二甲双胍和有氧运动对高脂诱导肥胖大鼠血清及不同组织Visfatin蛋白表达水平的影响
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摘要
背景代谢综合征发生、发展的中心环节是体内存在胰岛素抵抗,而中心性肥胖是导致胰岛素抵抗的主要原因。Visfatin(内脏脂肪素)是脂肪组织所产生的分泌性蛋白,主要由内脏脂肪组织分泌产生,在肝脏、胰腺、心脏、胎盘、肺、肾等许多组织也有表达。研究表明,Visfatin有类胰岛素样作用,对改善胰岛素敏感性非常重要。二甲双胍,有氧运动可以减轻体重,改善胰岛素敏感性,但目前国内外鲜有Visfatin与二者关系的报道。本研究通过高脂饮食诱导肥胖大鼠,观察二甲双胍、有氧运动干预后Visfatin的变化,并初步探讨其可能的机制。
目的观察二甲双胍,有氧运动分别及联合干预对高脂饲料诱导的肥胖大鼠血清、附睾脂肪、皮下脂肪、肝脏组织Visfatin及相关代谢指标的影响。
方法将70只雄性6周龄Sprague-Dawley(SD)大鼠随机分为普通饮食组(ND, n=10),给予普通饲料喂养;高脂饮食组(HD, n=60),给予高脂饲料喂养。16周后,高脂饮食组大鼠体重均数高于普通饮食组大鼠20%,成功建立模型。所有大鼠过夜禁食后,麻醉状态下测量体重(BW),取静脉血测定血清甘油三酯(TG)、总胆固醇(TCH)、空腹血糖(FBG)、空腹胰岛素(FINS)及Visfatin。将40只达到肥胖模型标准的大鼠随机分为4组,每组各10只,在继续高脂饮食的同时给予不同干预。分别为:肥胖对照组(F组),二甲双胍干预组(M组),有氧运动干预组(T组),二甲双胍、有氧运动联合干预组(MT组)。M组予二甲双胍灌胃(200mg/kg.d),T组进行游泳运动,MT组予二甲双胍灌胃(200mg/kg.d)联合游泳运动,T组、F组及ND组等剂量蒸馏水灌胃。第22周再次测量体重(BW),取静脉血测定血清甘油三酯(TG)、总胆固醇(TCH)、空腹血糖(FBG)、空腹胰岛素(FINS)及Visfatin。处死大鼠后,采用免疫印迹法(Western blot方法)测定各组大鼠附睾脂肪,皮下脂肪,肝脏组织Visfatin蛋白的表达。
结果①高脂饲料喂养16周后,与ND组相比较,F组大鼠的体重、空腹血糖、空腹胰岛素、血清甘油三酯(TG)、总胆固醇(TCH)均升高(P <0.01或0.05)。②F组大鼠血清Visfatin较ND组升高(P < 0.01)。③与F组比较,M组、T组、MT组大鼠体重、空腹血糖、空腹胰岛素、血清甘油三酯(TG)、总胆固醇(TCH)均下降(P <0.01或0.05)。④M组、T组、MT组大鼠血清Visfatin较F组下降(P <0.01或0.05)。⑤M组、T组、MT组大鼠之间以上指标无明显差异。⑥F组附睾脂肪,皮下脂肪,肝脏组织Visfatin的蛋白表达较ND组增加(P <0.05)。⑦M组、T组、MT组附睾脂肪,皮下脂肪,肝脏组织Visfatin的蛋白表达较F组减少(P <0.05)。⑧BW、TG、TCH、FBG、FINS水平与血清Visfatin水平呈正相关(r=0.86, P<0.01; r=0.83, P<0.01; r=0.88, P<0.05; r=0.91, P<0.05; r=0.85, P<0.05 )
结论二甲双胍、有氧运动分别及联合应用可以一定程度改善高脂诱导肥胖大鼠代谢综合征状态,降低血清Visfatin浓度,并能下调附睾脂肪、皮下脂肪及肝脏Visfatin的蛋白表达。
Background The central link of metabolism syndrome is insulin resistence,the main reason of which is central obesity. Visfatin is a kind of secretory protein generated by adipose tissue,Which is mainly secreted by adipose tissue of internal organs, and also expressed in liver, pancreas, heart, placenta, lung, kidney etc. Researches show that Visfatin can play an insulin-like effect which is important to improve insulin sensitivity. As is known to all, both metformin and aerobic exercise can reduce weight and improve insulin sensitivity,but the relation between Visfatin and those two factors has been rarely reported.In this study,we try to observe the effects of aerobic exercise and metformin on Visfatin in obesity rats fed with high fat diet and to preliminarily investigate the mechanism.
Objective To observe the effects of metformin and aerobic exercise on Visfatin of serum,epididymis adipose tissue ,subcutaneous adipose tissue and liver in obesity rats fed with high fat diet.
Methods 70 male Sprague-Dawley(SD) rats were randomly divided into the normal diet group (ND) with 10 rats, fed with normal chow , the high fat diet group (HD) with the remaining 60, fed with high fat diet.After 16 weeks, the average BW of HD group were over 20% higher than ND group. All the rats were weighed under anesthesia. The triglyeride(TG), total cholesterol(TCH), fasting blood glucose(FBG), fasting insulin(FINS) and Visfatin in the serum were measured. Obesity model (n=40) was randomly divided into four groups accepting intervention for 6 weeks: group F,group M, group T and group MT,with 10 rats in each groups. Group M was treated with metformin (200mg/kg.d), group T was assigned to swimming exercise, and group MT was treated with the combination of metformin(200mg/kg.d) and swimming exercise. Group T, group F and group ND were treated with distilled water . The body weight (BW), triglyeride(TG), total cholesterol(TCH), fasting blood glucose(FBG), fasting insulin(FINS) and Visfatin in the serum were measured again at the end of 22nd week.After all the rats were killed, the protein levels of Visfatin in different tissues(epididymis adipose tissue ,subcutaneous adipose tissue and liver) were analyzed with Western blot.
Results①After 16 weeks of high-fat diet, BW, FBG, FINS ,TG and TCH levels of each group in obesity model were higher than that in ND group with a statistical significance (P <0.01 or P <0.05).②Visfatin in the serum in obesity model were higher than that in ND group(P < 0.01).③After 6 weeks’treatment BW, FBG, FINS ,TG and TCH levels in the group M, T and MT decreased compared to group F (P <0.01 or P <0.05).④Visfatin in the serum in the group M, T and MT decreased compared to group F(P <0.01 or P <0.05).⑤There is no statistical difference of BW, FBG, FINS ,TG, TCH and Visfatin levels in the group M, T and MT.⑥Visfatin protein expression levels of group F in EAT, SAT and LT increased compared to group ND(P <0.05).⑦Visfatin protein expression levels of group M, T and MT decreased in compared to group F in EAT, SAT and LT(P <0.05).⑧BW,TG、TCH、FBG、FINS were positively related to serum Visfatin levels(r=0.86, P <0.01; r=0.83, P <0.01; r=0.88, P <0.05; r=0.91, P <0.05; r=0.85, P <0.05 ).
Conclusion Metformin,aerobic exercise , the combination of metformin and aerobic exercise can improve the metabolism syndrome of rats fed with high fat diet to certain extent, and decrease the concentration of Visfatin of serum, epididymis fat, subcutaneous fat and liver in obesity rats.
目的观察二甲双胍,有氧运动分别及联合干预对高脂饲料诱导的肥胖大鼠血清、附睾脂肪、皮下脂肪、肝脏组织Visfatin及相关代谢指标的影响。
方法将70只雄性6周龄Sprague-Dawley(SD)大鼠随机分为普通饮食组(ND, n=10),给予普通饲料喂养;高脂饮食组(HD, n=60),给予高脂饲料喂养。16周后,高脂饮食组大鼠体重均数高于普通饮食组大鼠20%,成功建立模型。所有大鼠过夜禁食后,麻醉状态下测量体重(BW),取静脉血测定血清甘油三酯(TG)、总胆固醇(TCH)、空腹血糖(FBG)、空腹胰岛素(FINS)及Visfatin。将40只达到肥胖模型标准的大鼠随机分为4组,每组各10只,在继续高脂饮食的同时给予不同干预。分别为:肥胖对照组(F组),二甲双胍干预组(M组),有氧运动干预组(T组),二甲双胍、有氧运动联合干预组(MT组)。M组予二甲双胍灌胃(200mg/kg.d),T组进行游泳运动,MT组予二甲双胍灌胃(200mg/kg.d)联合游泳运动,T组、F组及ND组等剂量蒸馏水灌胃。第22周再次测量体重(BW),取静脉血测定血清甘油三酯(TG)、总胆固醇(TCH)、空腹血糖(FBG)、空腹胰岛素(FINS)及Visfatin。处死大鼠后,采用免疫印迹法(Western blot方法)测定各组大鼠附睾脂肪,皮下脂肪,肝脏组织Visfatin蛋白的表达。
结果①高脂饲料喂养16周后,与ND组相比较,F组大鼠的体重、空腹血糖、空腹胰岛素、血清甘油三酯(TG)、总胆固醇(TCH)均升高(P <0.01或0.05)。②F组大鼠血清Visfatin较ND组升高(P < 0.01)。③与F组比较,M组、T组、MT组大鼠体重、空腹血糖、空腹胰岛素、血清甘油三酯(TG)、总胆固醇(TCH)均下降(P <0.01或0.05)。④M组、T组、MT组大鼠血清Visfatin较F组下降(P <0.01或0.05)。⑤M组、T组、MT组大鼠之间以上指标无明显差异。⑥F组附睾脂肪,皮下脂肪,肝脏组织Visfatin的蛋白表达较ND组增加(P <0.05)。⑦M组、T组、MT组附睾脂肪,皮下脂肪,肝脏组织Visfatin的蛋白表达较F组减少(P <0.05)。⑧BW、TG、TCH、FBG、FINS水平与血清Visfatin水平呈正相关(r=0.86, P<0.01; r=0.83, P<0.01; r=0.88, P<0.05; r=0.91, P<0.05; r=0.85, P<0.05 )
结论二甲双胍、有氧运动分别及联合应用可以一定程度改善高脂诱导肥胖大鼠代谢综合征状态,降低血清Visfatin浓度,并能下调附睾脂肪、皮下脂肪及肝脏Visfatin的蛋白表达。
Background The central link of metabolism syndrome is insulin resistence,the main reason of which is central obesity. Visfatin is a kind of secretory protein generated by adipose tissue,Which is mainly secreted by adipose tissue of internal organs, and also expressed in liver, pancreas, heart, placenta, lung, kidney etc. Researches show that Visfatin can play an insulin-like effect which is important to improve insulin sensitivity. As is known to all, both metformin and aerobic exercise can reduce weight and improve insulin sensitivity,but the relation between Visfatin and those two factors has been rarely reported.In this study,we try to observe the effects of aerobic exercise and metformin on Visfatin in obesity rats fed with high fat diet and to preliminarily investigate the mechanism.
Objective To observe the effects of metformin and aerobic exercise on Visfatin of serum,epididymis adipose tissue ,subcutaneous adipose tissue and liver in obesity rats fed with high fat diet.
Methods 70 male Sprague-Dawley(SD) rats were randomly divided into the normal diet group (ND) with 10 rats, fed with normal chow , the high fat diet group (HD) with the remaining 60, fed with high fat diet.After 16 weeks, the average BW of HD group were over 20% higher than ND group. All the rats were weighed under anesthesia. The triglyeride(TG), total cholesterol(TCH), fasting blood glucose(FBG), fasting insulin(FINS) and Visfatin in the serum were measured. Obesity model (n=40) was randomly divided into four groups accepting intervention for 6 weeks: group F,group M, group T and group MT,with 10 rats in each groups. Group M was treated with metformin (200mg/kg.d), group T was assigned to swimming exercise, and group MT was treated with the combination of metformin(200mg/kg.d) and swimming exercise. Group T, group F and group ND were treated with distilled water . The body weight (BW), triglyeride(TG), total cholesterol(TCH), fasting blood glucose(FBG), fasting insulin(FINS) and Visfatin in the serum were measured again at the end of 22nd week.After all the rats were killed, the protein levels of Visfatin in different tissues(epididymis adipose tissue ,subcutaneous adipose tissue and liver) were analyzed with Western blot.
Results①After 16 weeks of high-fat diet, BW, FBG, FINS ,TG and TCH levels of each group in obesity model were higher than that in ND group with a statistical significance (P <0.01 or P <0.05).②Visfatin in the serum in obesity model were higher than that in ND group(P < 0.01).③After 6 weeks’treatment BW, FBG, FINS ,TG and TCH levels in the group M, T and MT decreased compared to group F (P <0.01 or P <0.05).④Visfatin in the serum in the group M, T and MT decreased compared to group F(P <0.01 or P <0.05).⑤There is no statistical difference of BW, FBG, FINS ,TG, TCH and Visfatin levels in the group M, T and MT.⑥Visfatin protein expression levels of group F in EAT, SAT and LT increased compared to group ND(P <0.05).⑦Visfatin protein expression levels of group M, T and MT decreased in compared to group F in EAT, SAT and LT(P <0.05).⑧BW,TG、TCH、FBG、FINS were positively related to serum Visfatin levels(r=0.86, P <0.01; r=0.83, P <0.01; r=0.88, P <0.05; r=0.91, P <0.05; r=0.85, P <0.05 ).
Conclusion Metformin,aerobic exercise , the combination of metformin and aerobic exercise can improve the metabolism syndrome of rats fed with high fat diet to certain extent, and decrease the concentration of Visfatin of serum, epididymis fat, subcutaneous fat and liver in obesity rats.
引文
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52. Pedersen,BK,Steensberg A,Fischer C,et al.Searching for the exercise factor:is IL-6 a candidate? [J].Journal of Muscle Research and Cell Motility 2003,24(2-3):113-9.
53.石敏,代芳,王长江等.吡格列酮和白细胞介素-6对3T3-L1脂肪细胞Visfatin mRNA表达的影响[J].安徽医科大学学报.2008,43(1):50-53
1.李秀钧,钱荣立.美国糖尿病学会第64届学术年会代谢综合征专题简介[J].中华糖尿病杂志,2004,12(5):377-9.
2. Samal B,Sun Y,Stearns G,et al .Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony-enhancing factor[J].Mol Cell Biol,1994,14(2):1431-7.
3. Fukuhara A, Matsuda M, Nishizawa M, et al. Visfatin: a protein secreted by visceral fat that mimics the effects of insulin[J].Science,2005, 307(5708):426-30.
4. Curat CA,Wegner V,Sengenes C,et a1.Macrophages in human visceral adipose tissue:increased accumulation in Obesity and a source of resistin and visfatin.[J]. Diabetologia.2006,49(4):744-7
5. Ognjanovic S, Bao S, Yamamoto SY,et al. Genomic organization of the gene coding for human pre-B-cell colony-enhancing factor and expression in human fetal membranes[J]. Mol Endocrinol, 2001,26(2):107-17.
6. Sethi JK,Vidal-Puig A.Visfatin:the missing link between intra-abdominal obesity and diabetes[J].Trends Mol Med,2005,11(8):344
7. Moschen AR,Kaser A,Enrich B,et a1.Visfatin,an adipocytokine with proinflammatory and immunomodulating properties [J].Immunol,2007,178(3):1748
8. Oki K,Yamane K,Kamei N,et a1.Circulatin related with inflammation,but not with insulin resistance[J].Clin Endocrinol(Oxf),2007,67(5):796
9. Chen M P,Chung FM , Chang DM, et al. Elevated plasma level of visfatin/Pre-B cell colony-enhancing factorin patients wth type 2 diabetes.[J].Clin Endocrinol Metab, 2006,91 (1):295-9.
10. Dogru T, Sonmez A, Tasci I, et al. Plasma visfatin levels in patients with newly diagnosed and untreated type 2 diabetes mellitus and impaired glucose tolerance[J]. Diabetes Res Clin Pract, 2007, 76(1):24-9.
11. Berndt J,K16ting N,Kralisch S.et a1.Plasma visfatin concentrations and fat depot-specific mRNA expression in humans[J].Diabetes,2005,54 (10):2911-6.
12.孙颖,刘德敏.内脏脂肪素:一种能模拟胰岛素作用的新脂肪细胞因子[J].国外医学内分泌学分册,2005,25(4):223.
13. Freedland Eric S. Role of a critical visceral adipose tissue threshold (CVATT) in metabolic syndrome:implications for controlling dietary carbohydrates. Nutrition & Metabolism, 2004,1:12.
14. Haider DG ,Schindler K ,Schaller G ,et al.Increased plasma visfatin concentrations in morbidly obese subjects are reduced after gastric banding [J].Clin Endocrinol Metab,2006,91 (4):1578-81.
15. Kl?ting N, Kl?ting I. Visfatin: gene expression in isolated adipocytes and sequence analysis in obese WOKW rats compared with lean control rats[J]. Biochem Biophys Res Commun, 2005, 332(4): 1070-2.
16. Dahl TB,Yndestad A,Skjelland M,et a1.Increased expression of visfatin in ma crophages of human unstable carotid an d coronary atherosclerosis:possible role in inflammation an d plaque destabilization[J].Circulation,2007,115(8):972
17. Takebayashi K,Suetsugu M,Wakabayashi S,et al.Association between plasma visfatin and vascular endothelial function in patients with type 2 diabetes mellitus[J].Metabolism,2007,56(4):451
18. Kralisch S, Klein J, Lossner U, et al. Hormonal regulation of the novel adipocytokine visfatin in 3T3-L1 adipocytes[J]. Endocrinol, 2005, 185(3): R1-8.
19. Haider DG, Schaller G, Kapiotis S, et al. The release of the adipocytokine visfatin is regulated by glucose and insulin[J]. Diabetologia, 2006,49(8):1909-14.
20. Moschen AR,Kaser A,Enrich B,et al.Visfafin,an adipecytokine with proinflammatory and immunomodulating properties[J].Immunology,2007,178(3):1748-58.
21. Choi KC, Ryu OH, Lee KW, et al. Effect of PPAR-alpha and -gamma agonist on the expression of visfatin, adiponectin, and TNF-alpha in visceral fat of OLETF rats[J]. Biochem Biophys Res Commun,2005,336(3):747-53
22. Haider DG, Mittermayer F, Schaller G, et al. Free fatty acids normalize arosiglitazone-induced visfatin release[J].Am J Physiol Endocrinol Metab,2006,291(5): E885-90.
23. Haider DG, Schindler K, Mittermayer F, et al. Effect of rosiglitazone on visfatin and retinol-binding protein-4 plasma concentrations in HIV-positive patients[J]. Clin Pharmacol Ther, 2007, 81(4): 580-5.
24.张德园,王长江,代芳等.PPARγ配体罗格列酮和GW9662对3T3-L1脂肪细胞内脏脂肪素mRNA表达的影响[J].安徽医科大学学报,2008,43(5):504-8
25. Pfützner A, Marx N, Walcher D, et al. Impact of rosiglitazone on visfatin and adiponectin plasma concentrations in patients with type 2 diabetes and coronary artery disease[J]. Clin Lab, 2008,54(7-8):237-41.
26. Hammarstedt A,Pihlajamitki J,Sopasakis VR, et al.Visfatin is an adipokine but it is not regulated by thiazolidinediones[J]. Clin Endocrinol Metab,2006,91(3):1181-4
27. Erdem G, Dogru T, Tasci I, et al . The effects of pioglitazone and metformin on plasma visfatin levels in patients with treatment naive type 2 diabetes mellitus[J]. Diabetes Res Clin Pract,2008 ,82(2):214-8.
28. Domonik GH,Johannes Pleiner,Mario Francesconi,et al. Exercise tranning lowers plasma Visfatin concentrations in patients with type 1 diabetes[J].J Clin Endocrinol Metab, 2006 ;91(11):4702-4.
29. Choi KM, Kim JH, Cho GJ, et al.Effect of exercise training on plasma visfatin and eotaxin levels.Eur J Endocrinol. 2007 Oct;157(4):437-42.
30.尚敬,陈璐璐,孙晖等.运动干预对高脂喂养大鼠脂肪组织内脏脂肪素表达的影响中国现代医学杂志2008;18(5):551-554.
31. Frydelund-Larsen L, Akerstrom T, Nielsen S, et al. Visfatin mRNA expression in human subcutaneous adipose tissue is regulated by exerciseAm J Physiol Endocrinol Metab. 2007 Jan;292(1):E24-31. Epub 2006 Jul 25.
32. Kadoglou NP, Tsanikidis H, Kapelouzou A, et al.2009 Oct 6. [Epub ahead of print]Effects of rosiglitazone and metformin treatment on apelin, visfatin, and ghrelin levels in patients with type 2 diabetes mellitus. 2008 Dec 24. [Epub ahead of print]
33. Erdem G, Dogru T, Tasci I, et al. the effects of pioglitazone and metformin on plasma visfatin levels in patients with treatment naive type 2 diabetes mellitus. [J].Diabetes Res Clin Pract. 2008 ,82(2):214-8.
34. Ozkaya M, Cakal E, Ustun Y, et al.Effect of metformin on serum visfatin levels in patients with polycystic ovary syndrome.[J] Fertil Steril.2010,93(3):880-4
2.Samal B,Sun Y,Stearns G,et al.Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony-enhancing factor[J].Mol Cell Biol,1994,14(2):1431-37.
3. Fukuhara A, Matsuda M, Nishizawa M, et al. Visfatin: a protein secreted by visceral fat that mimics the effects of insulin[J].Science,2005, 307(5708):426-30.
4.Ognjanovic S, Bao S, Yamamoto SY,et al. Genomic organization of the gene coding for human pre-B-cell colony-enhancing factor and expression in human fetal membranes[J]. J Mol Endocrinol, 2001,26(2):107-17.
5. Sethi JK,Vidal-Puig A.Visfatin:the missing link between intra-abdominal obesity and diabetes[J].Trends in Molecular Medicine,2005,11(8):344-7
6. MoschenAR,Kaser A,Enrich B,et a1.Visfatin,an adipocytokine with proinflammatory and immunomodulating properties[J].The Journal of Immunology,2007,178(3):1748-58
7.MacLaren R, Cui W, Cianflone K. Visfatin expression is hormonally regulated bymetabolic and sex hormones in 3T3-L1 pre-adipocytes and adipocytes[J]. Diabetes Obes Metab, 2007, 9(4): 490-7.
8.Kralisch S, Klein J, Lossner U, et al. Hormonal regulation of the novel adipocytokine visfatin in 3T3-L1 adipocytes[J]. J Endocrinol, 2005, 185(3): R1-8.
9.Haider DG, Schaller G, Kapiotis S, et al. The release of the adipocytokine visfatin is regulated by glucose and insulin[J]. Diabetologia, 2006,49(8):1909-14.
10.Kralisch S, Klein J, Lossner U, et al. Interleukin-6 is a negative regulator of visfatin gene expression in 3T3-L1 adipocytes[J]. Am J Physiol Endocrinol Metab, 2005, 289(4):E586-90.
11.Haider DG, Mittermayer F, Schaller G, et al. Free fatty acids normalize a rosiglitazone-induced visfatin release[J]. Am J Physiol Endocrinol Metab,2006,291(5):E885-90.
12.Haider DG, Schindler K, Mittermayer F, et al. Effect of rosiglitazone on visfatin and retinol-binding protein-4 plasma concentrations in HIV-positive patients[J]. Clin Pharmacol Ther, 2007, 81(4): 580-5.
13.Choi KC, Ryu OH, Lee KW, et al. Effect of PPAR-alpha and -gamma agonist on the expression of visfatin, adiponectin, and TNF-alpha in visceral fat of OLETF rats[J]. Biochem Biophys Res Commun,2005,336(3):747-53
14.Pfützner A, Marx N, Walcher D, et al. Impact of rosiglitazone on visfatin and adiponectin plasma concentrations in patients with type 2 diabetes and coronary artery disease[J]. Clin Lab, 2008,54(7-8):237-41.
15.Caixàs A,Tirado R, Vendrell J, et al. Plasma visfatin concentrations increase in both hyper and hypothyroid subjects after normalisation of thyroid function and are not related to insulin resistance, anthropometric or inflammatory parameters[J]. Clin Endocrinology,2009,71(5):733-8
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25. Dahl TB,Yndestad A,Skjelland M,et a1.Increased expression of visfatin in ma crophages of human unstable carotid an d coronary atherosclerosis:possible role in inflammation an d plaque destabilization[J].Circulation,2007,115(8):972
26. Chen MP, Chung FM, Chang DM, et al. Elevated plasma level of visfatin/pre-B cell colony-enhancing factor in patients with type 2 diabetes mellitus[J].Clin Endocrinol Metab 2006; 91:295-9.
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39.Erdem G, Dogru T, Tasci I,etl. the effects of pioglitazone and metformin on plasma visfatin levels in patients with treatment naive type 2 diabetes mellitus[J].Diabetes Res Clin Pract. 2008 ,82(2):214-8.
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46.Choi KM, Kim JH, Cho GJ, et al.Effect of exercise training on plasma visfatin and eotaxin levels.Eur J Endocrinol. 2007,157(4):437-42.
47.尚敬,陈璐璐,孙晖等.运动干预对高脂喂养大鼠脂肪组织内脏脂肪素表达的影响[J].中国现代医学杂志2008,18(5):551-4.
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51. Pedersen BK, Febbraio Muscle-derived interleukin-6--a possible link between skeletal muscle, adipose tissue, liver, and brain[J].Brain,Behavior,and Immunity,2005,19(5):371-6.
52. Pedersen,BK,Steensberg A,Fischer C,et al.Searching for the exercise factor:is IL-6 a candidate? [J].Journal of Muscle Research and Cell Motility 2003,24(2-3):113-9.
53.石敏,代芳,王长江等.吡格列酮和白细胞介素-6对3T3-L1脂肪细胞Visfatin mRNA表达的影响[J].安徽医科大学学报.2008,43(1):50-53
1.李秀钧,钱荣立.美国糖尿病学会第64届学术年会代谢综合征专题简介[J].中华糖尿病杂志,2004,12(5):377-9.
2. Samal B,Sun Y,Stearns G,et al .Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony-enhancing factor[J].Mol Cell Biol,1994,14(2):1431-7.
3. Fukuhara A, Matsuda M, Nishizawa M, et al. Visfatin: a protein secreted by visceral fat that mimics the effects of insulin[J].Science,2005, 307(5708):426-30.
4. Curat CA,Wegner V,Sengenes C,et a1.Macrophages in human visceral adipose tissue:increased accumulation in Obesity and a source of resistin and visfatin.[J]. Diabetologia.2006,49(4):744-7
5. Ognjanovic S, Bao S, Yamamoto SY,et al. Genomic organization of the gene coding for human pre-B-cell colony-enhancing factor and expression in human fetal membranes[J]. Mol Endocrinol, 2001,26(2):107-17.
6. Sethi JK,Vidal-Puig A.Visfatin:the missing link between intra-abdominal obesity and diabetes[J].Trends Mol Med,2005,11(8):344
7. Moschen AR,Kaser A,Enrich B,et a1.Visfatin,an adipocytokine with proinflammatory and immunomodulating properties [J].Immunol,2007,178(3):1748
8. Oki K,Yamane K,Kamei N,et a1.Circulatin related with inflammation,but not with insulin resistance[J].Clin Endocrinol(Oxf),2007,67(5):796
9. Chen M P,Chung FM , Chang DM, et al. Elevated plasma level of visfatin/Pre-B cell colony-enhancing factorin patients wth type 2 diabetes.[J].Clin Endocrinol Metab, 2006,91 (1):295-9.
10. Dogru T, Sonmez A, Tasci I, et al. Plasma visfatin levels in patients with newly diagnosed and untreated type 2 diabetes mellitus and impaired glucose tolerance[J]. Diabetes Res Clin Pract, 2007, 76(1):24-9.
11. Berndt J,K16ting N,Kralisch S.et a1.Plasma visfatin concentrations and fat depot-specific mRNA expression in humans[J].Diabetes,2005,54 (10):2911-6.
12.孙颖,刘德敏.内脏脂肪素:一种能模拟胰岛素作用的新脂肪细胞因子[J].国外医学内分泌学分册,2005,25(4):223.
13. Freedland Eric S. Role of a critical visceral adipose tissue threshold (CVATT) in metabolic syndrome:implications for controlling dietary carbohydrates. Nutrition & Metabolism, 2004,1:12.
14. Haider DG ,Schindler K ,Schaller G ,et al.Increased plasma visfatin concentrations in morbidly obese subjects are reduced after gastric banding [J].Clin Endocrinol Metab,2006,91 (4):1578-81.
15. Kl?ting N, Kl?ting I. Visfatin: gene expression in isolated adipocytes and sequence analysis in obese WOKW rats compared with lean control rats[J]. Biochem Biophys Res Commun, 2005, 332(4): 1070-2.
16. Dahl TB,Yndestad A,Skjelland M,et a1.Increased expression of visfatin in ma crophages of human unstable carotid an d coronary atherosclerosis:possible role in inflammation an d plaque destabilization[J].Circulation,2007,115(8):972
17. Takebayashi K,Suetsugu M,Wakabayashi S,et al.Association between plasma visfatin and vascular endothelial function in patients with type 2 diabetes mellitus[J].Metabolism,2007,56(4):451
18. Kralisch S, Klein J, Lossner U, et al. Hormonal regulation of the novel adipocytokine visfatin in 3T3-L1 adipocytes[J]. Endocrinol, 2005, 185(3): R1-8.
19. Haider DG, Schaller G, Kapiotis S, et al. The release of the adipocytokine visfatin is regulated by glucose and insulin[J]. Diabetologia, 2006,49(8):1909-14.
20. Moschen AR,Kaser A,Enrich B,et al.Visfafin,an adipecytokine with proinflammatory and immunomodulating properties[J].Immunology,2007,178(3):1748-58.
21. Choi KC, Ryu OH, Lee KW, et al. Effect of PPAR-alpha and -gamma agonist on the expression of visfatin, adiponectin, and TNF-alpha in visceral fat of OLETF rats[J]. Biochem Biophys Res Commun,2005,336(3):747-53
22. Haider DG, Mittermayer F, Schaller G, et al. Free fatty acids normalize arosiglitazone-induced visfatin release[J].Am J Physiol Endocrinol Metab,2006,291(5): E885-90.
23. Haider DG, Schindler K, Mittermayer F, et al. Effect of rosiglitazone on visfatin and retinol-binding protein-4 plasma concentrations in HIV-positive patients[J]. Clin Pharmacol Ther, 2007, 81(4): 580-5.
24.张德园,王长江,代芳等.PPARγ配体罗格列酮和GW9662对3T3-L1脂肪细胞内脏脂肪素mRNA表达的影响[J].安徽医科大学学报,2008,43(5):504-8
25. Pfützner A, Marx N, Walcher D, et al. Impact of rosiglitazone on visfatin and adiponectin plasma concentrations in patients with type 2 diabetes and coronary artery disease[J]. Clin Lab, 2008,54(7-8):237-41.
26. Hammarstedt A,Pihlajamitki J,Sopasakis VR, et al.Visfatin is an adipokine but it is not regulated by thiazolidinediones[J]. Clin Endocrinol Metab,2006,91(3):1181-4
27. Erdem G, Dogru T, Tasci I, et al . The effects of pioglitazone and metformin on plasma visfatin levels in patients with treatment naive type 2 diabetes mellitus[J]. Diabetes Res Clin Pract,2008 ,82(2):214-8.
28. Domonik GH,Johannes Pleiner,Mario Francesconi,et al. Exercise tranning lowers plasma Visfatin concentrations in patients with type 1 diabetes[J].J Clin Endocrinol Metab, 2006 ;91(11):4702-4.
29. Choi KM, Kim JH, Cho GJ, et al.Effect of exercise training on plasma visfatin and eotaxin levels.Eur J Endocrinol. 2007 Oct;157(4):437-42.
30.尚敬,陈璐璐,孙晖等.运动干预对高脂喂养大鼠脂肪组织内脏脂肪素表达的影响中国现代医学杂志2008;18(5):551-554.
31. Frydelund-Larsen L, Akerstrom T, Nielsen S, et al. Visfatin mRNA expression in human subcutaneous adipose tissue is regulated by exerciseAm J Physiol Endocrinol Metab. 2007 Jan;292(1):E24-31. Epub 2006 Jul 25.
32. Kadoglou NP, Tsanikidis H, Kapelouzou A, et al.2009 Oct 6. [Epub ahead of print]Effects of rosiglitazone and metformin treatment on apelin, visfatin, and ghrelin levels in patients with type 2 diabetes mellitus. 2008 Dec 24. [Epub ahead of print]
33. Erdem G, Dogru T, Tasci I, et al. the effects of pioglitazone and metformin on plasma visfatin levels in patients with treatment naive type 2 diabetes mellitus. [J].Diabetes Res Clin Pract. 2008 ,82(2):214-8.
34. Ozkaya M, Cakal E, Ustun Y, et al.Effect of metformin on serum visfatin levels in patients with polycystic ovary syndrome.[J] Fertil Steril.2010,93(3):880-4