跳到主要內容

臺灣博碩士論文加值系統

(44.211.117.197) 您好!臺灣時間:2024/05/22 01:04
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:洪振庭
研究生(外文):Chen-Ting Hung
論文名稱:KMUP-3防止高糖引起之心肌細胞傷害及改善糖尿病大鼠之心臟功能
論文名稱(外文):KMUP-3 Prevents High Glucose-Induced Cardiomyocytes Injury and Improves Cardiac Functions in Diabetes Rats
指導教授:葉竹來葉竹來引用關係
指導教授(外文):Jwu-Lai Yeh
學位類別:碩士
校院名稱:高雄醫學大學
系所名稱:醫學系藥理學科碩士班
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2015
畢業學年度:103
語文別:中文
論文頁數:84
中文關鍵詞:細胞自噬糖尿病大鼠
外文關鍵詞:AutophagyDiabetes mellitus rats
相關次數:
  • 被引用被引用:0
  • 點閱點閱:176
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
糖尿病心肌病變,常見的併發症有高血壓、高血糖和心室肥厚,這些併發症皆是導致心臟衰竭的主要原因。先前,已有研究報告指出,糖尿病會導致心肌細胞凋亡作用和抑制自噬作用,而細胞自噬和細胞凋亡作用之間的關係在糖尿病心肌病變的發病機制中扮演著重要角色。本實驗最近的研究指出,KMUP-3在心肌細胞中能誘導細胞自噬作用。因此,我們進一步研究KMUP-3是否能夠促使細胞自噬作用產生來預防高血糖引起之心肌損傷並且改善糖尿病大鼠心臟功能。在本篇研究中,取用初生鼠之心肌細胞來模仿高血糖狀態。將心肌細胞培養在葡萄糖濃度為30 mM的細胞培養液中再加入濃度為1到10 &;#61549;M的KMUP-3。糖尿病大鼠動物模式誘導方式為給予65mg/kg劑量的鏈&;#33074;佐菌素(Strptozotocin, STZ)進行誘導。KMUP-3則以腹腔注射方式給予1 mg/ kg的劑量。心臟功能評估是由小動物超音波儀器檢測。經由MTT試驗,發現KMUP-3治療能有效減少高糖誘導的心肌細胞死亡。另外,KMUP-3也可以抑制高糖誘導的心肌細胞凋亡,與促細胞存活蛋白Bcl-2的表現量增加,並且降低促細胞凋亡蛋白Bax與cleaved caspase-3的表現量有關。微管相關蛋白I輕鏈3-Ⅱ(LC3-II)是細胞自噬關鍵蛋白。 KMUP-3以時間依賴性明顯增強LC3-II的表現量和促使AMPK蛋白的磷酸化。正如預期,KMUP-3的前處理具劑量依賴性並增強高糖誘導的LC3-II、Atg7和磷酸化AMPK蛋白之表現量。在糖尿病大鼠動物模式中,其縮短分率(FS)、射血分率(EF)及左心室收縮功能的指數明顯下降。跟糖尿病組別相比較,給予KMUP-3的組別其心臟功能指數能有效改善。總而言之,KMUP-3透過誘導細胞自噬作用減少高糖誘導之心肌細胞的細胞凋亡。這些結果顯示,KMUP-3在糖尿病心肌病變的治療中具有巨大的潛力。

Diabetes cardiomyopathy, a common disease occurring hypertension, hyperglycemia and ventricle hypertrophy in diabetes patients, is a major complication leads to heart failure. Recently, studies have reported that diabetes induced cardiomyocyte apoptosis and suppressed cardiac autophagy, showing that the relationship between the autophagy and apoptotic cell death pathways plays an important role in the pathogenesis of diabetic cardiomyopathy. Our recent studies indicated that KMUP-3 can induce autophagy in cardiomyocytes. Therefore, we further investigated whether KMUP-3’s promotion of autophagy activity can prevent high glucose (HG)-induce cardiac injury and improve cardiac functions in diabetes mellitus (DM) rats.
In this study, we mimicked hyperglycemia condition in neonatal rat (1-3 day) cardiomyocytes with HG model. Cardiomyocytes were incubated in 30 mM HG in the presence or absence of KMUP-3 (1 to 10 &;#61549;M). An experimental diabetic rat model was induced by 65 mg/kg of streptozoticin (STZ). KMUP-3 was intraperitoneally injected at a dose of 1 mg/kg. Cardiac functions were evaluated by serial echocardiography. We found that KMUP-3 treatment attenuated HG-induced cell death by MTT assay. Additionally, KMUP-3 also inhibited HG-induced apoptosis, with associated increase of Bcl-2 protein, and decrease of Bax protein and caspase-3 cleavage. Microtubule-associated protein I light chain 3-II (LC3-II) is the key protein associated with autophagy. KMUP-3 significantly enhanced production of LC3-II and phosphorylation of AMPK in a time-dependent manner. As expected, KMUP-3 pretreatment dose-dependently reduced the HG-induced decrease of LC3-II, Atg7, and phosphor-AMPK expression. Fractional shortening (FS) and ejection fraction (EF), the index of left ventricular systolic function, were significantly decreased in DM group. Then compared with DM group, these changes were attenuated when diabetic rats were treated with KMUP-3 (P<0.05).
In summary, KMUP-3 attenuates HG-induced cardiomyocytes apoptosis by inducing autophagy. These findings suggest that KMUP-3 may have great therapeutic potential in the treatment of diabetic cardiomyopathy.


目次
中文摘要...................................1
英文摘要...................................3
縮寫表.....................................4
第一章 緒論................................6
第二章 研究目的............................21
第三章 研究材料............................22
第四章 研究方法............................28
第五章 研究結果............................35
第六章 討論................................41
第七章 未來展望............................49
參考文獻...................................50
附圖.......................................58


1.Su J, Zhou L, Kong X, Yang X, Xiang X, Zhang Y, et al. Endoplasmic reticulum is at the crossroads of autophagy, inflammation, and apoptosis signaling pathways and participates in the pathogenesis of diabetes mellitus. Journal of diabetes research. 2013;2013:193461.
2.Salminen A, Kaarniranta K, Kauppinen A. Beclin 1 interactome controls the crosstalk between apoptosis, autophagy and inflammasome activation: impact on the aging process. Ageing research reviews. 2013;12(2):520-34.
3.Zhou F, Yang Y, Xing D. Bcl-2 and Bcl-xL play important roles in the crosstalk between autophagy and apoptosis. The Federation of European Biochemical Societies journal. 2011;278(3):403-13.
4.Maiuri MC, Criollo A, Kroemer G. Crosstalk between apoptosis and autophagy within the Beclin 1 interactome. The EMBO journal. 2010;29(3):515-6.
5.Djavaheri-Mergny M, Maiuri MC, Kroemer G. Cross talk between apoptosis and autophagy by caspase-mediated cleavage of Beclin 1. Oncogene. 2010;29(12):1717-9.
6.Cassetti MC, Katz JM, Wood J. Report of a consultation on role of immunological assays to evaluate efficacy of influenza vaccines. Initiative for Vaccine Research and Global Influenza Programme, World Health Organization, Geneva, Switzerland, 25 January 2005. Vaccine. 2006;24(5):541-3.
7.Vijan S. Type 2 diabetes. Annals of internal medicine. 2010;152(5):ITC31-15; quiz ITC316.
8.Ripsin CM, Kang H, Urban RJ. Management of blood glucose in type 2 diabetes mellitus. American family physician. 2009;79(1):29-36.
9.Qaseem A, Humphrey LL, Sweet DE, Starkey M, Shekelle P, Clinical Guidelines Committee of the American College of P. Oral pharmacologic treatment of type 2 diabetes mellitus: a clinical practice guideline from the American College of Physicians. Annals of internal medicine. 2012;156(3):218-31.
10.American Diabetes A. Standards of medical care in diabetes--2012. Diabetes care. 2012;35 Suppl 1:S11-63.
11.Factor SM, Bhan R, Minase T, Wolinsky H, Sonnenblick EH. Hypertensive-diabetic cardiomyopathy in the rat: an experimental model of human disease. The American journal of pathology. 1981;102(2):219-28.
12.Aneja A, Tang WH, Bansilal S, Garcia MJ, Farkouh ME. Diabetic cardiomyopathy: insights into pathogenesis, diagnostic challenges, and therapeutic options. The American journal of medicine. 2008;121(9):748-57.
13.Rerkpattanapipat P, D''Agostino RB, Jr., Link KM, Shahar E, Lima JA, Bluemke DA, et al. Location of arterial stiffening differs in those with impaired fasting glucose versus diabetes: implications for left ventricular hypertrophy from the Multi-Ethnic Study of Atherosclerosis. Diabetes. 2009;58(4):946-53.
14.Eguchi K, Boden-Albala B, Jin Z, Rundek T, Sacco RL, Homma S, et al. Association between diabetes mellitus and left ventricular hypertrophy in a multiethnic population. The American journal of cardiology. 2008;101(12):1787-91.
15.Woodiwiss AJ, Libhaber CD, Majane OH, Libhaber E, Maseko M, Norton GR. Obesity promotes left ventricular concentric rather than eccentric geometric remodeling and hypertrophy independent of blood pressure. American journal of hypertension. 2008;21(10):1144-51.
16.Barouch LA, Berkowitz DE, Harrison RW, O''Donnell CP, Hare JM. Disruption of leptin signaling contributes to cardiac hypertrophy independently of body weight in mice. Circulation. 2003;108(6):754-9.
17.Xu FP, Chen MS, Wang YZ, Yi Q, Lin SB, Chen AF, et al. Leptin induces hypertrophy via endothelin-1-reactive oxygen species pathway in cultured neonatal rat cardiomyocytes. Circulation. 2004;110(10):1269-75.
18.Kim M, Oh JK, Sakata S, Liang I, Park W, Hajjar RJ, et al. Role of resistin in cardiac contractility and hypertrophy. Journal of molecular and cellular cardiology. 2008;45(2):270-80.
19.Bahrami H, Bluemke DA, Kronmal R, Bertoni AG, Lloyd-Jones DM, Shahar E, et al. Novel metabolic risk factors for incident heart failure and their relationship with obesity: the MESA (Multi-Ethnic Study of Atherosclerosis) study. Journal of the American College of Cardiology. 2008;51(18):1775-83.
20.Karason K, Sjostrom L, Wallentin I, Peltonen M. Impact of blood pressure and insulin on the relationship between body fat and left ventricular structure. European heart journal. 2003;24(16):1500-5.
21.Ingelsson E, Sundstrom J, Arnlov J, Zethelius B, Lind L. Insulin resistance and risk of congestive heart failure. Jama. 2005;294(3):334-41.
22.Cook SA, Varela-Carver A, Mongillo M, Kleinert C, Khan MT, Leccisotti L, et al. Abnormal myocardial insulin signalling in type 2 diabetes and left-ventricular dysfunction. European heart journal. 2010;31(1):100-11.
23.Belke DD, Betuing S, Tuttle MJ, Graveleau C, Young ME, Pham M, et al. Insulin signaling coordinately regulates cardiac size, metabolism, and contractile protein isoform expression. The Journal of clinical investigation. 2002;109(5):629-39.
24.Boudina S, Sena S, Theobald H, Sheng X, Wright JJ, Hu XX, et al. Mitochondrial energetics in the heart in obesity-related diabetes: direct evidence for increased uncoupled respiration and activation of uncoupling proteins. Diabetes. 2007;56(10):2457-66.
25.Bugger H, Boudina S, Hu XX, Tuinei J, Zaha VG, Theobald HA, et al. Type 1 diabetic akita mouse hearts are insulin sensitive but manifest structurally abnormal mitochondria that remain coupled despite increased uncoupling protein 3. Diabetes. 2008;57(11):2924-32.
26.Boudina S, Bugger H, Sena S, O''Neill BT, Zaha VG, Ilkun O, et al. Contribution of impaired myocardial insulin signaling to mitochondrial dysfunction and oxidative stress in the heart. Circulation. 2009;119(9):1272-83.
27.Li L, Renier G. Activation of nicotinamide adenine dinucleotide phosphate (reduced form) oxidase by advanced glycation end products links oxidative stress to altered retinal vascular endothelial growth factor expression. Metabolism: clinical and experimental. 2006;55(11):1516-23.
28.Serpillon S, Floyd BC, Gupte RS, George S, Kozicky M, Neito V, et al. Superoxide production by NAD(P)H oxidase and mitochondria is increased in genetically obese and hyperglycemic rat heart and aorta before the development of cardiac dysfunction. The role of glucose-6-phosphate dehydrogenase-derived NADPH. American journal of physiology Heart and circulatory physiology. 2009;297(1):H153-62.
29.Frustaci A, Kajstura J, Chimenti C, Jakoniuk I, Leri A, Maseri A, et al. Myocardial cell death in human diabetes. Circulation research. 2000;87(12):1123-32.
30.Aragno M, Mastrocola R, Medana C, Catalano MG, Vercellinatto I, Danni O, et al. Oxidative stress-dependent impairment of cardiac-specific transcription factors in experimental diabetes. Endocrinology. 2006;147(12):5967-74.
31.Shen E, Li Y, Li Y, Shan L, Zhu H, Feng Q, et al. Rac1 is required for cardiomyocyte apoptosis during hyperglycemia. Diabetes. 2009;58(10):2386-95.
32.Dhalla NS, Liu X, Panagia V, Takeda N. Subcellular remodeling and heart dysfunction in chronic diabetes. Cardiovascular research. 1998;40(2):239-47.
33.Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. The New England journal of medicine. 2001;345(12):861-9.
34.Symeonides P, Koulouris S, Vratsista E, Triantafyllou K, Ioannidis G, Thalassinos N, et al. Both ramipril and telmisartan reverse indices of early diabetic cardiomyopathy: a comparative study. European journal of echocardiography : the journal of the Working Group on Echocardiography of the European Society of Cardiology. 2007;8(6):480-6.
35.Tsutsui H, Matsushima S, Kinugawa S, Ide T, Inoue N, Ohta Y, et al. Angiotensin II type 1 receptor blocker attenuates myocardial remodeling and preserves diastolic function in diabetic heart. Hypertension research : official journal of the Japanese Society of Hypertension. 2007;30(5):439-49.
36.Boudina S, Sena S, O''Neill BT, Tathireddy P, Young ME, Abel ED. Reduced mitochondrial oxidative capacity and increased mitochondrial uncoupling impair myocardial energetics in obesity. Circulation. 2005;112(17):2686-95.
37.Wiederkehr A, Wollheim CB. Impact of mitochondrial calcium on the coupling of metabolism to insulin secretion in the pancreatic beta-cell. Cell calcium. 2008;44(1):64-76.
38.Lenzen S, Drinkgern J, Tiedge M. Low antioxidant enzyme gene expression in pancreatic islets compared with various other mouse tissues. Free radical biology &; medicine. 1996;20(3):463-6.
39.Sekine N, Cirulli V, Regazzi R, Brown LJ, Gine E, Tamarit-Rodriguez J, et al. Low lactate dehydrogenase and high mitochondrial glycerol phosphate dehydrogenase in pancreatic beta-cells. Potential role in nutrient sensing. The Journal of biological chemistry. 1994;269(7):4895-902.
40.Deter RL, De Duve C. Influence of glucagon, an inducer of cellular autophagy, on some physical properties of rat liver lysosomes. The Journal of cell biology. 1967;33(2):437-49.
41.Saftig P, Beertsen W, Eskelinen EL. LAMP-2: a control step for phagosome and autophagosome maturation. Autophagy. 2008;4(4):510-2.
42.Kostin S, Pool L, Elsasser A, Hein S, Drexler HC, Arnon E, et al. Myocytes die by multiple mechanisms in failing human hearts. Circulation research. 2003;92(7):715-24.
43.Akazawa H, Komazaki S, Shimomura H, Terasaki F, Zou Y, Takano H, et al. Diphtheria toxin-induced autophagic cardiomyocyte death plays a pathogenic role in mouse model of heart failure. The Journal of biological chemistry. 2004;279(39):41095-103.
44.Gustafsson AB, Gottlieb RA. Autophagy in ischemic heart disease. Circulation research. 2009;104(2):150-8.
45.Nakai A, Yamaguchi O, Takeda T, Higuchi Y, Hikoso S, Taniike M, et al. The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress. Nature medicine. 2007;13(5):619-24.
46.Matsui Y, Takagi H, Qu X, Abdellatif M, Sakoda H, Asano T, et al. Distinct roles of autophagy in the heart during ischemia and reperfusion: roles of AMP-activated protein kinase and Beclin 1 in mediating autophagy. Circulation research. 2007;100(6):914-22.
47.Zhu H, Tannous P, Johnstone JL, Kong Y, Shelton JM, Richardson JA, et al. Cardiac autophagy is a maladaptive response to hemodynamic stress. The Journal of clinical investigation. 2007;117(7):1782-93.
48.Epstein PN, Overbeek PA, Means AR. Calmodulin-induced early-onset diabetes in transgenic mice. Cell. 1989;58(6):1067-73.
49.Xie Z, Lau K, Eby B, Lozano P, He C, Pennington B, et al. Improvement of cardiac functions by chronic metformin treatment is associated with enhanced cardiac autophagy in diabetic OVE26 mice. Diabetes. 2011;60(6):1770-8.
50.He C, Zhu H, Li H, Zou MH, Xie Z. Dissociation of Bcl-2-Beclin1 complex by activated AMPK enhances cardiac autophagy and protects against cardiomyocyte apoptosis in diabetes. Diabetes. 2013;62(4):1270-81.
51.Kobayashi S, Xu X, Chen K, Liang Q. Suppression of autophagy is protective in high glucose-induced cardiomyocyte injury. Autophagy. 2012;8(4):577-92.
52.Mellor KM, Reichelt ME, Delbridge LM. Autophagic predisposition in the insulin resistant diabetic heart. Life sciences. 2013;92(11):616-20.
53.Morales CR, Pedrozo Z, Lavandero S, Hill JA. Oxidative stress and autophagy in cardiovascular homeostasis. Antioxidants &; redox signaling. 2014;20(3):507-18.
54.Luo C, Li Y, Wang H, Feng Z, Li Y, Long J, et al. Mitochondrial accumulation under oxidative stress is due to defects in autophagy. Journal of cellular biochemistry. 2013;114(1):212-9.
55.Scherz-Shouval R, Shvets E, Elazar Z. Oxidation as a post-translational modification that regulates autophagy. Autophagy. 2007;3(4):371-3.
56.Oberstein A, Jeffrey PD, Shi Y. Crystal structure of the Bcl-XL-Beclin 1 peptide complex: Beclin 1 is a novel BH3-only protein. The Journal of biological chemistry. 2007;282(17):13123-32.
57.Levine B, Sinha S, Kroemer G. Bcl-2 family members: dual regulators of apoptosis and autophagy. Autophagy. 2008;4(5):600-6. PubMed PMID: 18497563;
58.Pattingre S, Tassa A, Qu X, Garuti R, Liang XH, Mizushima N, et al. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell. 2005;122(6):927-39.
59.Wei Y, Pattingre S, Sinha S, Bassik M, Levine B. JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy. Molecular cell. 2008;30(6):678-88.
60.Wirawan E, Vande Walle L, Kersse K, Cornelis S, Claerhout S, Vanoverberghe I, et al. Caspase-mediated cleavage of Beclin-1 inactivates Beclin-1-induced autophagy and enhances apoptosis by promoting the release of proapoptotic factors from mitochondria. Cell death &; disease. 2010;1:e18.
61.Yousefi S, Perozzo R, Schmid I, Ziemiecki A, Schaffner T, Scapozza L, et al. Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis. Nature cell biology. 2006;8(10):1124-32.
62.Betin VM, Lane JD. Atg4D at the interface between autophagy and apoptosis. Autophagy. 2009;5(7):1057-9.
63.Hardie DG. AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nature reviews Molecular cell biology. 2007;8(10):774-85.
64.Shirwany NA, Zou MH. AMPK in cardiovascular health and disease. Acta pharmacologica Sinica. 2010;31(9):1075-84.
65.Xie Z, Dong Y, Zhang M, Cui MZ, Cohen RA, Riek U, et al. Activation of protein kinase C zeta by peroxynitrite regulates LKB1-dependent AMP-activated protein kinase in cultured endothelial cells. The Journal of biological chemistry. 2006;281(10):6366-75.
66.Xie Z, Dong Y, Zhang J, Scholz R, Neumann D, Zou MH. Identification of the serine 307 of LKB1 as a novel phosphorylation site essential for its nucleocytoplasmic transport and endothelial cell angiogenesis. Molecular and cellular biology. 2009;29(13):3582-96.
67.Xie Z, Zhang J, Wu J, Viollet B, Zou MH. Upregulation of mitochondrial uncoupling protein-2 by the AMP-activated protein kinase in endothelial cells attenuates oxidative stress in diabetes. Diabetes. 2008;57(12):3222-30.
68.Xie Z, Dong Y, Scholz R, Neumann D, Zou MH. Phosphorylation of LKB1 at serine 428 by protein kinase C-zeta is required for metformin-enhanced activation of the AMP-activated protein kinase in endothelial cells. Circulation. 2008;117(7):952-62.
69.Shaw RJ. LKB1 and AMP-activated protein kinase control of mTOR signalling and growth. Acta physiologica. 2009;196(1):65-80.
70.Kim J, Kundu M, Viollet B, Guan KL. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nature cell biology. 2011;13(2):132-41.
71.Egan DF, Shackelford DB, Mihaylova MM, Gelino S, Kohnz RA, Mair W, et al. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science. 2011;331(6016):456-61.
72.Shang L, Chen S, Du F, Li S, Zhao L, Wang X. Nutrient starvation elicits an acute autophagic response mediated by Ulk1 dephosphorylation and its subsequent dissociation from AMPK. Proceedings of the National Academy of Sciences of the United States of America. 2011;108(12):4788-93.
73.Kim J, Kim YC, Fang C, Russell RC, Kim JH, Fan W, et al. Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagy. Cell. 2013;152(1-2):290-303.
74.Wu BN, Chen IC, Lin RJ, Chiu CC, An LM, Chen IJ. Aortic smooth muscle relaxants KMUP-3 and KMUP-4, two nitrophenylpiperazine derivatives of xanthine, display cGMP-enhancing activity: roles of endothelium, phosphodiesterase, and K+ channel. Journal of cardiovascular pharmacology. 2005;46(5):600-8.
75.Liu CP, Yeh JL, Wu BN, Chai CY, Chen IJ, Lai WT. KMUP-3 attenuates ventricular remodelling after myocardial infarction through eNOS enhancement and restoration of MMP-9/TIMP-1 balance. British journal of pharmacology. 2011;162(1):126-35.
76.Lai EH, Hong CY, Kok SH, Hou KL, Chao LH, Lin LD, et al. Simvastatin alleviates the progression of periapical lesions by modulating autophagy and apoptosis in osteoblasts. Journal of endodontics. 2012;38(6):757-63.
77.Nishida K, Yamaguchi O, Otsu K. Crosstalk between autophagy and apoptosis in heart disease. Circulation research. 2008;103(4):343-51.
78.Xie Z, He C, Zou MH. AMP-activated protein kinase modulates cardiac autophagy in diabetic cardiomyopathy. Autophagy. 2011;7(10):1254-5.
79.Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, et al. Role of AMP-activated protein kinase in mechanism of metformin action. The Journal of clinical investigation. 2001;108(8):1167-74.
80.Teng AC, Miyake T, Yokoe S, Zhang L, Rezende LM, Jr., Sharma P, et al. Metformin increases degradation of phospholamban via autophagy in cardiomyocytes. Proceedings of the National Academy of Sciences of the United States of America. 2015;112(23):7165-70.
81.Chen ZF, Li YB, Han JY, Yin JJ, Wang Y, Zhu LB, et al. Liraglutide prevents high glucose level induced insulinoma cells apoptosis by targeting autophagy. Chinese medical journal. 2013;126(5):937-41.
82.Li HL, Yin R, Chen D, Liu D, Wang D, Yang Q, et al. Long-term activation of adenosine monophosphate-activated protein kinase attenuates pressure-overload-induced cardiac hypertrophy. Journal of cellular biochemistry. 2007;100(5):1086-99.
83.Ibdah JA, Paul H, Zhao Y, Binford S, Salleng K, Cline M, et al. Lack of mitochondrial trifunctional protein in mice causes neonatal hypoglycemia and sudden death. The Journal of clinical investigation. 2001;107(11):1403-9.
84.Barger PM, Brandt JM, Leone TC, Weinheimer CJ, Kelly DP. Deactivation of peroxisome proliferator-activated receptor-alpha during cardiac hypertrophic growth. The Journal of clinical investigation. 2000;105(12):1723-30.
85.Goikoetxea MJ, Beaumont J, Gonzalez A, Lopez B, Querejeta R, Larman M, et al. Altered cardiac expression of peroxisome proliferator-activated receptor-isoforms in patients with hypertensive heart disease. Cardiovascular research. 2006;69(4):899-907.
86.Meng RS, Pei ZH, Yin R, Zhang CX, Chen BL, Zhang Y, et al. Adenosine monophosphate-activated protein kinase inhibits cardiac hypertrophy through reactivating peroxisome proliferator-activated receptor-alpha signaling pathway. European journal of pharmacology. 2009;620(1-3):63-70.
87.Lin J, Handschin C, Spiegelman BM. Metabolic control through the PGC-1 family of transcription coactivators. Cell metabolism. 2005;1(6):361-70.
88.Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell. 1998;92(6):829-39.
89.Lehman JJ, Barger PM, Kovacs A, Saffitz JE, Medeiros DM, Kelly DP. Peroxisome proliferator-activated receptor gamma coactivator-1 promotes cardiac mitochondrial biogenesis. The Journal of clinical investigation. 2000;106(7):847-56.
90.Huss JM, Kopp RP, Kelly DP. Peroxisome proliferator-activated receptor coactivator-1alpha (PGC-1alpha) coactivates the cardiac-enriched nuclear receptors estrogen-related receptor-alpha and -gamma. Identification of novel leucine-rich interaction motif within PGC-1alpha. The Journal of biological chemistry. 2002;277(43):40265-74.
91.Huss JM, Kelly DP. Nuclear receptor signaling and cardiac energetics. Circulation research. 2004;95(6):568-78.
92.Terada S, Goto M, Kato M, Kawanaka K, Shimokawa T, Tabata I. Effects of low-intensity prolonged exercise on PGC-1 mRNA expression in rat epitrochlearis muscle. Biochemical and biophysical research communications. 2002;296(2):350-4.
93.Finck BN, Kelly DP. PGC-1 coactivators: inducible regulators of energy metabolism in health and disease. The Journal of clinical investigation. 2006;116(3):615-22.


QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關論文