a new class of steroid hormone receptors.Nature,1988,331(6151):91-94.
[56]Hong H, Yang L, Stallcup M R.Hormone-independent transcriptional activation and coactivator binding by novel orphan nuclear receptor ERRa.J Biol Chem,1999, 274(32):22618-22626.
[57]钱云霞,钱凯.先雌激素相关受ERR的功能及其调控.生物化学与生物物理进展,2005,32(6)：495-500.
[58]Sladek R,Beatty B,Squire J.Chromosomal mapping of the human and murine orphan receptors ERRa(ESRRA) and ERRβ(ESRRB) and identification of a novel human ERRa-related pseudogene.Genomics,1997,45(2):320～326.
[59]Feng W,Ribeiro,RC,Wagner R L,et al.Hormone-dependent coactivator binding to a hydrophobic cleft on nuclear receptors.Science,1998,280(5370): 1747-1749.
[60]Horard B,Vanacker J M. Estrogen receptor-related receptors:orphan receptors desperately seeking a ligand.J Mol Endocrinol,2003,31(3):349-357.
[61]Johnston S D,Liu X,Zuo F,et al.Estrogen—related receptor alfunctionally binds as a monomer to extended half-site sequences including ones contained、vithill estrogen—response elements.Mol Endocrinol,1997,11(3):342-352.
[62]赵丕文,牛建昭等.雌激素相关受体及其在雌激素信号转导体系中的作用.生命的化学,2008,28(5)：579-582.
[63]Hentschke M, Susens U,Borgmeyer U.PGC-1 and PERC,coactivators of the estrogen-receptor—related receptor.Biochem Biophys Res Commun,2002,299(5): 872～879.
[64]Heard DJ, Peder L. Norby, Jim Holloway, et al.Human ERRy, a Third Member of the Estrogen Receptor-Related Receptor (ERR) Subfamily of Orphan Nuclear Receptors:Tissue-Specific Isoforms Are Expressed during Development and in the Adult._Mol Endocrinol,2000,14(3):382-392
[65]Stein RA, McDonnell.Estrogen-related receptor aas a therapeutic target in cancer.Endocr Relat Cancer,2006,13(1):S25-S32
[66]Huss J M,Kopp RP,Kelly DP.PGC-la coactivates the cardiac—enriched nuclear receptor ERRα and γ via novel leucine-rich interaction interfaces.J Biol Chem,2002,277(43):40265-40274.
[67]Bonnelye E, Kung V, Laplace C, et al.Estrogen receptor-related receptor alpha impinges on the estrogen axis in bone:potential function in osteoporosis. Endocrinology,2002,143(9):3658-3670.
[68]Bonnelye E, Merdad L, Kung V, et al.The orphan nuclear estrogen receptor-related receptor a is expressed throughout osteoblast differentiation and regulates bone formation in vitro.J Cell Biol,2001,153(5):971-984.
[69]Kraus RJ, Ariazi EA, Farrell ML, et al.Estrogen-related receptor alpha 1 actively antagonizes estrogen receptor-regulated transcription in MCF-7 mammary cells.J Biol Chem,2002,277(27):24826-24834.
[70]Suzuki T, Miki Y, Moriya T, Shimada et al.Estrogen-related receptor alpha in human breast carcinoma as a potent prognostic factor. Cancer Research.2004(64):4670-4676
[71]Schreiber S N, Knutti D, Brogli K et al.The transcriptional coactivator PGC—1 regulates the expression and activity of the orphan nuclear receptor ERRa.J Biol Chem,2003,278(11):9013-9018.
[72]Carrier J C,Deblois G,Champigny C,et al.Estrogen related receptor a.is a transcriptional regulator of apolipoprotein A-IV and controls lipid handling in the intestine.J Biol Chem,2004,279(50):52052～52058.
[73]Adam R,Janice M, Paul J,et al.PGC-la Coactivates PDK4 Gene Expression via the Orphan Nuclear Receptor ERRa:a Mechanism for Transcriptional Control of Muscle Glucose Metabolism.Mol.Cell Biol,2005,25(24):10684-10694.
[74]Sylvia N, Roger Emter, Benjamin H,et al.The estrogen-related receptor a (ERRa)functions in PPARγ coactivator 1α (PGC-1α)-induced mitochondrial biogenesis.PNAS,2004,101(17):6472-6477.
[75]陈锐.核呼吸因子研究进展[J].国外医学·生理、病理科学与临床分册,2005,25(1)：59-61.
[76]Scarpulla RC. Nuclear activators and coactivators in mammalian mitochondrial biogenesis[J].Biochim BiophysActa,2002,1576(1-2):1-14.
[77]C. S.Kraft, C. M. R.LeMoine, C. N. Lyons, et al.Control of mitochondrial biogenesis during myogenesis [J].Am J Physiol Cell Physiol,2006; 290(4):C1119-C1127.
[78]江海洪.细胞核对线粒体呼吸链功能调控的研究[J].国外医学·生理、病理科学与临床分册,2001,21(3)：167-169.
[79]Davies KJ,PackerL and Brooks GA. Biochemical adaptation of mitochondria, muscle, and whole-animal respiration to endurance training[J].Arch Biochem Biophys,1981,209:539-554.
[80]赵婷婷,丁树哲,大鼠游泳运动后骨骼肌PGC-1 a mRNA表达的时相性变化[J],上海体育学院学报,第30卷第3期,2006年5月,4144.
[81]Akimoto T,Steven C,Pohnert,et al.Exercise Stimulates Pge-1 Transcription in.Skeletal Muscle through Activation of the p38 MAPK Pathway[J].Biol Chem, 2005,280:19587-19593.
[82]Goto M, Terada S,Kato M, et al.cDNA Cloning and mRNA analysis of PGC-1 in epitrochlearis muscle in swimming-exercised rats.Biochem Biophys Res Commun 2000; 274 (2):350-4
[83]Bengtsson J, Gustafsson T, Widegren U,et al.Mitochondrial transcription factor A and respiratory complex IV increase in response to exercise training in humans. Pflugers Arch 2001; 443(1):61-6
[84]62.Gordon JW, Rungi AA, Inagaki H, et al.Effects of contractile activity on mitochondrial transcription factor A expression in skeletal muscle.J Appl Physiol 2001; 90 (1):389-96
[85]Baar K, Wende AR,Jones TE, et al.Adaptations of skeletal muscle to exercise: rapid increase in the transcriptional coactivator PGC-1.Faseb J 2002; 16 (14): 1879-86
[86]Pilegaard H, Saltin B,Neufer PD.Exercise induces transient transcriptional activation of the PGC-lalpha gene in human skeletal muscle.J Physiol 2003;546 (Pt 3):851-8
[87]Cartoni R, Leger B, Hock MB,et al.Mitofusins 1/2 and ER-Ralpha expression are increased in human skeletal muscle after physical exercise. J Physiol 2005;567 (Pt 1):349-58
[88].Garnier A, Fortin D, Zoll J, et al.Coordinated changes in mitochondrial function and biogenesis in healthy and diseased human skeletal muscle.Faseb J 2005; 19 (1): 43-52
[89]Mahoney DJ,Parise G,Melov S,et al.Analysis of global mRNA expression in human skeletal muscle during recovery from endurance exercise.Faseb J 2005; 19 (11):1498-500
[90]Russell AP, Hesselink MK, Lo SK, et al.Regulation of metabolic transcriptional co-activators and transcription factors with acute exercise.Faseb J 2005;19 (8):986-8
[91]Terada S,Kawanaka K, Goto M, et al.Effects of high-intensity intermittent swimming on PGC-1alpha protein expression in rat skeletal muscle.Acta Physiol Scand 2005; 184 (1):59-65
[92]Adhihetty PJ,Taivassalo T, Haller RG,et al.The effect of training on the expression of mitochondrial biogenesis-and apoptosis-related proteins in skeletal muscle of patients with mtDNA defects.Am J Physiol Endocrinol Metab 2007; 293 (3):E672-80
[93]Wright DC, Han DH, Garcia-Roves PM, et al.Exercise-induced mitochondrial biogenesis begins before the increase in muscle PGC-1alpha expression. J Biol Chem 2007; 282 (1):194-9
[94]Jose A Lumini, Jose Magalhaes, Paulo J,et al.Beneficial Effects of Exercise on Muscle Mitochondrial Function in Diabetes Mellitus.[J] Sports Med 2008; 38 (9): 735-750.
[95]Wu H, Kanatous SB,Thurmond FA,et al.Regulation of mitochondrial biogenesis in skeletal muscle by CaMK[J].Science,2002,296:349-352.
[96]Handschin C,Rhee J,Lin J,et al.An auto-regulatory loop controls peroxisome proliferator-activated receptor gamma coactivator 1alpha expression in muscle.[J] Proc Natl Acad Sci USA,2003,100:7111-711
[97]Zong H, Ren JM,Y oung LH, et al.AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation[J].Proc Natl Acad Sci USA,2002,99:15983-15987.
[1]百度百科-糖尿病http://baike.baidu.com/view/923.htm.
[2]Hevener AL, Reichart D,Olefsky J,et al.Thiazolidinedione treatment prevents free fatty acid-induced insulin resistance in male wister rats[J].Diabetes,2001,50(10): 2316-2322.
[3]文立,马国栋.运动与骨骼肌线粒体生物发生[J].中国运动医学杂志,2005,24(4)：484-488.
[4]Morino K, Petersen KF, Dufour S,et al.Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents.J Clin Invest 2005; 115 (12):3587-93
[5]Petersen KF, Dufour S,Befroy D, et al.Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes.N Engl J Med 2004; 350 (7):664-71
[6]Befroy DE, Petersen KF, Dufour S,et al.Impaired mitochondrial substrate oxidation in muscle of insulin-resistant offspring of type 2 diabetic patients.Diabetes 2007; 56 (5):1376-81
[7]张燕,王强,王东进.能量代谢与疾病的关键调控因子PGC-1α(下)[J].中国糖尿病杂志,2008,16(8)：453-458.
[8]路中.PGC-1α与糖尿病血糖代谢[J].国外医学老年医学分册,2003,24(3)：106-108.
[9]Brian N. Daniel P.Kelly. PGC-1 coactivators:inducible regulators of energy metabolism in health and disease[J].The Journal of Clinical Investigation.2006.116(3):615-622.
[10]Sylvia N, Roger Emter, Benjamin H, et al.The estrogen-related receptor a (ERRa) functions in PPARy coactivator 1α(PGC-1α)-induced mitochondrial biogenesis. PNAS,2004,101(17):6472-6477.
[11]陈锐.核呼吸因子研究进展[J].国外医学·生理、病理科学与临床分册,2005,25(1)：59-61.
[12]Davies KJ, PackerL and Brooks GA. Biochemical adaptation of mitochondria, muscle, and whole-animal respiration to endurance training[J].Arch Biochem Biophys,1981,209:539-554.
[13]Jose A Lumini,Jose Magalhaes, Paulo J, et al.Beneficial Effects of Exercise on Muscle Mitochondrial Function in Diabetes Mellitus.[J] Sports Med 2008; 38 (9): 735-750.
[14]Schrauwen P,Westerterp KR.The role of high-fat diets and physical activity in the regulation of body weight[J].British Journal of Nutrition,2000,84(4):417-427.
[15]李翠珍,赵刚.耐力训练对雄性高脂膳食大鼠脂代谢异常及胰岛素水平的影响.辽宁大学学报.自然科学版.2008.35(4)：363-366
[16]百度百科-胰岛素http://baike.baidu.com/view/1340.htm.
[17]许斯华,金文胜,林延.2型糖尿病血糖与胰岛素释放关系的探讨第一军医大学学报2003；23(8)：859-862.
[18]维基百科-胰岛素抵抗http://zh.wikipedia.org/wiki/胰岛素抵抗.
[19]默里 RK,格兰纳DK,迈耶斯PA等,宋惠萍等译.哈珀生物化学(第25版)[M].科学出版社,2003.
[20]Silva da RC，Miranda WL,Chacra AR,et al.Insulin resistance,beta-cellfunction, and glucose tolerance in Brazilian adolescents with obesity or risk factors for type 2 diabetes mellitus[J].Journal of Diabetes and its Complications,2007,21(2):84-92.
[21]Litherland GJ,Morris NJ,Walker M, et al.Role of glycogen content in insulin resistance in human muscle cells[J].Cell Physiol,2007,211(2):344-352.
[22]Joris Hoeks, Jacob J.Briede, Johan de Vogel.Mitochondrial function, content and ROS production in rat skeletal muscle:Effect of high-fat feeding[J].FEBS Letters,2008,582(5):510-516.
[23]Unger R H.Lipotoxicity of cells in obesity and in other causes of fatty acid spillover [J]. Diabetes,2001,50(Suppll):518-521.
[24]S.Iwashita, MamoruTanida et.al.Decreased skeletal muscle insulin receptors in high-fat diet-related hypertensive rats.1./NutritionResearch22(2002)1049-1053
[25]胰岛素受体学说与Ⅱ型糖尿病胰岛素抵抗http://age.bjmu.cn/old/progress/pbl/07.pdf
[26]陈丹,毕会民,毕欣,运动对胰岛素抵抗大鼠骨骼集中糖原合成酶激酶-3表达的影响[J].中华物理医学与康复杂志,2006,28(3)：153—156.
[27]Berthelier C,Kergoat M,Portha B.Lack of deterioration of insulin action with aging in the GK rat:a contrasted adaptation as compared with non-diabetic rat.Metabolism,1997,46(8):890-896.
[28]Turner N, Bruce CR, Beale SM.Excess Lipid Availability Increases Mitoch--ondrial Fatty Acid Oxidative Capacity in Muscle[J].DIABETES,2007,56(8): 2085-2092.
[29]Lauren M.Sparks,Hui Xie, Robert A.et al.A High-Fat Diet Coordinately Downregulates Genes Required for Mitochondrial Oxidative Phosphorylation in Skeletal Muscle [J].DIABETES,2005,54(7):1926-1933.
[30]赵婷婷,丁树哲,大鼠游泳运动后骨骼肌PGC-1αmRNA表达的时相性变化[J],上海体育学院学报,第30卷第3期,2006年5月,41-44.
[31]Baar,et al.Adaptations of Skeletal Muscle to Exercise:Rapid Increase in the Transcriptional Coactivator PGC-1[J].FASEB J,2002,16(14):1879-1886.
[32]Wright,D.C.,Han,D.H.,Garcia-Roves,P.M.,Geiger,P.C.,Jones,T.E.,andHolloszy,J. O.2007.Exercise-inducedmitochondrial Biogenesis begins before the increase in muscle PGC-1a expression.J.Biol.Chem.282:194-199.
[33]CarleyR.Benton,DavidC.Wright,and Arend Bonen.PGC-la-mediated regulation of gene expression and metabolism:implications for nutrition and exercise prescriptions.[J] Appl.Physiol.Nutr.Metab.2008.33:843-862
[34]张燕,王强,王东进.能量代谢与疾病的关键调控因子PGC-1α(上)[J].中国糖尿病杂志,2008,16(7)：385-388.
[35]Carley R.Benton, David C.Wright PGC-la-mediated regulation of gene expression And metabolism:implications for nutrition and exercise prescriptions. Appl.Physiol.Nutr.Metab.33:843-862(2008
[36]S.Ikeda,H.Kawamoto.Muscle type-specific responseofPGC-la and oxidative Enzymes during voluntary wheel running in mouse skeletal muscle.ActaPhysiol2006, 188,217-223
[37]Lehman,J.J.,Barger,P.M.,Kovacs,A.,Saffitz,J.E.,Medeiros,D.M.,andKelly,D.P.200 O.Peroxisomeproliferator-activated receptor g coactivator-1 promotes cardiac mitochondrial biogenesis.J.Clin.Invest.106:847-856
[38]Choi,C.S.,Rezneck,R.M.,Liu,Z.-X.,Kim,S.,Distefano,A.Samuel,V.T.,etal.2007.Di et induced insulin resistance is Paradoxically increased in transgenic mice with muscle-specific over expression of PGC-1a.Keystone Symp.Diabetes Mol.Genet. Signal.Pathways Integr.Physiol.115:157.
[39]Miura,S.,Kai,Y.,Ono,M.,andEzaki,O.2003.Over-expression of Peroxisomep roliferator-activated receptor g coactivator-1α down-Regulates GLUT4 mRNA in skeletal muscles.J.Biol.Chem.278:31385-31390.
[40]Miura,S.,Tomitsuka,E.,Kamei,Y.,Yamazaki,T.,Kai,Y.,Tamura,M.,etal.2006.Over expression of peroxisome proliferator-activated receptor g co-activator-1a leads to muscle atrophy with depletion of ATP.Am.J.Pathol.169:1129-1139.