针刺干预胰岛素抵抗模型大鼠胰岛素信号转导途径中GLUT4和Akt2 mRNA表达的研究
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摘要
胰岛素抵抗(IR)可引起的一系列病理生理变化,是包括脑卒中在内的多种疾病的重要危险因素。针刺对脑卒中、糖尿病、肥胖等IR相关疾病的疗效早已得到了国内外同行的公认。
目的:通过动物实验阐明针刺对胰岛素抵抗的干预作用。以反映IR水平的血液生化学指标以及糖代谢胰岛素信号转导途径中的关键蛋白GLUT4(葡萄糖转运蛋4)和Akt2(蛋白激酶B_β)为对象,运用头穴丛刺、背俞穴针刺等不同针刺方法进行干预。探讨IR模型大鼠胰岛素信号转导途径中GLUT4和Akt2 mRNA表达的变化特点和针刺干预作用——防治脑卒中及其他IR相关疾病的机制。
方法:将健康Wistar雄性大鼠随机分为正常对照组、模型组、头针组、和背俞穴针刺组,每组8只。采用高脂膳食喂养建立IR大鼠模型,头针组采用头穴丛刺法,背俞穴针刺组取脾俞、肾俞加胰俞穴电针治疗,连续治疗两周;采用放射免疫分析方法测定血浆胰岛素(FINS),全自动生化分析仪检测大鼠空腹血糖(FBG)、胆固醇(TC)、甘油三酯(TG),测算胰岛素敏感性指数(ISI)及体重(BW)等相关指标,明确IR模型建立成功及针刺的疗效;采用免疫组化观察各组大鼠骨骼肌细胞GLUT4和Akt2的表达;应用逆转录聚合酶链反应(RT-PCR)技术对相关分子m RNA表达进行观测和定量分析研究。
结果:1.模型组BW、FINS、TG均较正常组明显升高,而ISI却明显下降(P＜0.05);各针刺组大鼠FINS较模型组明显降低,ISI则明显上升(p＜0.05),不同针刺组之间无显著性差异(P＞0.05);模型组较正常组FBG、TC升高无统计学意义(P＞0.05);各针刺组较模型组BW、TG降低无统计学意义(P＞0.05)。2.免疫组化的结果显示IR模型大鼠骨骼肌GLUT4、Akt2的表达较正常组明显减弱,通过针刺干预可以使GLUT4、Akt2的表达增强,但是背俞穴组和头针组之间的差别不大。3.RT-PCR结果显示:模型组GLUT4 mRNA含量均较正常组明显降低(p＜0.05),针刺组GLUT4 mRNA含量明显高于模型组(p＜0.05),不同针刺组之间无显著性差异(P＞0.05);模型组骨骼肌Akt2 mRNA表达较正常对照组大鼠明显降低(p＜0.01);而两组针刺组较模型组明显升高(p＜0.01),不同针刺组之间无显著性差异(P＞0.05)。
结论:1.针刺显著提高IR模型大鼠胰岛素敏感性指数,使之趋向正常,改善了胰岛素抵抗状况,从而达到防治脑卒中及其他IR相关疾病的目的。头针组和背俞穴针刺组之间疗效差别无统计学意义。2.针刺可使IR模型大鼠GLUT4基因转录增加,导致GLUT4蛋白含量增加,其结果是外周组织细胞转运和利用葡萄糖的能力增加,这是针刺改善IR状况的机制之一。3.针刺可以使IR大鼠胰岛素信号转导途径中Akt2表达增强和mRNA含量增加,促进了胰岛素PI3-K/Akt途径信号通路中GLUT4的转位,针刺可能通过胰岛素受体后机制中的主要途径之一—PI3-K/Akt信号转导通路改善IR大鼠外周组织对胰岛素的抵抗,降低高胰岛素血症,也是针刺改善IR状况的机制之一。
Implication of insulin rasistance(IR) leads to a series of changes on pathology physiology,which are significant risk factors to many disease included in stroke. And curative effects of acupuncture on stroke ,diabetes adipositas and so on which connected with IR have been generally accepted.
Objective:To develop a rat model of IR,and to study the effect of acupuncture on expression of GLUT4 (glucose transporter 4) and Akt2 (protein kinase Bp) in somatic muscles of IR rats and the mechanism of acupuncture therapy in IR,which can prevent and cure stroke and other disease correlated with IR.
Method: 1 .Male Wistar rats were were randomly divded into 4 groups: The IR model rats without treatment group(M group), the IR rats with head acupuncture treatment group(HA group), the IR rats with back Shu-acupoint acupuncture treatment group(SA group) and the normal controls group(N group) and each group has 8 rats. The rats of M,HA and SA groups were given the high fat diets for 4 weeks to be IR model rats. Then the HA group were treated with cluster acupuncture on scalp points and the SA group were treated with Pishu Shenshu and Yishu acupoints electroacupuncture for 2 weeks.2.The blood samples were collected to evaluate FINS,FBG,TC and TG, to calculate ISI ( insulin sensitivity index) and measure BW to identify the IR of model rats and observe the curative effect of acupuncture. 3 . The protein expression of GLUT4 and Akt2 in rats skeletal muscle were observed by immunohistochemistry. 4.The GLUT4 and Akt2 mRNA of skeletal muscle was determined with RT-PCR(reverse transcription-polymerase chain raction).
Results: 1. Compared with N group,the BW,FINS and TG in M group were significantly increased, and ISI was decreased(P<0.05).Compared with M group,the BW,FINS in HA group and SA group was significantly decreased, and ISI was increased (P<0.05), withnot statistical significance between HA group and SA group (P>0.05).There was no statistical significance of the increase of FBG and TC in M group compared with N group, as well as the decrease of BW and TG in HA group and SA group compared with M group(P>0.05).2. The result of immunohistochemistry was shown the protein expression of GLUT4 and Akt2 in M group rats skeletal muscle was weaker than that in N group. And there was stronger expression in HA group and SA group than that in M group without significant defference between acupuncture groups.3. The result of RT-PCR was shown the expression of GLUT4 mRNA in M group rats skeletal muscle was significantly decreased,compared with N group (P<0.05) .And compared with M group, it was increased in HA group and SA group(P<0.05) without significant defference between them(P>0.05).The expression of Akt2 mRNA in M group rats skeletal muscle was significantly decreased,compared with N group (P<0.01) .And compared with M group, it was increased in HA group and SA group(P<0.01) without significant defference between them(P>0.05).
Conclusions: 1 .IR can be ameliorated by acupuncture without significant defference between HA group and SA group,which can prevent and cure stroke and other disease correlated with IR. 2. The genetic transcription of GLUT4 and the ability of conveying and utilizing glycose in IR rats skeletal muscle cells can be enhanced by acupuncture, which is one of the amelioration mechanisms of acupuncture.3. Acupuncture may enhance the Akt2 expression and raise the amount of Akt2 mRNA in IR rats , which enhances the transposition of GLUT4 in the PI3-K/Akt signaling pathway, contributing to the main mechanismof improved post-receptor IR and decreased hyperinsulinemia in IR rats,which also is one of the amelioration mechanisms of acupuncture.
目的:通过动物实验阐明针刺对胰岛素抵抗的干预作用。以反映IR水平的血液生化学指标以及糖代谢胰岛素信号转导途径中的关键蛋白GLUT4(葡萄糖转运蛋4)和Akt2(蛋白激酶B_β)为对象,运用头穴丛刺、背俞穴针刺等不同针刺方法进行干预。探讨IR模型大鼠胰岛素信号转导途径中GLUT4和Akt2 mRNA表达的变化特点和针刺干预作用——防治脑卒中及其他IR相关疾病的机制。
方法:将健康Wistar雄性大鼠随机分为正常对照组、模型组、头针组、和背俞穴针刺组,每组8只。采用高脂膳食喂养建立IR大鼠模型,头针组采用头穴丛刺法,背俞穴针刺组取脾俞、肾俞加胰俞穴电针治疗,连续治疗两周;采用放射免疫分析方法测定血浆胰岛素(FINS),全自动生化分析仪检测大鼠空腹血糖(FBG)、胆固醇(TC)、甘油三酯(TG),测算胰岛素敏感性指数(ISI)及体重(BW)等相关指标,明确IR模型建立成功及针刺的疗效;采用免疫组化观察各组大鼠骨骼肌细胞GLUT4和Akt2的表达;应用逆转录聚合酶链反应(RT-PCR)技术对相关分子m RNA表达进行观测和定量分析研究。
结果:1.模型组BW、FINS、TG均较正常组明显升高,而ISI却明显下降(P＜0.05);各针刺组大鼠FINS较模型组明显降低,ISI则明显上升(p＜0.05),不同针刺组之间无显著性差异(P＞0.05);模型组较正常组FBG、TC升高无统计学意义(P＞0.05);各针刺组较模型组BW、TG降低无统计学意义(P＞0.05)。2.免疫组化的结果显示IR模型大鼠骨骼肌GLUT4、Akt2的表达较正常组明显减弱,通过针刺干预可以使GLUT4、Akt2的表达增强,但是背俞穴组和头针组之间的差别不大。3.RT-PCR结果显示:模型组GLUT4 mRNA含量均较正常组明显降低(p＜0.05),针刺组GLUT4 mRNA含量明显高于模型组(p＜0.05),不同针刺组之间无显著性差异(P＞0.05);模型组骨骼肌Akt2 mRNA表达较正常对照组大鼠明显降低(p＜0.01);而两组针刺组较模型组明显升高(p＜0.01),不同针刺组之间无显著性差异(P＞0.05)。
结论:1.针刺显著提高IR模型大鼠胰岛素敏感性指数,使之趋向正常,改善了胰岛素抵抗状况,从而达到防治脑卒中及其他IR相关疾病的目的。头针组和背俞穴针刺组之间疗效差别无统计学意义。2.针刺可使IR模型大鼠GLUT4基因转录增加,导致GLUT4蛋白含量增加,其结果是外周组织细胞转运和利用葡萄糖的能力增加,这是针刺改善IR状况的机制之一。3.针刺可以使IR大鼠胰岛素信号转导途径中Akt2表达增强和mRNA含量增加,促进了胰岛素PI3-K/Akt途径信号通路中GLUT4的转位,针刺可能通过胰岛素受体后机制中的主要途径之一—PI3-K/Akt信号转导通路改善IR大鼠外周组织对胰岛素的抵抗,降低高胰岛素血症,也是针刺改善IR状况的机制之一。
Implication of insulin rasistance(IR) leads to a series of changes on pathology physiology,which are significant risk factors to many disease included in stroke. And curative effects of acupuncture on stroke ,diabetes adipositas and so on which connected with IR have been generally accepted.
Objective:To develop a rat model of IR,and to study the effect of acupuncture on expression of GLUT4 (glucose transporter 4) and Akt2 (protein kinase Bp) in somatic muscles of IR rats and the mechanism of acupuncture therapy in IR,which can prevent and cure stroke and other disease correlated with IR.
Method: 1 .Male Wistar rats were were randomly divded into 4 groups: The IR model rats without treatment group(M group), the IR rats with head acupuncture treatment group(HA group), the IR rats with back Shu-acupoint acupuncture treatment group(SA group) and the normal controls group(N group) and each group has 8 rats. The rats of M,HA and SA groups were given the high fat diets for 4 weeks to be IR model rats. Then the HA group were treated with cluster acupuncture on scalp points and the SA group were treated with Pishu Shenshu and Yishu acupoints electroacupuncture for 2 weeks.2.The blood samples were collected to evaluate FINS,FBG,TC and TG, to calculate ISI ( insulin sensitivity index) and measure BW to identify the IR of model rats and observe the curative effect of acupuncture. 3 . The protein expression of GLUT4 and Akt2 in rats skeletal muscle were observed by immunohistochemistry. 4.The GLUT4 and Akt2 mRNA of skeletal muscle was determined with RT-PCR(reverse transcription-polymerase chain raction).
Results: 1. Compared with N group,the BW,FINS and TG in M group were significantly increased, and ISI was decreased(P<0.05).Compared with M group,the BW,FINS in HA group and SA group was significantly decreased, and ISI was increased (P<0.05), withnot statistical significance between HA group and SA group (P>0.05).There was no statistical significance of the increase of FBG and TC in M group compared with N group, as well as the decrease of BW and TG in HA group and SA group compared with M group(P>0.05).2. The result of immunohistochemistry was shown the protein expression of GLUT4 and Akt2 in M group rats skeletal muscle was weaker than that in N group. And there was stronger expression in HA group and SA group than that in M group without significant defference between acupuncture groups.3. The result of RT-PCR was shown the expression of GLUT4 mRNA in M group rats skeletal muscle was significantly decreased,compared with N group (P<0.05) .And compared with M group, it was increased in HA group and SA group(P<0.05) without significant defference between them(P>0.05).The expression of Akt2 mRNA in M group rats skeletal muscle was significantly decreased,compared with N group (P<0.01) .And compared with M group, it was increased in HA group and SA group(P<0.01) without significant defference between them(P>0.05).
Conclusions: 1 .IR can be ameliorated by acupuncture without significant defference between HA group and SA group,which can prevent and cure stroke and other disease correlated with IR. 2. The genetic transcription of GLUT4 and the ability of conveying and utilizing glycose in IR rats skeletal muscle cells can be enhanced by acupuncture, which is one of the amelioration mechanisms of acupuncture.3. Acupuncture may enhance the Akt2 expression and raise the amount of Akt2 mRNA in IR rats , which enhances the transposition of GLUT4 in the PI3-K/Akt signaling pathway, contributing to the main mechanismof improved post-receptor IR and decreased hyperinsulinemia in IR rats,which also is one of the amelioration mechanisms of acupuncture.
引文
1 WHO Task Force on Stroke and Other Cerebrovascular Disorders recom-mendations on stroke prevention,diagnosis,and therapy.Stroke,1989,20:1407.
2 姜欣荣,邓浩萍.胰岛素抵抗与相关疾病[J].医学综述,1998,4(9):500-501.
3 李秀钧,胰岛素抵抗综合征,人民卫生出版社.2001.
4 杨丽娟.胰岛素抵抗及其临床处理[J].现代康复,2000,4(5):760.
5 Reaven GM,Role of insulin resistance in human disease.Diabetes,1988,37(12):1595.
6 WHO.Definition,Diagnosis and classification of Diabetes Mellitus and its Complications.Report of a WHO Consultation,1999,31-34.
7 Bloomgaren ZT.American Diabetes Association annual meeting,insulin rasistance,esercise and obesxity.Diabetes Care,1999,22:517-522.
8 Jia WP,Xiang KS,Chen L,et al.Epidemiologic study on metabolic syndrome in mormal and overweight Chinese in Shanghai.Diabetes,2000(snppl 1)49:A184.
9 李秀钧.胰岛素抵抗及胰岛素抵抗综合征研究展望[J].中华内分泌代谢杂志,2000,16(5):274-276.
10 Festa A,D Agostino R,Jr,Mykkanen L.LDL particle size in relalion to insulin,proinsnlin,and insulin sensitivity.The Insulin Resistance Atherosderosis Study.Diabetes Care,1999,22:1688-1693.
11 Groop LC.Insulin resistance:the fundamentatl trigger of type 2 diabetes mellitus.Obesity & Metabolism.1999,1:2-9.
12 程歆琦,鄢盛恺,宋耀虹.代谢综合征与血脂异常[J].国外医学.临床生物化学与检验学分册,2005,(02):102.
13 Alberti KGMM,Zimmet PZ for the WHO consultation.Definition,diagnosis and classification of diabetes mellitus and its complications-part 1:diagnosis and classification of diabetes mellitus provisional report of a who consultation.Diabetic Medicine,1998,539-553.
14 Shinozaki K,Naritomi H,Shimizu T,et al.Role of insulin resistanceassociated with compenosatory hypewinsulinemia in ischemic stroke.Strok 1996,27:37-43.
15 Lindahl B,Dinesen B,Eliasson M,et al.High proinsulin levels precede first-ever stroke in a nondiabetic population.Stroke 2000,31:2936-2941.
16 KuusistoJ,Mykkanen L,Pyorala K,et al.Non-insulin-dependent diabetes and its metabolic control are important predirtors of stroke in elderly subjects.Strok 1994,25:1157-1164.
17 Wanamethee SC,Perry IJ,Shaper AG.Nonfasting serum glucose and insulin concentrations and the risk of stroke.Strok 1999,30:1780-1786.
18 Lakka HM,Lakka TA,Tuomilehtom J,et al.Hyoerinsulinemia and the risk of cardiovascular death and acute coronary and cerebrovascular evens in men.Arch Intern Med 2000,160:1160-1168.
19 Pyoeala M,Miettinen H,Laakso M,et al.Hyperinsulinemia and the risk of stroke in healthy middle aged men.The 22 year follow-up results of the Helsinki policemen study.Strok 1998,29:1860-1866.
20 Folsom AR,Rasmussen ML,Chambless LK,et al.Prospective associations of fasting insulin body fat distribution and diabetes with risk of ischemic stroke.Diabetes Care 1999,22:1077-1083.
21 邹立,彭凯润,张幸运.胰岛素抵抗与脑梗死关系的研究[J].临床神经病学杂志,1996,9:152.
22 何丽彬,周旭光,孙伟峰,等.胰岛素抵抗及其与缺血性脑血管病关系的研究[J]黑龙江医学,2001,25(3):165-167.
23 Yalow R,Berson SA.Immunoassay of endogenous plasma insulin in man.J Clin Invest.1960,39:1157-1175.
24 李光伟.胰岛素敏感性评估及其在临床研究中的应用[J].中华内分泌代谢杂志,2000,16(3):198-200.
25 Bergman RN,Finegood DT,Ader M.Assessment of insulin sensitivity in vivo.EndocrRev.1985,6(1):45-86.
26 张家庆.新的HOMA-IR—从空腹血糖、空腹胰岛素测胰岛素抵抗[J].中 华糖尿病杂志,2005,3(4):245-246.
27 李光伟,潘孝仁,Stephen Lillioja,et al.检测人群胰岛素敏感性的一项新指数[J].中华内科杂志,1993,32(10):656-660.
28 陈为安.胰岛素抵抗、血脂异常与急性脑梗死关系的初步研究[D].苏州大学硕士论文,2002:15-18.
29 都健,赵玉岩,谢辉,等.喂养型胰岛素抵抗动物模型的建立与评价[J].中国医科大学学报,2002,31(5)343-346.
30 Scherrer U,Sartori C.Insulin as a vascular and sympathoex-citatory hormone.Lmplication for blood pressure regulation,insulin sensitivity,and cardiovascular morbidity.Circulation,1997,96:4101-4113.
31 Bonora E,Willeit J,Kiechl S,et al.Relationship between insulin and carotid atherosclerosis in the general population[J].Stroke,1997,28:1147.
32 黄海泉.胰岛素抵抗与动脉粥样硬化[J]临床荟萃,2005,(13):45.
33 Byberg L,Siegbahn A,Berglund L,et al.Plasminogen activator unhibitor activity is independently relared to both insulin sensrtivity and serum triglycerides in 70-year old men.Arterioselerosis 1998,18(2):258-264.
34 柳太云.胰岛素抵抗、高脂血症与缺血.性脑卒中[J].临床神经病学杂志,1999,12(1):32-33.
35 张熙泉,商淑梅,梁继舜,等.胰岛素抵抗与高血压性脑出血关系初步探讨[J].中国神经免疫和神经病学杂志,1999,6(1):36-40.
36 王振才,陈晓红,张建宏,等.胰岛素抵抗与正常血压脑出血及脑梗塞关系的探讨[J].脑与神经疾病杂志,1998,6(3):135-137.
37 旃培艳,张临洪.胰岛素抵抗与糖尿病腔隙性梗塞的关系[J].现代康复,1999,3(1):86-8.
38 Minamikawa J,Tanaka S,Yamauch M,et al.Potent inhibtory effect of troglitazone on carotid arterial wall thickness in type 2 diabetes.J Clin Endocrinol Metab 1998,83:1818-1920.
39 Villa,Rabano A,Albarran OG,et al.Effects of chronic combined treatment with captoprdil and pravastain on the progression of insulin resistance and cardiovascular alteration in an experimental model of obesity in dogs Am J Hypertens 1998,11:844-851.
40 Lidahl B,Dinesen B,Eliasson M,et al.High proinsulin levels precede first ever stroke in a nonctiabetic population.Stroke 2000,31(12):2936-2941.
41 刘惠文,张铁志,李光伟,等高血压病患者胰岛素抵抗与中医辨证分型的相关性研究[J].中国中西医结合杂志,1999,19(4):200.
42 蒋卫民,唐蜀华,陈晓虎.高血压病辨证分型与胰岛素抵抗关系的初步研究[J].中国中医基础医学杂志,1998,4(11):37.
43 俞亚琴,王彬.从血瘀角度探讨2型糖尿病胰岛素抵抗[J].浙江中医杂志,2002,(4):175-176.
44 李秋炎,贾太平,赵展荣,等.2型糖尿病患者中医辨证分型与胰岛β细胞功能关系的研究[J].中医杂志,1998,39(7):428.
45 朱章志,熊曼琪.2型糖尿病患者不同证型红细胞胰岛素受体缺陷的观察[J].中国中西医结合杂志,1995,15(5):266-268.
46 周国英,武雪萍,衡先培,等.2型糖尿病气阴两虚证与胰岛素抵抗的相关性研究[J].福建中医药,2000,31(2):7-8.
47 陆灏,丁学屏,蔡淦.84例2型DM辨证分型与胰岛素抵抗、Glucagon的关系[J].辽宁中医杂志,1998,25(9):387-389.
48 丁学屏,陆灏,虞芳华,等.非胰岛素依赖型糖尿病中医辨证分型与胰高糖素、胰岛素敏感性相关研究[J]上海中医药杂志,1999,33(9):18.
49 黎学松,岑永庄,梁干雄,等.2型糖尿病中医分型与胰岛素抵抗相关性分析[J].辽宁中医杂志,1998,25(8):345.
50 孙刚,李晓玲.痰浊证型患者糖、脂等代谢指标检测及其临床意义[J].贵阳中医学院学报,1997,19(3):60.
51 梁兴伦,韩明向.胰岛素抵抗模型大鼠的中医证候研究[J].中国中西医结合杂志,2001,21(7):528-530.
52 吴深涛.对胰岛素抵抗宜用益肾化瘀、疏利少阳[J].中医杂志,2001,42(6):332-333.
53 李道本,王智明 从肝论治防治胰岛素抵抗治疗2型糖尿病的理论探讨 [J].中国中西医结合消化杂志,2001,9(3):153-154.
54 Kim JK,Jae K,and Youn JH.Plasma free fatty acids decrease insulin-stimulated skeletal muscle glucose uptake by suppressing glycolysis in conscious rats.Diabetes,1996,45:446.
55 叶林,吴万龄.胰岛素抵抗治疗的新靶点[J].国外医学.内分泌学分册,2005,(04):76-79.
56 Lee Y,Hirose H,Ohneda M,et al.β-cell lipotoxicity in the pathogenesis of non-insulin dependent diabetes mellitus of obese rats:mpairment in adipocyte-β-cell relationships.Proc Natl Acad Sci USA,1994,91:10878.
57 Moschos S,Chan JL,Mantzoros CS.Leptin and reproduction:a review[J].Fertil Steril,2002,77(3):433.
58 Gabriely I,Ma XH,Yang XM,et al.Leptin resistance during aging is independent of fat mass[J].Diabetes,2002,51(4):1016-1021.
59 Steppan CM,Bailey ST,Bhat S,et al.The hormone resistin links obesity to diabetes[J].Nature,2001,4(6818):307-312.
60 Maeda N,Shimomura I,Kishida K,et al.Dietinducedinsulin resistance in mice lacking adiponectin/ACRP30[J].Nat Med,2002,8(7):731-737.
61 Zeng G,Nystrom FH,Ravichandran LV,et al.Roles for insulin receptor,PI3-kinase,and Akt in insulin-signaling pathways related to production of nitric oxide in human vascular endothelial cells.Circulation.2000,101:1539-1545.
62 Hsueh WA,Law RE.Cardiovascular risk continuum:implication of insulin rasistance and diabetes.Am J Med.1998,105(suppl 1A):4s-14s.
63 华兴邦,李辞蓉,周浩良,等.大鼠穴位图谱的研制[J].实验动物与动物实验,1991,10(1):1-5.
64 Flores-Martinez SE,Islas-Andrade S,Machorro-Lazo MV,et al.DNA polymorphism analysis of candidate genes for type 2 diabetes mellitus in a Mexican ethnic group.Ann Genet,2004 Oct-Dec,47(4):339-348.
65 Algenstaedt P,Hennigs N,Telkamp N,et al.Met326Ile amlnoacid polymorphism in the human p85 alpha gene has no major impact on early insulin signaling in type 2 diabetes.Horm Metab Res.2004 Oct,36(10):686-692.
66 Zorzano A,Fandos C,Palaci M,et al.Role of plasma membrane transporters in muscle metabolism[J].Biochem J,2000,349(3):667-688.
67 Zisman A,Peroni O,Abel E,et al.Targeted disruption of the glucose transporter 04 selectively in muscle causes insulin resistance and glucose intolerance[J].Nat Med,2002,6(8):924-928.
68 Pessin JE,Saltiel AR.Signaling pathways in insulin action:molecular targets of insulin resistance.J Clin Invest.2000,106:165-169.
69 闫妙娥.“痰塞胞宫”生物学基础及其效应(6)—基于卵巢颗粒细胞胰岛素抵抗及其中药干预机制[D].黑龙江中医药大学博士论文,2007:21-36.
70 Julia A,BalfourB,Plosker L.Rosiglitazone[J].Drugs,1999,57(6):921-930.
71 Peraldi P,Spiegelman B.TNF-alpha and insulin resistanceaummary and future prospects[J].Mol Cell Binchem,1998,182(1-2):169-175.
72 Storlien LH,Oakes SD,Pan DA,et al.Syndrome of insulin resistance in the rats:inducement by diet and amelioration with Benfluorex.Diabetes,1993,42:457-462.
73 Coulston AM.The role of dietary fats in plant-based diets.Am J Clin Nutr,1999,70(3 Suppl):512S-515S.
74 Hating HU.Pathogenisisof type 2 diabetes:are there common causesfor insulin resistance and secretion failure.Exp Clin Endocrinol Diabetes,1999,107(suppl 2):s17-s23.
75 Ciaraldi TP,KongASP,Chu NV,et al.Regulationof glucose transport aninsulin signaling by troglitazone or metformin in adipose tissue of type 2 diabetic subjects.Diabetes,2002,51:30-36.
76 FreidJ,Everitt D,Boscia J.Rosiglitazone and hepatic failure.Ann InterMed,2000,132:164.
77 Kazerooni T,Dehqhan-kooshkqhazi M.Effects of metformin therapy on hyperandroqenism in women with polycystic ovarian syndrome.Gynecol Endocrinol,2003,17(1):51.
78 IbanezL,Onq k,Ferrer A,et al.low dose flutamide-metformin therapy reverses insulin resistance and reduces fat mass in nonobese adoles-cents with ovarian hyperandroqenism.J Clin Endocrinol Metab,2003,88(6):2600.
79 Passsquali R,Gambineri A,Biscotti D,et al.Effect of long-term treatment with metformin added to hypocaloric diet on body composition,fat distribution,andd androgen and insulin levels in abdominally obese women with and without the polycystic ovarian syndrome.J of Clin Endocri and Metab,2000(85)2767-2774.
80 吴启端,熊曼琪,方永奇,等.一次性腹腔注射链佐霉素制备大鼠糖尿病模型[J].中药新药与临床药理,1998,9(1):37-38.
81 于德民,吴锐,尹潍,等.实验性链脉佐菌素糖尿病动物模型的研究[J].中国糖尿病杂志,1995,3(2):105-109.
82 李晨钟.胰岛素抵抗的动物模型[J].国外医学·内分泌学分册,1998,18(3):144-147.
83 于丽萍,张雪,王玉芝,等.单剂卷柏对FFR胰岛素敏感性的影响[J].中成药,2001,23(4):291-292.
84 Storlien LH,James DE,Burleigb KM,et al.Fat feeding causes widespread in vivo insulin resistance,decreased energy expenditure,and obesity in rats.Am,J Pbysiol,1986,25(Endodrinol,Metab14):E576-E583.
85 王桂珍,黄小明,陈秀芳,等.月见草油和多烯康对糖尿病大鼠胰岛素抵抗的治疗作用[J].浙江医学,1998,20(1):24-25.
86 鲁瑾,邹大进,张家庆,等.黄芪预防肿瘤坏死因子-α所致胰岛素抵抗[J].中国中西医结合杂志,1999,19(7):420-422.
87 李晨钟,张素华,舒昌达,等.用高脂肪膳食复制胰岛素抵抗大鼠模型[J].基础医学与临床,2000,20(3):93-95.
88 东富云,曹又陵,汤新之.高蔗糖膳食诱发大鼠胰岛素抵抗的研究[J].实验动物科学与管理,1998,15(4):1-4.
89 Kawano K et at.Spontaneous Long-term hyperglycemic rat with diabetic com(?)lications-Ostaka Long-Evanx Tokushima Fatty(OLETF)strain.Diabetes,1992,41:14-22.
990 赵晓华,宋征,李兴,等.胰岛素抵抗性非胰岛素依赖型糖尿病大鼠模型研制[J].中华预防医学杂志,1999,33(5):300-303
991 熊曼琪,林安钟,朱章志,等.加味桃核承气汤对Ⅱ型糖尿病大鼠胰岛素抵抗的影响[J].中国中西医结合杂志,1997,17(3):165-168.
992 朱章志,熊曼琪,林安钟,等.三黄降糖方对Ⅱ型糖尿病患者外周胰岛素抵抗的影响[J].中国中西医结合杂志,1997,17(10):590-593.
993 李赛美,熊曼琪,林安钟,等.不同治法阻断糖尿病大鼠高糖、高脂、胰岛素抵抗的初步观察[J].中国中医基础医学杂志,1999,5(8):28.
994 薛军,罗小星,陈镜合.中药对糖尿病大鼠心肌缺血及胰岛素水平的影响[J].中国中医急症,1998,7(6):269-271.
995 申竹芳,谢明智,刘海帆.金茂降糖片对实验动物血脂、胰岛素抗性及免疫功能的影响[J].中药新药与临床药理,1997,8(1):23.
996 梁兴伦,韩明向,周宜轩,等.四安胶囊对X综合征治疗效应的实验研究[J].中国实验方剂学杂志,1999,5(1):39-40.
997 杨化冰,欧阳静萍.复方降糖液对2型糖尿病大鼠血糖及血清TNF-α、PA1-1作用的研究[J].湖北中医杂志,2001,23(12):9-10.
998 王凌,李秋贵,浦信行,等.参地降糖颗粒对高果糖大鼠胰岛素抵抗的影响[J].中医杂志,2001,42(11):686-688.
999 王作成,曲竹秋.糖尿停对非胰岛素依赖型糖尿病大鼠糖、脂代谢及胰岛素分泌的影响[J].天津中医,1998,15(3):128-130.
1000 陆灏,朱宇清,唐静芬,等.三黄煎对2型糖尿病大鼠胰岛素分泌功能的影响[J].辽宁中医药杂志,2000,27(6):281-283.
1001 李怡,李秋贵,常志彦,等.不同剂量糖肾胶囊对FFR胰岛素敏感性的影响[J].中国医药学报,1999,14(3):15-17.
1002 黄平,杨明华,顾维正,等.养阴降糖片治疗糖尿病大鼠高黏滞血症的实验研究[J].中国中医药科技,2001,8(6):349-351.
1003 刘志诚,孙凤岷,韩燕,等.针刺治疗单纯性肥胖症的实验研究[J].针刺研究,1998,23(1):69-75.
104 刘志诚,沈梅红,魏群利,等.针灸对单纯性肥胖症胰岛素抵抗的作用.江苏中医,1999年专辑:8.
105 刘志诚,孙凤岷,马志民,等.针刺对非胰岛素依赖性糖尿病大鼠渴中枢的作用[J].中国针灸,2002,22(2):121-124.
106 刘志诚,孙凤岷,袁锦虹,等.针刺对非胰岛素依赖性糖尿病大鼠下丘脑外侧区的作用[J].中国中医基础医学杂志,2001,7(9):32-35.
107 刘志诚,项晓人,袁锦虹,等.针刺对NIDDM大鼠作用的形态学观察[J].现代中西医结合杂志,2002,11(17):1650-1652.
108 方水林,钱琪,谢银芳,等.自制消渴颗粒剂配合糖尿病治疗仪治疗2型糖尿病临床观察[J].安徽中医临床杂志,2002,14(3):184-185.
109 袁兴顺,刘文勇,丁学屏,等.补肾强身功对2型糖尿病胰岛素抵抗的影响[J].上海中医药杂志,1999,(11):37-38.
110 易玮.针刺对胰岛素抵抗干预作用的研究[D].广州中医药大学博士论文,2002.
111 曹少鸣.针灸治疗NIDDM大鼠的实验研究[J].上海针灸杂志,1997,16(5):28.
112[日]加藤麦.电针刺激对糖尿病大鼠胰岛素抵抗的影响[J].国外医学.中医中药分册,2001;23(1):47.
113 郑惠田译.手阳明大肠经和胰岛素分泌[J].上海针灸杂志.1993,12(1):43.
114 葛子,王少宁,张国玺,等.针刺对下丘脑内与糖代谢等有关酶的影响[J].中国针灸,1984,4(6):31.
115 杨善军.针刺夹脊穴对防治大鼠胰岛素抵抗作用机制的研究[D].黑龙江中医药大学硕士论文,2007.
116 周逸平,王月兰,汪克明,等.针刺心经经脉对自发性高血压大鼠血压及生化指标的影响[J].中国中医药科技,1996,3(6):6-8.
117 许能贵,梁兴伦.针刺对自发性高血压大鼠血压及胰岛素抵抗的效应研究[J].中国针灸,1997,17(8):493-496.
118 谌剑飞,马雅玲,丁萍,等.针刺对2型糖尿病患者免疫细胞因子、胰岛素敏感指数及血凝指标的影响[J].JTCM.Jan,2002,43(1):30-32.
119 谌剑飞,马雅玲,蔡绍华,等.针刺对糖尿病的抗凝与逆转胰岛素抵抗作用[J].上海针灸杂志,2001,20(4):5-7.
120 魏群利,刘志诚.针刺配合耳穴压籽治疗2型糖尿病(肥胖型)67例[J].安徽中医学院学报2002,21(3):34-37.
121 熊光轶,汗春,欧阳宏.针刺对2型糖尿病胰岛素敏感指数的影响[J].云南中医学院学报,2001,24(3):38-39.
122 秦福兰,贾杰,郭学军.针刺和运动疗法对2型糖尿病的疗效观察[J].中国针灸,2002,22(9):579-581.
123 刘志诚,孙风岷,朱苗花,等.针灸对非胰岛素依赖性糖尿病胰岛素抵抗的影响[J].上海针灸杂志,2000,19(1):5-7.
124 张智龙,薛 莉,吉学群,等.针刺对2型糖尿病胰岛素抵抗影响的临床研[J].中国针灸,2002,22(11):723-725.
125 胡葵,李嘉.针灸治疗肥胖型NIDDM的临床研究[J].上海针灸杂志,2001,20(4):8-9.
126 李嘉,袁锦虹.针灸治疗非胰岛素依赖型糖尿病肥胖型的临床观察及作用机理研究[D].南京中医药大学硕士论文 2000.
127 唐胜修.头穴对中风后遗症患者胰岛素抵抗的调整作用研究[J].安徽中医临床杂志,2002,14(3):164-165.
128 姜岳波.脑梗死针刺治疗方案的优选及对IR的影响[D].黑龙江中医药大学硕士论文,2006.
129 Rattigan S,Filscll OH,Reppucci D,et al.Impaired basal and epinephrine-stimulated glucose uptake by hearts from rats fed high-fat diets[J].Nutr Rep Int,1983,28:603-612.
130 Hissin PJ,Karniele E,Simpson IA,et al.A possible mechanism of insulin resistance in the rat adipose cell with high-fat/low-carbohydrate feeding.Depletion of intracellular glucose transport systems[J].Diates,1982,31:589-592.
131 Ye,JM,Doyle PJ,Iglesias MA,et al.Peroxisome proliferator-activated receptor(PPAR)-alpha activation lowers muscle lipids and improves insulin sensitivity in high fat-fed rats:comparison with PPAR-gamma acaivation[J].Diabetes,2001,50(2):411-417.
132 Mannucci E,Bardini G,Ognibene A,et al.Comparison between 2 insulin sensitivity indexcs in obese patients[J].Diabetes Care,2000,23(7):1042-1043.
133 Kelley DE,Mandarino LJ.Fuel selection in human skeletal muscle in insulin resistance:a reexamination[J].Diabetes,2000,49(5):677-683.
134 李芳萍.胰岛素抵抗体内检测方法[J].国外医学·内科学分册,1998,25(3):108-111.
135 Reaven GM.Role of Insulin Resistance in Human Disease (Syndrome X):An Expanded Definition.Annu Rev Med,1993,44:121-131.
136 周衍椒,张镜如.生理学.人民卫生出版社.1978:468-470.
137 超楚生,廖二元.激素不敏感综合征:湖南科学技术出版社.1998:12-74.
138 Shewan AM et al.Potential role of kinase B in insulin-induced glucose inlucose transport,giycogen synthesis,and protein synthesis.Biochem J,2000;350 Pt 1:99
139 唐万欣,黄颂敏.胰岛素刺激葡萄糖转运蛋白4易位的信号传导机制[J].国外医学分子生物学分册,2003,25(1)26-9.
140 Bodine SC,Stitt TN,Gonzalez M,et al.Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo.Nat Cell Biol,2001,3(11):1014-1019.
141 唐强.头针结合易化技术对脑卒中患者运动功能影响[J].中国康复理论与实践,2001,7(2):71-74.
142 Pessin JE,Salticl AR.Signaling pathways in insulin action:molecular targets of insulins of resistance.J Clin Invest.2000,106:165-169
143 Oku A,Nawano M,Ueta K et al.Inhibitory effect of hyperglyce-mia on insulin-induced Akt/protein kinase B activation in skeletal muscle.Amerieiaa Journal of Physiology-Endocrinology and Metabolism,2001,280(5):E816-824.
144 Smith U,Axelsen M,Carvalho E.Elasson B et al.Insulin signaling and action in fat cells:Associations with insulin resistance and type 2diahetes.Annals of the New York Academy of Sciences,1999,92(10):119-126.
145 Kim Y B,Peroni O D,Franke T F et al.Divergent regulalion of Akt1 and Akt2 isoforms in insulin target tissues of obese Zncker rats.Diabetes,2000,49(5):847-856.
146 Tremblav F,Lavigne C,Jacques H et al.Dietry cod protein resores insulin-induceded activaion of phosphatidvlionsitol 3-kinase/Akt and Glut4 translocation to the T-tubules in skeletall muscle of high fat-feel obese rats.Diabetes,2003,52(1):29-37.
147 Kansch C,Krutzfeldt J,Wilke A et al.Effecas of troglilazone on cellular differentiation,insulin signaling and glucose melaholism in cultured human skeletal muscle cells.Biochemical and Biophysical Research communication,2001,280(3):264-267.
148 Ueki K,Yamamoto R,Kahurani Y,et al.Potential role of kinase B in insulin-induced glucose inlucose transport,glycogen synthesis,and protein synthesis.J Biol,Chem,1998,273(9):5315-5322.
149 Cho H,Mu J,Kim Jk,et al.Insulin resistance and a diabetes mellitus-like syndrome in mice lackinn the protein kinase Akt2(PKB beta).Science,2001,292:1728-1731.
150 Schmilz Peiffcr C.Signaling aspecas of insulin resistance in skeletal muscle:mechanisms induced by lipid oversupply.Cellular Signalling,2000,12(9-10):583-594.
151 任婷婷,杨建梅.胰岛素对葡萄糖摄取的调节:细胞内信号通路复杂的相互作用[J].中国糖尿病杂志,2003,11(4):303-304.
152 冯美江,丁新生.Akt与细胞生存[J].国外医学分子生物学分册,2002,24(5):283-285
153 邹伟,李兆育,李春蕾等.蛋白激酶B及其在磷脂酰肌醇3—激酶介导的信号转导中的作用[J].生理科学进展,2000,31(2):120-124.
154 Ilcen L Whileman,Han Cbo,Morris J,Birnbanm.Role of Akt/protein kinasc B in metabolism.Treads is Eadocriadogy and Metabolism,2002,13(12):444-451.
155 马通军,尹潍.TNF-α致胰岛素抵抗的机制[J].国外医学.内分泌学分册,2000,(02).
156 张艳珍,李创鹏,马雅珍,等.针刺治疗急性脑梗死对TNF-a,IL-6及肌力的影响.中国针灸,2001,21(11):677.
2 姜欣荣,邓浩萍.胰岛素抵抗与相关疾病[J].医学综述,1998,4(9):500-501.
3 李秀钧,胰岛素抵抗综合征,人民卫生出版社.2001.
4 杨丽娟.胰岛素抵抗及其临床处理[J].现代康复,2000,4(5):760.
5 Reaven GM,Role of insulin resistance in human disease.Diabetes,1988,37(12):1595.
6 WHO.Definition,Diagnosis and classification of Diabetes Mellitus and its Complications.Report of a WHO Consultation,1999,31-34.
7 Bloomgaren ZT.American Diabetes Association annual meeting,insulin rasistance,esercise and obesxity.Diabetes Care,1999,22:517-522.
8 Jia WP,Xiang KS,Chen L,et al.Epidemiologic study on metabolic syndrome in mormal and overweight Chinese in Shanghai.Diabetes,2000(snppl 1)49:A184.
9 李秀钧.胰岛素抵抗及胰岛素抵抗综合征研究展望[J].中华内分泌代谢杂志,2000,16(5):274-276.
10 Festa A,D Agostino R,Jr,Mykkanen L.LDL particle size in relalion to insulin,proinsnlin,and insulin sensitivity.The Insulin Resistance Atherosderosis Study.Diabetes Care,1999,22:1688-1693.
11 Groop LC.Insulin resistance:the fundamentatl trigger of type 2 diabetes mellitus.Obesity & Metabolism.1999,1:2-9.
12 程歆琦,鄢盛恺,宋耀虹.代谢综合征与血脂异常[J].国外医学.临床生物化学与检验学分册,2005,(02):102.
13 Alberti KGMM,Zimmet PZ for the WHO consultation.Definition,diagnosis and classification of diabetes mellitus and its complications-part 1:diagnosis and classification of diabetes mellitus provisional report of a who consultation.Diabetic Medicine,1998,539-553.
14 Shinozaki K,Naritomi H,Shimizu T,et al.Role of insulin resistanceassociated with compenosatory hypewinsulinemia in ischemic stroke.Strok 1996,27:37-43.
15 Lindahl B,Dinesen B,Eliasson M,et al.High proinsulin levels precede first-ever stroke in a nondiabetic population.Stroke 2000,31:2936-2941.
16 KuusistoJ,Mykkanen L,Pyorala K,et al.Non-insulin-dependent diabetes and its metabolic control are important predirtors of stroke in elderly subjects.Strok 1994,25:1157-1164.
17 Wanamethee SC,Perry IJ,Shaper AG.Nonfasting serum glucose and insulin concentrations and the risk of stroke.Strok 1999,30:1780-1786.
18 Lakka HM,Lakka TA,Tuomilehtom J,et al.Hyoerinsulinemia and the risk of cardiovascular death and acute coronary and cerebrovascular evens in men.Arch Intern Med 2000,160:1160-1168.
19 Pyoeala M,Miettinen H,Laakso M,et al.Hyperinsulinemia and the risk of stroke in healthy middle aged men.The 22 year follow-up results of the Helsinki policemen study.Strok 1998,29:1860-1866.
20 Folsom AR,Rasmussen ML,Chambless LK,et al.Prospective associations of fasting insulin body fat distribution and diabetes with risk of ischemic stroke.Diabetes Care 1999,22:1077-1083.
21 邹立,彭凯润,张幸运.胰岛素抵抗与脑梗死关系的研究[J].临床神经病学杂志,1996,9:152.
22 何丽彬,周旭光,孙伟峰,等.胰岛素抵抗及其与缺血性脑血管病关系的研究[J]黑龙江医学,2001,25(3):165-167.
23 Yalow R,Berson SA.Immunoassay of endogenous plasma insulin in man.J Clin Invest.1960,39:1157-1175.
24 李光伟.胰岛素敏感性评估及其在临床研究中的应用[J].中华内分泌代谢杂志,2000,16(3):198-200.
25 Bergman RN,Finegood DT,Ader M.Assessment of insulin sensitivity in vivo.EndocrRev.1985,6(1):45-86.
26 张家庆.新的HOMA-IR—从空腹血糖、空腹胰岛素测胰岛素抵抗[J].中 华糖尿病杂志,2005,3(4):245-246.
27 李光伟,潘孝仁,Stephen Lillioja,et al.检测人群胰岛素敏感性的一项新指数[J].中华内科杂志,1993,32(10):656-660.
28 陈为安.胰岛素抵抗、血脂异常与急性脑梗死关系的初步研究[D].苏州大学硕士论文,2002:15-18.
29 都健,赵玉岩,谢辉,等.喂养型胰岛素抵抗动物模型的建立与评价[J].中国医科大学学报,2002,31(5)343-346.
30 Scherrer U,Sartori C.Insulin as a vascular and sympathoex-citatory hormone.Lmplication for blood pressure regulation,insulin sensitivity,and cardiovascular morbidity.Circulation,1997,96:4101-4113.
31 Bonora E,Willeit J,Kiechl S,et al.Relationship between insulin and carotid atherosclerosis in the general population[J].Stroke,1997,28:1147.
32 黄海泉.胰岛素抵抗与动脉粥样硬化[J]临床荟萃,2005,(13):45.
33 Byberg L,Siegbahn A,Berglund L,et al.Plasminogen activator unhibitor activity is independently relared to both insulin sensrtivity and serum triglycerides in 70-year old men.Arterioselerosis 1998,18(2):258-264.
34 柳太云.胰岛素抵抗、高脂血症与缺血.性脑卒中[J].临床神经病学杂志,1999,12(1):32-33.
35 张熙泉,商淑梅,梁继舜,等.胰岛素抵抗与高血压性脑出血关系初步探讨[J].中国神经免疫和神经病学杂志,1999,6(1):36-40.
36 王振才,陈晓红,张建宏,等.胰岛素抵抗与正常血压脑出血及脑梗塞关系的探讨[J].脑与神经疾病杂志,1998,6(3):135-137.
37 旃培艳,张临洪.胰岛素抵抗与糖尿病腔隙性梗塞的关系[J].现代康复,1999,3(1):86-8.
38 Minamikawa J,Tanaka S,Yamauch M,et al.Potent inhibtory effect of troglitazone on carotid arterial wall thickness in type 2 diabetes.J Clin Endocrinol Metab 1998,83:1818-1920.
39 Villa,Rabano A,Albarran OG,et al.Effects of chronic combined treatment with captoprdil and pravastain on the progression of insulin resistance and cardiovascular alteration in an experimental model of obesity in dogs Am J Hypertens 1998,11:844-851.
40 Lidahl B,Dinesen B,Eliasson M,et al.High proinsulin levels precede first ever stroke in a nonctiabetic population.Stroke 2000,31(12):2936-2941.
41 刘惠文,张铁志,李光伟,等高血压病患者胰岛素抵抗与中医辨证分型的相关性研究[J].中国中西医结合杂志,1999,19(4):200.
42 蒋卫民,唐蜀华,陈晓虎.高血压病辨证分型与胰岛素抵抗关系的初步研究[J].中国中医基础医学杂志,1998,4(11):37.
43 俞亚琴,王彬.从血瘀角度探讨2型糖尿病胰岛素抵抗[J].浙江中医杂志,2002,(4):175-176.
44 李秋炎,贾太平,赵展荣,等.2型糖尿病患者中医辨证分型与胰岛β细胞功能关系的研究[J].中医杂志,1998,39(7):428.
45 朱章志,熊曼琪.2型糖尿病患者不同证型红细胞胰岛素受体缺陷的观察[J].中国中西医结合杂志,1995,15(5):266-268.
46 周国英,武雪萍,衡先培,等.2型糖尿病气阴两虚证与胰岛素抵抗的相关性研究[J].福建中医药,2000,31(2):7-8.
47 陆灏,丁学屏,蔡淦.84例2型DM辨证分型与胰岛素抵抗、Glucagon的关系[J].辽宁中医杂志,1998,25(9):387-389.
48 丁学屏,陆灏,虞芳华,等.非胰岛素依赖型糖尿病中医辨证分型与胰高糖素、胰岛素敏感性相关研究[J]上海中医药杂志,1999,33(9):18.
49 黎学松,岑永庄,梁干雄,等.2型糖尿病中医分型与胰岛素抵抗相关性分析[J].辽宁中医杂志,1998,25(8):345.
50 孙刚,李晓玲.痰浊证型患者糖、脂等代谢指标检测及其临床意义[J].贵阳中医学院学报,1997,19(3):60.
51 梁兴伦,韩明向.胰岛素抵抗模型大鼠的中医证候研究[J].中国中西医结合杂志,2001,21(7):528-530.
52 吴深涛.对胰岛素抵抗宜用益肾化瘀、疏利少阳[J].中医杂志,2001,42(6):332-333.
53 李道本,王智明 从肝论治防治胰岛素抵抗治疗2型糖尿病的理论探讨 [J].中国中西医结合消化杂志,2001,9(3):153-154.
54 Kim JK,Jae K,and Youn JH.Plasma free fatty acids decrease insulin-stimulated skeletal muscle glucose uptake by suppressing glycolysis in conscious rats.Diabetes,1996,45:446.
55 叶林,吴万龄.胰岛素抵抗治疗的新靶点[J].国外医学.内分泌学分册,2005,(04):76-79.
56 Lee Y,Hirose H,Ohneda M,et al.β-cell lipotoxicity in the pathogenesis of non-insulin dependent diabetes mellitus of obese rats:mpairment in adipocyte-β-cell relationships.Proc Natl Acad Sci USA,1994,91:10878.
57 Moschos S,Chan JL,Mantzoros CS.Leptin and reproduction:a review[J].Fertil Steril,2002,77(3):433.
58 Gabriely I,Ma XH,Yang XM,et al.Leptin resistance during aging is independent of fat mass[J].Diabetes,2002,51(4):1016-1021.
59 Steppan CM,Bailey ST,Bhat S,et al.The hormone resistin links obesity to diabetes[J].Nature,2001,4(6818):307-312.
60 Maeda N,Shimomura I,Kishida K,et al.Dietinducedinsulin resistance in mice lacking adiponectin/ACRP30[J].Nat Med,2002,8(7):731-737.
61 Zeng G,Nystrom FH,Ravichandran LV,et al.Roles for insulin receptor,PI3-kinase,and Akt in insulin-signaling pathways related to production of nitric oxide in human vascular endothelial cells.Circulation.2000,101:1539-1545.
62 Hsueh WA,Law RE.Cardiovascular risk continuum:implication of insulin rasistance and diabetes.Am J Med.1998,105(suppl 1A):4s-14s.
63 华兴邦,李辞蓉,周浩良,等.大鼠穴位图谱的研制[J].实验动物与动物实验,1991,10(1):1-5.
64 Flores-Martinez SE,Islas-Andrade S,Machorro-Lazo MV,et al.DNA polymorphism analysis of candidate genes for type 2 diabetes mellitus in a Mexican ethnic group.Ann Genet,2004 Oct-Dec,47(4):339-348.
65 Algenstaedt P,Hennigs N,Telkamp N,et al.Met326Ile amlnoacid polymorphism in the human p85 alpha gene has no major impact on early insulin signaling in type 2 diabetes.Horm Metab Res.2004 Oct,36(10):686-692.
66 Zorzano A,Fandos C,Palaci M,et al.Role of plasma membrane transporters in muscle metabolism[J].Biochem J,2000,349(3):667-688.
67 Zisman A,Peroni O,Abel E,et al.Targeted disruption of the glucose transporter 04 selectively in muscle causes insulin resistance and glucose intolerance[J].Nat Med,2002,6(8):924-928.
68 Pessin JE,Saltiel AR.Signaling pathways in insulin action:molecular targets of insulin resistance.J Clin Invest.2000,106:165-169.
69 闫妙娥.“痰塞胞宫”生物学基础及其效应(6)—基于卵巢颗粒细胞胰岛素抵抗及其中药干预机制[D].黑龙江中医药大学博士论文,2007:21-36.
70 Julia A,BalfourB,Plosker L.Rosiglitazone[J].Drugs,1999,57(6):921-930.
71 Peraldi P,Spiegelman B.TNF-alpha and insulin resistanceaummary and future prospects[J].Mol Cell Binchem,1998,182(1-2):169-175.
72 Storlien LH,Oakes SD,Pan DA,et al.Syndrome of insulin resistance in the rats:inducement by diet and amelioration with Benfluorex.Diabetes,1993,42:457-462.
73 Coulston AM.The role of dietary fats in plant-based diets.Am J Clin Nutr,1999,70(3 Suppl):512S-515S.
74 Hating HU.Pathogenisisof type 2 diabetes:are there common causesfor insulin resistance and secretion failure.Exp Clin Endocrinol Diabetes,1999,107(suppl 2):s17-s23.
75 Ciaraldi TP,KongASP,Chu NV,et al.Regulationof glucose transport aninsulin signaling by troglitazone or metformin in adipose tissue of type 2 diabetic subjects.Diabetes,2002,51:30-36.
76 FreidJ,Everitt D,Boscia J.Rosiglitazone and hepatic failure.Ann InterMed,2000,132:164.
77 Kazerooni T,Dehqhan-kooshkqhazi M.Effects of metformin therapy on hyperandroqenism in women with polycystic ovarian syndrome.Gynecol Endocrinol,2003,17(1):51.
78 IbanezL,Onq k,Ferrer A,et al.low dose flutamide-metformin therapy reverses insulin resistance and reduces fat mass in nonobese adoles-cents with ovarian hyperandroqenism.J Clin Endocrinol Metab,2003,88(6):2600.
79 Passsquali R,Gambineri A,Biscotti D,et al.Effect of long-term treatment with metformin added to hypocaloric diet on body composition,fat distribution,andd androgen and insulin levels in abdominally obese women with and without the polycystic ovarian syndrome.J of Clin Endocri and Metab,2000(85)2767-2774.
80 吴启端,熊曼琪,方永奇,等.一次性腹腔注射链佐霉素制备大鼠糖尿病模型[J].中药新药与临床药理,1998,9(1):37-38.
81 于德民,吴锐,尹潍,等.实验性链脉佐菌素糖尿病动物模型的研究[J].中国糖尿病杂志,1995,3(2):105-109.
82 李晨钟.胰岛素抵抗的动物模型[J].国外医学·内分泌学分册,1998,18(3):144-147.
83 于丽萍,张雪,王玉芝,等.单剂卷柏对FFR胰岛素敏感性的影响[J].中成药,2001,23(4):291-292.
84 Storlien LH,James DE,Burleigb KM,et al.Fat feeding causes widespread in vivo insulin resistance,decreased energy expenditure,and obesity in rats.Am,J Pbysiol,1986,25(Endodrinol,Metab14):E576-E583.
85 王桂珍,黄小明,陈秀芳,等.月见草油和多烯康对糖尿病大鼠胰岛素抵抗的治疗作用[J].浙江医学,1998,20(1):24-25.
86 鲁瑾,邹大进,张家庆,等.黄芪预防肿瘤坏死因子-α所致胰岛素抵抗[J].中国中西医结合杂志,1999,19(7):420-422.
87 李晨钟,张素华,舒昌达,等.用高脂肪膳食复制胰岛素抵抗大鼠模型[J].基础医学与临床,2000,20(3):93-95.
88 东富云,曹又陵,汤新之.高蔗糖膳食诱发大鼠胰岛素抵抗的研究[J].实验动物科学与管理,1998,15(4):1-4.
89 Kawano K et at.Spontaneous Long-term hyperglycemic rat with diabetic com(?)lications-Ostaka Long-Evanx Tokushima Fatty(OLETF)strain.Diabetes,1992,41:14-22.
990 赵晓华,宋征,李兴,等.胰岛素抵抗性非胰岛素依赖型糖尿病大鼠模型研制[J].中华预防医学杂志,1999,33(5):300-303
991 熊曼琪,林安钟,朱章志,等.加味桃核承气汤对Ⅱ型糖尿病大鼠胰岛素抵抗的影响[J].中国中西医结合杂志,1997,17(3):165-168.
992 朱章志,熊曼琪,林安钟,等.三黄降糖方对Ⅱ型糖尿病患者外周胰岛素抵抗的影响[J].中国中西医结合杂志,1997,17(10):590-593.
993 李赛美,熊曼琪,林安钟,等.不同治法阻断糖尿病大鼠高糖、高脂、胰岛素抵抗的初步观察[J].中国中医基础医学杂志,1999,5(8):28.
994 薛军,罗小星,陈镜合.中药对糖尿病大鼠心肌缺血及胰岛素水平的影响[J].中国中医急症,1998,7(6):269-271.
995 申竹芳,谢明智,刘海帆.金茂降糖片对实验动物血脂、胰岛素抗性及免疫功能的影响[J].中药新药与临床药理,1997,8(1):23.
996 梁兴伦,韩明向,周宜轩,等.四安胶囊对X综合征治疗效应的实验研究[J].中国实验方剂学杂志,1999,5(1):39-40.
997 杨化冰,欧阳静萍.复方降糖液对2型糖尿病大鼠血糖及血清TNF-α、PA1-1作用的研究[J].湖北中医杂志,2001,23(12):9-10.
998 王凌,李秋贵,浦信行,等.参地降糖颗粒对高果糖大鼠胰岛素抵抗的影响[J].中医杂志,2001,42(11):686-688.
999 王作成,曲竹秋.糖尿停对非胰岛素依赖型糖尿病大鼠糖、脂代谢及胰岛素分泌的影响[J].天津中医,1998,15(3):128-130.
1000 陆灏,朱宇清,唐静芬,等.三黄煎对2型糖尿病大鼠胰岛素分泌功能的影响[J].辽宁中医药杂志,2000,27(6):281-283.
1001 李怡,李秋贵,常志彦,等.不同剂量糖肾胶囊对FFR胰岛素敏感性的影响[J].中国医药学报,1999,14(3):15-17.
1002 黄平,杨明华,顾维正,等.养阴降糖片治疗糖尿病大鼠高黏滞血症的实验研究[J].中国中医药科技,2001,8(6):349-351.
1003 刘志诚,孙凤岷,韩燕,等.针刺治疗单纯性肥胖症的实验研究[J].针刺研究,1998,23(1):69-75.
104 刘志诚,沈梅红,魏群利,等.针灸对单纯性肥胖症胰岛素抵抗的作用.江苏中医,1999年专辑:8.
105 刘志诚,孙凤岷,马志民,等.针刺对非胰岛素依赖性糖尿病大鼠渴中枢的作用[J].中国针灸,2002,22(2):121-124.
106 刘志诚,孙凤岷,袁锦虹,等.针刺对非胰岛素依赖性糖尿病大鼠下丘脑外侧区的作用[J].中国中医基础医学杂志,2001,7(9):32-35.
107 刘志诚,项晓人,袁锦虹,等.针刺对NIDDM大鼠作用的形态学观察[J].现代中西医结合杂志,2002,11(17):1650-1652.
108 方水林,钱琪,谢银芳,等.自制消渴颗粒剂配合糖尿病治疗仪治疗2型糖尿病临床观察[J].安徽中医临床杂志,2002,14(3):184-185.
109 袁兴顺,刘文勇,丁学屏,等.补肾强身功对2型糖尿病胰岛素抵抗的影响[J].上海中医药杂志,1999,(11):37-38.
110 易玮.针刺对胰岛素抵抗干预作用的研究[D].广州中医药大学博士论文,2002.
111 曹少鸣.针灸治疗NIDDM大鼠的实验研究[J].上海针灸杂志,1997,16(5):28.
112[日]加藤麦.电针刺激对糖尿病大鼠胰岛素抵抗的影响[J].国外医学.中医中药分册,2001;23(1):47.
113 郑惠田译.手阳明大肠经和胰岛素分泌[J].上海针灸杂志.1993,12(1):43.
114 葛子,王少宁,张国玺,等.针刺对下丘脑内与糖代谢等有关酶的影响[J].中国针灸,1984,4(6):31.
115 杨善军.针刺夹脊穴对防治大鼠胰岛素抵抗作用机制的研究[D].黑龙江中医药大学硕士论文,2007.
116 周逸平,王月兰,汪克明,等.针刺心经经脉对自发性高血压大鼠血压及生化指标的影响[J].中国中医药科技,1996,3(6):6-8.
117 许能贵,梁兴伦.针刺对自发性高血压大鼠血压及胰岛素抵抗的效应研究[J].中国针灸,1997,17(8):493-496.
118 谌剑飞,马雅玲,丁萍,等.针刺对2型糖尿病患者免疫细胞因子、胰岛素敏感指数及血凝指标的影响[J].JTCM.Jan,2002,43(1):30-32.
119 谌剑飞,马雅玲,蔡绍华,等.针刺对糖尿病的抗凝与逆转胰岛素抵抗作用[J].上海针灸杂志,2001,20(4):5-7.
120 魏群利,刘志诚.针刺配合耳穴压籽治疗2型糖尿病(肥胖型)67例[J].安徽中医学院学报2002,21(3):34-37.
121 熊光轶,汗春,欧阳宏.针刺对2型糖尿病胰岛素敏感指数的影响[J].云南中医学院学报,2001,24(3):38-39.
122 秦福兰,贾杰,郭学军.针刺和运动疗法对2型糖尿病的疗效观察[J].中国针灸,2002,22(9):579-581.
123 刘志诚,孙风岷,朱苗花,等.针灸对非胰岛素依赖性糖尿病胰岛素抵抗的影响[J].上海针灸杂志,2000,19(1):5-7.
124 张智龙,薛 莉,吉学群,等.针刺对2型糖尿病胰岛素抵抗影响的临床研[J].中国针灸,2002,22(11):723-725.
125 胡葵,李嘉.针灸治疗肥胖型NIDDM的临床研究[J].上海针灸杂志,2001,20(4):8-9.
126 李嘉,袁锦虹.针灸治疗非胰岛素依赖型糖尿病肥胖型的临床观察及作用机理研究[D].南京中医药大学硕士论文 2000.
127 唐胜修.头穴对中风后遗症患者胰岛素抵抗的调整作用研究[J].安徽中医临床杂志,2002,14(3):164-165.
128 姜岳波.脑梗死针刺治疗方案的优选及对IR的影响[D].黑龙江中医药大学硕士论文,2006.
129 Rattigan S,Filscll OH,Reppucci D,et al.Impaired basal and epinephrine-stimulated glucose uptake by hearts from rats fed high-fat diets[J].Nutr Rep Int,1983,28:603-612.
130 Hissin PJ,Karniele E,Simpson IA,et al.A possible mechanism of insulin resistance in the rat adipose cell with high-fat/low-carbohydrate feeding.Depletion of intracellular glucose transport systems[J].Diates,1982,31:589-592.
131 Ye,JM,Doyle PJ,Iglesias MA,et al.Peroxisome proliferator-activated receptor(PPAR)-alpha activation lowers muscle lipids and improves insulin sensitivity in high fat-fed rats:comparison with PPAR-gamma acaivation[J].Diabetes,2001,50(2):411-417.
132 Mannucci E,Bardini G,Ognibene A,et al.Comparison between 2 insulin sensitivity indexcs in obese patients[J].Diabetes Care,2000,23(7):1042-1043.
133 Kelley DE,Mandarino LJ.Fuel selection in human skeletal muscle in insulin resistance:a reexamination[J].Diabetes,2000,49(5):677-683.
134 李芳萍.胰岛素抵抗体内检测方法[J].国外医学·内科学分册,1998,25(3):108-111.
135 Reaven GM.Role of Insulin Resistance in Human Disease (Syndrome X):An Expanded Definition.Annu Rev Med,1993,44:121-131.
136 周衍椒,张镜如.生理学.人民卫生出版社.1978:468-470.
137 超楚生,廖二元.激素不敏感综合征:湖南科学技术出版社.1998:12-74.
138 Shewan AM et al.Potential role of kinase B in insulin-induced glucose inlucose transport,giycogen synthesis,and protein synthesis.Biochem J,2000;350 Pt 1:99
139 唐万欣,黄颂敏.胰岛素刺激葡萄糖转运蛋白4易位的信号传导机制[J].国外医学分子生物学分册,2003,25(1)26-9.
140 Bodine SC,Stitt TN,Gonzalez M,et al.Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo.Nat Cell Biol,2001,3(11):1014-1019.
141 唐强.头针结合易化技术对脑卒中患者运动功能影响[J].中国康复理论与实践,2001,7(2):71-74.
142 Pessin JE,Salticl AR.Signaling pathways in insulin action:molecular targets of insulins of resistance.J Clin Invest.2000,106:165-169
143 Oku A,Nawano M,Ueta K et al.Inhibitory effect of hyperglyce-mia on insulin-induced Akt/protein kinase B activation in skeletal muscle.Amerieiaa Journal of Physiology-Endocrinology and Metabolism,2001,280(5):E816-824.
144 Smith U,Axelsen M,Carvalho E.Elasson B et al.Insulin signaling and action in fat cells:Associations with insulin resistance and type 2diahetes.Annals of the New York Academy of Sciences,1999,92(10):119-126.
145 Kim Y B,Peroni O D,Franke T F et al.Divergent regulalion of Akt1 and Akt2 isoforms in insulin target tissues of obese Zncker rats.Diabetes,2000,49(5):847-856.
146 Tremblav F,Lavigne C,Jacques H et al.Dietry cod protein resores insulin-induceded activaion of phosphatidvlionsitol 3-kinase/Akt and Glut4 translocation to the T-tubules in skeletall muscle of high fat-feel obese rats.Diabetes,2003,52(1):29-37.
147 Kansch C,Krutzfeldt J,Wilke A et al.Effecas of troglilazone on cellular differentiation,insulin signaling and glucose melaholism in cultured human skeletal muscle cells.Biochemical and Biophysical Research communication,2001,280(3):264-267.
148 Ueki K,Yamamoto R,Kahurani Y,et al.Potential role of kinase B in insulin-induced glucose inlucose transport,glycogen synthesis,and protein synthesis.J Biol,Chem,1998,273(9):5315-5322.
149 Cho H,Mu J,Kim Jk,et al.Insulin resistance and a diabetes mellitus-like syndrome in mice lackinn the protein kinase Akt2(PKB beta).Science,2001,292:1728-1731.
150 Schmilz Peiffcr C.Signaling aspecas of insulin resistance in skeletal muscle:mechanisms induced by lipid oversupply.Cellular Signalling,2000,12(9-10):583-594.
151 任婷婷,杨建梅.胰岛素对葡萄糖摄取的调节:细胞内信号通路复杂的相互作用[J].中国糖尿病杂志,2003,11(4):303-304.
152 冯美江,丁新生.Akt与细胞生存[J].国外医学分子生物学分册,2002,24(5):283-285
153 邹伟,李兆育,李春蕾等.蛋白激酶B及其在磷脂酰肌醇3—激酶介导的信号转导中的作用[J].生理科学进展,2000,31(2):120-124.
154 Ilcen L Whileman,Han Cbo,Morris J,Birnbanm.Role of Akt/protein kinasc B in metabolism.Treads is Eadocriadogy and Metabolism,2002,13(12):444-451.
155 马通军,尹潍.TNF-α致胰岛素抵抗的机制[J].国外医学.内分泌学分册,2000,(02).
156 张艳珍,李创鹏,马雅珍,等.针刺治疗急性脑梗死对TNF-a,IL-6及肌力的影响.中国针灸,2001,21(11):677.