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运动改善视黄醇结合蛋白4(RBP4)诱导的胰岛素抵抗的机制研究
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摘要
目的:探讨耐力运动处方以及耐力运动+抗阻运动处方对超重/肥胖青年血清视黄醇结合蛋白4的影响,以及运动处方干预前后视黄醇结合蛋白4与体重、体脂比、BMI、胰岛素抵抗指数、血脂指标、腰围、腰臀比、最大摄氧量等指标之间的关系,明确视黄醇结合蛋白4与胰岛素抵抗之间的关系,以及不同运动处方干预后的变化规律,为运动处方通过影响视黄醇结合蛋白4改善胰岛素抵抗提供理论依据。探讨耐力运动处方对视黄醇结合蛋白4诱导的胰岛素抵抗大鼠骨骼肌、脂肪和肝脏葡萄糖摄取以及胰岛素受体、胰岛素受体底物1蛋白表达和磷酸化的影响;探讨耐力运动处方对视黄醇结合蛋白4诱导的胰岛素抵抗大鼠骨骼肌磷酸肌醇-3-激酶、蛋白酪氨酸磷酸酶表达的影响;探讨耐力运动处方对视黄醇结合蛋白4诱导的胰岛素抵抗大鼠肝脏葡萄糖激酶和磷酸烯醇式丙酮酸羧激酶表达和肝糖原的影响,揭示运动改善视黄醇结合蛋白4诱导的胰岛素抵抗机制。方法:采用BMI为诊断标准,筛选符合标准的超重/肥胖大学生93名;正常体重大学生31名。有氧运动训练组进行12周健身操训练,有氧运动+抗阻肌肉力量训练组进行12周健身操+抗阻肌肉力量训练,运动前后检测实验对象各项指标。重组视黄醇结合蛋白4活体注射的方法获得胰岛素抵抗大鼠模型,随机分为运动组和安静对照组,另设正常安静对照组大鼠。运动组进行3周游泳运动干预,检测大鼠血清视黄醇结合蛋白4、胰岛素抵抗指数等生化指标;免疫组化法分析大鼠骨骼肌、脂肪和肝脏胰岛素受体、胰岛素受体底物1蛋白表达和磷酸化情况,骨骼肌磷酸肌醇-3-激酶、蛋白酪氨酸磷酸酶蛋白表达情况,检测骨骼肌、脂肪和肝脏葡萄糖摄取情况;免疫组化法分析大鼠肝脏葡萄糖激酶和磷酸烯醇式丙酮酸羧激酶表达情况,检测肝糖原含量。结果:(1)运动干预前超重/肥胖者血清视黄醇结合蛋白4水平与体重、BMI、体脂比、胰岛素抵抗指数、腰围、空腹胰岛素、空腹血糖、胆固醇、低密度脂蛋白胆固醇呈正相关,与最大摄氧量、高密度脂蛋白胆固醇呈负相关。(2)12周有氧运动训练显著减少超重/肥胖者血清视黄醇结合蛋白4、体重、BMI、体脂比、空腹胰岛素、胆固醇、甘油三酯、低密度脂蛋白胆固醇、胰岛素抵抗指数、腰围、腰臀比;显著增加最大摄氧量、高密度脂蛋白胆固醇。12周有氧运动+抗阻肌肉力量训练显著减少超重/肥胖者血清视黄醇结合蛋白4、体重、BMI、体脂比、空腹胰岛素、空腹血糖、胆固醇、甘油三酯、低密度脂蛋白胆固醇、胰岛素抵抗指数、腰围、腰臀比;显著增加最大摄氧量、高密度脂蛋白胆固醇。(3)2种运动处方干预后,腰围、腰臀比、空腹血糖、胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇均值差异具有显著性。其它指标均值差异无显著性。(4)有氧运动干预后,超重/肥胖者血清视黄醇结合蛋白4与体重、BMI、腰围、空腹胰岛素、胰岛素抵抗指数呈正相关,与最大摄氧量呈负相关。有氧运动+抗阻肌肉力量训练干预后,超重/肥胖者血清视黄醇结合蛋白4与体重、BMI、腰围、空腹胰岛素、胰岛素抵抗指数呈正相关,与最大摄氧量呈负相关。下降的血清视黄醇结合蛋白4与下降的体重、BMI、体脂比、胰岛素、胰岛素抵抗指数呈正相关。(5)运动组和安静组大鼠血清视黄醇结合蛋白4、胰岛素抵抗指数显著高于正常对照组;运动组大鼠血清视黄醇结合蛋白4、胰岛素抵抗指数显著低于安静组;运动组和安静组大鼠骨骼肌细胞和肝细胞基础状态和胰岛素刺激状态的葡萄糖摄取率均显著低于正常对照组组;与安静组相比,运动组骨骼肌细胞和肝细胞基础状态和胰岛素刺激状态的葡萄糖摄取率显著增加。(6)运动组和安静组大鼠骨骼肌和肝脏胰岛素受体、受体底物1蛋白表达和磷酸化比正常对照组显著减少,运动组大鼠骨骼肌和肝脏胰岛素受体蛋白表达和磷酸化与安静组相比无显著差异。运动组大鼠骨骼肌胰岛素受体底物1磷酸化蛋白表达与安静组相比显著增加。(7)运动组和安静组大鼠骨骼肌磷酸肌醇-3-激酶蛋白表达、葡萄糖摄取率比正常对照组显著减少,运动组大鼠骨骼肌磷酸肌醇-3-激酶蛋白表达、葡萄糖摄取率与安静组相比显著增加。(8)运动组和安静组大鼠骨骼肌蛋白酪氨酸磷酸酶1B蛋白表达比正常对照组显著增加,葡萄糖摄取率显著减少;运动组大鼠骨骼肌蛋白酪氨酸磷酸酶1B蛋白表达与安静组相比显著减少,葡萄糖摄取率显著增加。(9)运动组和安静组大鼠肝脏葡萄糖激酶蛋白表达和活性比正常对照组显著减少,运动组大鼠肝脏葡萄糖激酶蛋白表达和活性与安静组相比显著增加。运动组和安静组大鼠肝脏磷酸烯醇式丙酮酸羧激酶蛋白表达和活性比正常对照组显著增加,运动组大鼠肝脏葡萄糖激酶蛋白表达和活性与安静组相比显著减少。运动组和安静组大鼠肝糖原含量比正常对照组显著减少,运动组大鼠肝糖原含量显著高于安静组。结论:(1)有氧运动和有氧运动+抗阻肌肉力量训练2种运动处方均能够显著降低超重/肥胖青年血清视黄醇结合蛋白4、体重、BMI、体脂比、空腹胰岛素、空腹血糖、胆固醇、甘油三酯、胰岛素抵抗指数、腰围、腰臀比;增加最大摄氧量和高密度脂蛋白胆固醇,改善胰岛素抵抗;2种运动处方干预后,2组超重/肥胖青年间血清视黄醇结合蛋白4水平未出现显著差异。(2)有氧运动和有氧运动+抗阻肌肉力量训练2种运动处方干预后,下降的血清视黄醇结合蛋白4与下降的体重、BMI、体脂比、胰岛素、胰岛素抵抗指数呈正相关。(3)视黄醇结合蛋白4显著抑制大鼠骨骼肌细胞和肝细胞胰岛素受体、胰岛素受体底物1和磷酸肌醇-3-激酶的蛋白表达以及胰岛素受体底物1的磷酸化,降低骨骼肌细胞和肝细胞的葡萄糖摄取率,导致胰岛素抵抗。3周游泳运动干预能够通过解除视黄醇结合蛋白4对大鼠骨骼肌细胞胰岛素受体底物1磷酸化和磷酸肌醇-3-激酶的蛋白表达的抑制,增加骨骼肌细胞葡萄糖摄取率,改善胰岛素抵抗。(4)视黄醇结合蛋白4显著增加大鼠骨骼肌细胞蛋白酪氨酸磷酸酶1B的蛋白表达,降低骨骼肌细胞葡萄糖摄取率,导致胰岛素抵抗。3周游泳运动干预能够降低被视黄醇结合蛋白4增加的大鼠骨骼肌细胞蛋白酪氨酸磷酸酶1B的蛋白表达,增加骨骼肌细胞葡萄糖摄取率,改善胰岛素抵抗。(5)视黄醇结合蛋白4显著抑制大鼠肝脏葡萄糖激酶的表达和活性,增加肝脏磷酸烯醇式丙酮酸羧激酶的表达和活性,减少肝糖合成,增加肝糖异生。3周游泳运动干预能够增加被视黄醇结合蛋白4抑制的大鼠肝脏葡萄糖激酶的表达和活性,降低被视黄醇结合蛋白4增加的大鼠肝脏磷酸烯醇式丙酮酸羧激酶的表达和活性,增加肝糖合成,减少肝糖异生。
Objective To study the effects of aerobic exercise and aerobic exercise+resistance exercise on serum RBP4 in overweight/obesity young man.To discuss the relationship between RBP4 and body mass, body fat percent,blood lipid,body mass index,insulin resistance index,waist circumferenc,waist-hip ratio and V02max before and after exercise prescription.To research the change law and than to provide theory foundation that exercise presciption could improve insulin resistance through the influence in RBP4.To study the effects of aerobic exercise on glucose intake,expression and phosphorylation of insulin receptor and insulin receptor substrate1 in skeletal muscle,adipose tissue and liver of RBP4-induced insulin resistance rats.To study the effects of aerobic exercise on expression of phosphoric acid inositol-3-kinase and protein tyrosine phosphatase 1B in RBP4-induced insulin resistance rats skeletal muscle.To study the effects of aerobic exercise on hepatic glycogen, expression of glucokinase and phosphoenolpyruvate carboxykinase in RBP4-induced insulin resistance rats liver.To proclaim the mechanism that exercise improve RBP4-induced insulin resistance.Method According to BMI,ninety-three overweight/obesity university students were enroled as standard objects.Objects consist of forty-five fale and forty-eight female.Fifteen fale and sixteen female normal weight university students were enroled.Twelve weeks aerobics proceeded in Aerobic exercise group.Twelve weeks aerobics+resisitance exercise proceeded in aerobic exercise+resistance exercise group.Serum RBP4,body mass,body fat percent,body mass index,insulin resistance index,blood lipide,waist circumference,waist-hip ratio and VO2max detected before and after exercise. Recombination RBP4 injected rats to gain insulin resistance rats model. Insulin resistance rats divided into exercise group and quiet group,normal rats enroled as control group.Serum RBP4,insulin resistance index were detected after three weeks swimming.Expression and phosphorylation of insulin receptor and insulin receptor substance1 in skeletal muscle,adipose tissue and liver.Expression of phosphoric acid inositol-3-kinase, protein tyrosine phosphatase 1B and glucose intake were detected in skeletal muscle.Expression of glucokinase, phosphoenolpyruvate carboxykinase and hepatic glycogen were detected in liver.Results (1) There was positive relationshop between serum RBP4 and body mass,body mass index,body fat percent,insulin resistance index,waistcircumference,insulin,blood glucose,cholesterol,low density lipoprotein cholesterol after exercise intervene.There was negative relationship between serum RBP4 and high density lipoprotein cholesterol. (2)Twelve weeks aerobic exercise could notably decrease serum RBP4,body mass,body mass index,body fat percent,insulin, cholesterol,triglyceride,low density lipoprotein cholesterol,insulin resistance index,waist circumference,waist-hip ratio,and could notably increase V02max and high density lipoprotein cholesterol in overweight/obesity yonug university students.Twelve weeks aerobic exercise+resistance exercise could notably decrease serum RBP4,body mass,body massindex,body fat percent,insulin,blood glucose,cholesterol,triglyceride,low density lipoprotein cholesterol, insulin resistance index,waist circumference,waist-hip ratio,and could notably increase V02max and high density lipoprotein cholesterol in overweight/obesity yonug university students. (3) There was not significant difference in RPB4,body mass,body mass index,body fat percent,insulin, insulin resistance index,cholestrol,triglyceride,VO2max between aerobic exercise group and aerobic+resistance exercise group.There was significant difference in waist circumference,waist-hip ratio,blood gucose,high density lipoprotein cholestrol and low density lipoprotein choletrol between aerobic exercise group and aerobic+resistance exercise group. (4) There was positive relationship between RBP4 and body mass,body mass index,waist circumference,insulin, insulin resistance index after aerobic exercise in overweight/obesity. There was negtive relationship between RBP4 and V02max after aerobic exercise in overweight/obesity.There was positive relationship between RBP4 and body mass,body mass index,waist circumference,insulin, insulin resistance index after aerobic+resistance exercise in overweight/obesity. There was negtive relationship between RBP4 and V02max after aerobic+resistance exercise in overweight /obesity.There was positive relationship between decreasing RBP4 and decreasing body mass after aerobic+resistance exercise in overweight/obesity. There was positive relationship betweenΔRBP4 andΔbody mass,ΔBM,Δbody fat percentd,Δinsulin andΔinnsulin resistance index after aerobic+resistance exercise intervene. (5) Serum RBP4 and insulin resistance index increased more in exercise group rats and quiet group rats than control group rats.Serum RBP4 and insulin resistance index decreased more in exercise group rats than quiet group rats.Serum RBP4 and HOMA-IR increasd more in RBP4 intraperitoneal injection exercise groups than nomal control group, respetively.Glucose intake ratio in muscle cells and hepatic cells stimulating with or without insulin decresed more in exercise group rats and quiet group rats than control group.Glucose intake ratio in muscle cells and hepatic cells stimulating with or without insulin increase more in exercise group rats than quiet group rats. (6) Expression and phosphorylation of skeletal cells insulin receptor and insulin receptor substrate 1 decreased more in exercise group rats and quiet group rats than control group rats.There was not difference in expression and phosphorylation of skeletal cells insulin receptor between exercise group rats and quiet group rats.Phosphorylation of skeletal muscle insulin receptor 1 increased more in exercise group rats than quiet rats. (7) Expression of Phosphoric acid inositol-3-kinase and glucose intake ratio decreased more in exercise group rats and quiet group rats' skeletal cells than control group rats.Expression of Phosphoric acid inositol-3-kinase and glucose intake ratio increased more in exercise group rats' skeletal cells than quiet group rats. (8) Expression of protein tyrosine phosphatase IB increased more in exercise group rats and quiet group rats' skeletal cells than control group rats.Glucose intake ratio decreased more in exercise group rats and quiet group rats' skeletal cells than control group rats.Expression of protein tyrosine phosphatase 1B decreased more in exercise group rats' skeletal cells than quiet group rats.Glucose intake ratio increased more in exercise group rats' skeletal cells than quiet group rats. (9) Expression and activity of glucokinase decreased more in exercise group rats and quiet group rats' liver than control group rats.Expression and activity of glucokinase increased more in exercise group rats' liver than quiet group rats.Expression and activity of phosphoenolpyruvate carboxykinase increased more in exercise group rats and quiet group rats' liver than control group rats.Expression and activity of phosphoenolpyruvate carboxykinase decreased more in exercise group rats' liver than quiet group rats.Hepatic glycogen decreased more in exercise group rats and quiet group rats' liver than control group rats.Hepatic glycogen increased more in exercise group rats' liver than quiet group rats.Conclusion (1) Aerobic exercise and aerobic+resistance exercise could notably improve insulin resistance by decreasing serum RBP4,body mass, body mass index,bodyfat percent,insulin,bloodglucose,cholesterol,triglyceride, innsulin resistance index,waist circumference,waist-hip ratio of overweight/obesity youth.Aerobic exercise and aerobic+resistance exercise could notably improve insulin resistance by increasing V02max and high density lipoprotein cholesterol of overweight/obesity youth.There was not difference in serum RBP4 between aerobic exercise group and aerobic+resistance exercise group after exercise intervene. (2) There was positive relationship betweenΔRBP4 andΔbody mass,ΔBM,Δbody fat percentd,Δinsulin andΔinnsulin resistance index after aerobic+resistance exercise intervene. (3) RBP4 could result in insulin resistance by notable suppression the expression and phosphorylation of insulin receptor,insulin receptor substrate 1,Phosphoric acid inositol-3-kinase and glucose intake ratio in skeletal cells and hepatic cells.Three weeks swimming could improve insulin resistance through removing the suppression in insulin receptor substrate 1 phosphorylation and Phosphoric acid inositol-3-kinase expression of skeletal cell by RBP4 and through increasing skeletal cell glucose intake ratio. (4) RBP4 could result in insulin resistance by notable increase the expression of protein tyrosine phosphatase 1B and decrease glucose intake ratio in skeletal cell.Three weeks swimming could improve insulin resistance through removing the increase in protein tyrosine phosphatase 1B expression of skeletal cell by RBP4 and through increasing skeletal cell glucose intake. (5) RBP4 could notably restrain expression and activity of glucokinase in liver,increase expression and activity of phosphoenolpyruvate carboxykinase,decrease glycogen synthetize and increase glycogen heteroplasia.Three weeks swimming could increase expression and activity suppressed of glucokinase by RBP4,decrease expression and activity of phosphoenolpyruvate carboxykinase increased by RBP4,increase glycogen synthetize and decrease glycogen heteroplasia.
引文
[1]Frolik CA. Metabolism of retinoids. Orlando. Orlando:Academic ress, 1984:177.
    [2]Dawson MI. Chemistry and biology of syntheic retinoids. Boca Raton. Boca Raton:CRC Press,1990.
    [3]William J. Lennarz MDL. Encyclopedia of Biological Chemistry. Elsevier Pte Itd:Elsevier Pte Itd,2006:355.
    [4]Monaco HL, Rizzi M, Coda A. Structure of a complex of two plasma proteins: transthyretin and retinol-binding protein. Science,1995, 268(5213):1039-1041.
    [5]Naylor HM, Newcomer ME. The structure of human retinol-binding protein (RBP) with its carrier protein transthyretin reveals an interaction with the carboxy terminus of RBP.Biochemistry,1999, 38(9):2647-2653.
    [6]Cendron L, Trovato A, Seno F, etal. Amyloidogenic potential of transthyretin variants:insights from structural and computational analyses. J Biol Chem,2009,284(38):25832-25841.
    [7]Hornberg A, Eneqvist T, Olofsson A, et al.A comparative analysis of 23 structures of the amyloidogenic protein transthyretin. J Mol Biol,2000, 302(3):649-669.
    [8]Yang Q, Graham TE, Mody N, et al. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature,2005,436 (21):356-362.
    [9]Barbara B, Kahn, Jeffrey S.Obesity and insulin resistance.J Clin Invest,2000,106(4):473-481.
    [10]Paul T, John HB. Physiological role of adipose tissue:white adipose tissue as an endocrine and secretory organ. Proceedings of the Nutrition Society,2001,60:329-339.
    [11]Graham TE, Yang Q, Bluher M. Retinol-Binding Protein 4 and Insulin Resistance in Lean, Obese, and Diabetic Subjects. N Engl J Med,2006, 354:2552-2563.
    [12]潘优津,吴朝明.胰岛素抵抗综合征患者血视黄醇结合蛋白4和脂联素的相关 性研究.中国病理生理杂志,2008,24(3):597-598、601.
    [13]周文平.肥胖患者血清视黄醇结合蛋白4水平变化及与性激素的相关性.中国医科大学学报,2008,37(2):230-233.
    [14]Mohlig M, Weickert MO, Ghadamgahi E, et al. Retinol-binding protein 4 is associated with insulin resistance, but appears unsuited for metabolic screening in women with polycystic ovary syndrome. Eur J Endocr. 2008,158:517-523.
    [15]Ling L, BAO Y, et al. Serum retinol binding protein 4 is associated with insulin secretion in Chinese with normal glucose tolerance. Diabet,2009,24(1):1-13.
    [16]Kowalska I, Straczkowski M,Adamska A, et al. Serum Retinol Binding Protein 4 Is Related to Insulin Resistance and Nonoxidative Glucose Metabolism in Lean and Obese Women with Normal Glucose Tolerance. J Clin Endoc Metab,2008,16:2786-2789.
    [17]Reinehr T, Stoffel-Wagner B, Roth CL. Retinol-binding protein 4 and its relation to insulin resistance in obese children before and after weight loss. J Clin Endoc Metab,2008,93(6):2287-2293.
    [18]Aeberli I, Biebinger R, Lehmann R, et al. Serum retinol-binding protein 4 concentration and its ratio to serum retinol are associated with obesity and metabolic syndrome components in children. J Clin Endoc Metab,2007,92:4359-4365.
    [19]Q Qi, Z Yu, X Ye, et al. Elevated retinol-binding protein 4 levels are associated with metabolic syndrome in Chinese people. J Clin Endoc Metab.2007,92:4827-4834.
    [20]Hammarstedt A, Pihlajamaki J, Graham TE. High circulating levels of RBP4 and mRNA levels of aP2, PGC-la and UCP-2 predict improvement in insulin sensitivity following pioglitazone treatment of drug-naive type 2 diabetic subjects. J Inter Med,2008,263:440-449.
    [21]Jia W, Wu H, Bao Y et al. Association of serum retinol-binding protein 4 and visceral adiposity in Chinese subjects with and without type 2 diabetes. J Clin Endoc Metab,2007,92:3224-3229.
    [22]梁学颖,徐琪寿.视黄醇结合蛋白的分子生物学.生理科学进展,2000,(03):277-279.
    [23]Munkhtulga L, Nakayama K, Utsumi N, et al. Identification of a regulatory SNP in the retinol binding protein 4 gene associated with type 2 diabetes in Mongolia. Hum Genet,2007,120(6):879-88.
    [24]Craig RL, Chu WS, Elbein SC. Retinol binding protein 4 as a candidate gene for type 2 diabetes and prediabetic intermediate traits. Mol Genet Metab,2007,90(3):338-44.
    [25]Hu C, Jia W, Zhang R, et al. Effect of RBP4 gene variants on circulating RBP4 concentration and type 2 diabetes in a Chinese population. Diabet Med,2008,25(1):11-18.
    [26]Munkhtulga L, Nagashima S, Nakayama K, et al. Regulatory SNP in the RBP4 gene modified the expression in adipocytes and associated with BMI. Obesity (Silver Spring),20-10,18(5):1006-1014.
    [27]Choi KM, Kim TN, Yoo HJ,et al. Effect of exercise training on A-FABP, lipocalin-2 and RBP4 levels in obese women. Clin Endocri,2009,70: 569-574.
    [28]Wolf G. Serum Retinol-Binding Protein:A Link Between Obesity, Insulin Resistance,and Type 2 Diabetes.Nutri Revi,2007,65(5) :251-256.
    [29]Choi SH, Lee YJ, Park YJ, et al. Retinol binding protein-4 elevation is associated with serum thyroid-stimulating hormone level independently of obesity in elderly subjects with normal glucose tolerance. J Clin Endocri Metab,2008,93(6):2313-2318.
    [30]Vitkova M, Kovacikova E, Kovacikova M, et al. Plasma levels and adipose tissue messenger ribonucleic acid expression of retinol-binding protein 4 are reduced during calorie restriction in obese subjects but are not related to diet-induced changes in insulin sensitivity. Clin Endocr Metab,2007,92(6):2330-2335.
    [31]Yao-Borengasser, Varma A,Bodles AM, et al. Retinol Binding Protein 4 Expression in Humans:Relationship to Insulin Resistance, Inflammation, and Response to Pioglitazone. J Clin Endocr Metab,2007, 92(7):2590-2597.
    [32]Janke J, Engeli S, Boschmann M, et al. Retinol-binding protein 4 in human obesity. Diabet,2006,55:2805-2810.
    [33]Chavez AO, Coletta DK, Kamath S, et al.Retinol-binding protein 4 is associated with impaired glucose tolerance but not with whole body or hepatic insulin resistance in Mexican Americans.Am J Physiol Endocr Metab,2009,296(4):E758-764.
    [34]Krzyzanowska K,Zemany L,Krugluger W, et al. Serum concentrations of retinol-binding protein 4 in women with and without gestational diabetes. Diabet,2008,51 (7):1115-1122.
    [35]Eynatten MV, Lepper PM, Liu D, et al. Retinol-binding protein 4 is associated with components of the metabolic syndrome, but not with insulin resistance, in men with type 2 diabetes or coronary artery disease. Diabet,2007,50(9):1930-1937.
    [36]Gomez-Ambrosi J, Rodriguez A, Catalan V, et al. Serum retinol-binding protein 4 is not increased in obesity or obesity-associated type 2 diabetes mellitus, but is reduced after relevant reductions in body fat following gastric bypass. Clin Endocr (Oxf).2008,69 (2):208-215.
    [37]Reinehr T, Stoffel-Wagner B, Roth CL. Retinol-Binding Protein 4 and Its Relation to Insulin Resistance in Obese Children before and after Weight Loss. J Clin Endocr Metab,2008,93(6):2287-2293.
    [38]Lim S, Choi SH, Jeong IK, et al. Insulin-sensitizing effects of exercise on adiponectin and retinol-binding protein-4 concentrations in young and middle-aged women. J Clin Endoc Metabo,2008,93:2263-2268.
    [39]张明军.游泳运动后2型糖尿病鼠脂肪RBP4mRNA表达与胰岛素敏感性的相关性研究.福建体育科技,2008,27(5):44-46.
    [40]王清生,张明军.游泳运动对2型糖尿病大鼠脂肪组织、肝脏RBP4mRNA表达的影响.北京体育大学学报,2009,32(3):61-63.
    [41]王清生,张明军.8周游泳运动对糖尿病大鼠RBP4mRNA表达的影响.山东体育学院学报,2008,24(8):44-46.
    [42]张明军,王清生.游泳运动和葛根素干预对2型糖尿病大鼠脂肪组织RBP4表达的影响.河南中医学院学报,2008,23(139):17-19.
    [43]Episkopou V, Maeda S, Nishiguchi S, etal. Disruption of the transthyretin gene results in mice with depressed levels of plasma retinol and thyroid hormone.Proc Natl Acad Sci USA,1993,90(6): 2375-2379.
    [44]Berni R, Formelli F.In vitro interaction of fenretinide with plasma retinol-binding protein and its functional consequences. FEBS.1992, 308(1):43-45.
    [45]Formelli F, Carsana R, Costa A, et al. Plasma retinol level reduction by the synthetic retinoid fenretinide:a one year follow-up study of breast cancer patients. Cancer Res,1989,49(21):6149-6152.
    [46]Kloting N, Graham TE, Berndt J, et al. Serum retinol-binding protein is more highly expressed in visceral than in subcutaneous adipose tissue and is a marker of intra-abdominal fat mass. Cell Metab,2007,6(1): 79-87.
    [47]Mody N, Graham TE,Tsuji Y, et al. Decreased clearance of serum retinol-binding protein and elevated levels of transthyretin in insulin-resistant ob/ob mice. Am J Physiol Endocr Metab,2008,294(4): E785-793.
    [48]Balagopal P, Graham TE,Kahn BB, et al. Reduction of elevated serum retinol binding protein in obese children by lifestyle intervention: association with subclinical inflammation.J Clin Endocr Metab,2007, 92(5):1971-1974.
    [49]克劳斯G.信号转导语调控的生物化学.北京:化学工业出版社,2005:242-243.
    [50]Danielsson A, Ost A, Lystedt E. Insulin resistance in human adipocytes occurs downstream of IRS1 after surgical cell isolation but at the level of phosphorylation of IRS1 in type 2 diabetes. FEBS,2005,272(1):141-151.
    [51]Danielsson A, Ost A,Nystrom FH,et al. Attenuation of insulin-Stimulated insulin receptor substrate-1 serine 307 phosphorylation in insulin resistance of type 2 diabetes. J Biol Chemi,2005,280: 34389-34392.
    [52]Danielsson A, Nystrom FH, Stralfors P. Phosphorylation of IRS1 at serine 307 and serine 312 in response to insulin in human adipocytes. Biochem Biophys Res Commun,2006,342(4):1183-1187.
    [53]Ost A, Danielsson A, Liden M, et al. Retinol-binding protein-4 attenuates insulin-induced phosphorylation of IRS1 and ERK1/2 in primary human adipocytes. FASEB,2007,21(13):3696-3704.
    [54j DeFronzo RA. Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med,1999,131(4):281-303.
    [55]Matschinsky FM. A lesson in metabolic regulation inspired by the glucokinase glucose sensor paradigm. Diabet,1996,45 (2):223-241.
    [56]Brown KS, Kalinowski SS, Megill JR, et al. Glucokinase regulatory protein may interact with glucokinase in the hepatocyte nucleus. Diabet,1997, 46(2):179-86.
    [57]Grupe A, Hultgren B, Ryan A, et al. Transgenic knockouts reveal a critical requirement for pancreatic beta cell glucokinase in maintaining glucose homeostasis. Cell,1995,83(1):69-78.
    [58]Postic C, Shiota M,Niswender KD, et al. Dual roles for glucokinase in glucose homeostasis as determined by liver and pancreatic β cell-specific gene knock-outs using Cre recombinase. J Biol,1999, 274(1):305-315.
    [59]Ferre T, Riu E,Bosch F, etal.Evidence from transgenic mice that glucokinase is rate limiting for glucose utilization in the liver. FASEB,1996,10(10):1213-1218.
    [60]Desai UJ, Slosberg ED, Boettcher BR, et al. Phenotypic correction of diabetic mice by adenovirus-mediated glucokinase expression. Diabetes. 2001.50(10):2287-95.
    [61]Froguel P,Zouali H, Vionnet N, et al.Familial hyperglycemia due to mutations in glucokinase. Definition of a subtype of diabetes mellitus. N Engl J Med,1993,328(10):697-702.
    [62]Njolstad PR, Sagen JV, Bjorkhaug L, et al. Permanent neonatal diabetes caused by glucokinase deficiency:inborn error of the glucose-insulin signaling pathway. Diabet,2003,52(11):2854-2860.
    [63]Gloyn AL, Noordam K, Willemsen MA, et al. Insights into the biochemical and genetic basis of glucokinase activation from naturally occurring hypoglycemia mutations. Diabet,2003,52(9): 2433-2440.
    [64]Lepiniec L, Vidal J,Chollet R, etal. Phosphoenolpyruvate arboxylase structure, regulation and evolution. Plant Sci,1994,99(2):111-124.
    [65]Dong LY, Masuda T, Kawamura T, et al. Cloning, expression, and characterization of a root-form phosphoenolpyruvate carboxylase from Zea mays:comparison with the C4-form enzyme. Plant Cell Physiol,1998, 39(8):865-873.
    [66]Nakamura I,Takahashi N,Sasaki T, et al. Wortmannin, a specific inhibitor of phosphatidylinositol-3 kinase, blocks osteoclastic bone resorption. FEBS,1995,361 (1):79-84.
    [67]Chandramouli V,Ekberg K,SchumannWC, et al. Quantifying gluconeo genesis during fasting. Am J Physiol,1997,273(6Pt1):E1209-1215.
    [68]Petersen KF, Price TB, Bergeron R. Regulation of net hepatic glycogenolysis and gluconeogenesis during exercise:impact of type 1 diabetes. J Clin Endocr Metab,2004,89(9):4656-4664.
    [69]Boden G, Chen X,Stein TP.Gluconeogenesis in moderately and severely hyperglycemic patients with type 2 diabetes mellitus. Am J Physiol Endocr Metab,2001,280(1):E23-30.
    [70]Wajngot A,Chandramouli V,Schumann WC, et al.Quantitative contributions of gluconeogenesis to glucose production during fasting in type 2 diabetes mellitus. Metabo,2001,50(1):47-52.
    [71]Hanson RW, Garber AJ. Phosphoenolpyruvate carboxykinaseI. Its role in gluconeogenesis. Am J Clin Nutr,1972,25(10):1010-1021.
    [72]Rognstad R. Rate-limiting steps in metabolic pathways. J Biol Chem,1979, 254(6):1875-1878.
    [73]Veneziale CM, Donofrio JC,Nishimura H. The concentration of P-enolpyruvate carboxykinase protein in murine tissues in diabetes of chemical and genetic origin. J Biol Chem,1983,258(23):14257-14262.
    [74]Valera A,Pujol A, Pelegrin M, et al. Transgenic mice overexpressing phosphoenolpyruvate carboxykinase develop non-insulin-dependent diabetes mellitus. Proc Natl Acad Sci USA,1994,91 (19):9151-9154.
    [75]Friedman JE, Yun JS, Patel YM, et al. Glucocorticoids regulate the induction of phosphoenolpyruvate carboxykinase (GTP) gene trans cription during diabetes. J Biol Chem,1993,268(17):12952-12957.
    [76]Ferber S, Meyerovitch J,Kriauciunas KM, etal. Vanadate normalizes hyperglycemia and phosphoenolpyruvate carboxykinase mRNA levels in ob/ob mice. Metabo,1994,43(11):1346-1354.
    [77]Franckhauser S,Munoz S,Pujol A, et al. Increased fatty acid re-esterification by PEPCK overexpression in adipose tissue leads to obesity without insulin resistance. Diabet,2002,51 (3):624-630.
    [78]Chakravarty K, Cassuto H,Reshef L, et al. Factors that control the tissue-specific transcription of the gene for phosphoenolpyruvate carboxykinase-C. Crit Rev Biochem Mol Biol,2005,40(3):129-154.
    [79]Shin DJ,Odom DP, Scribner KB, et al. Retinoid regulation of the phosphoenolpyruvate carboxykinase gene in liver. Mol Cell Endocr,2002, 195(1-2):39-54.
    [80]中华人民共和国卫生部疾病控制司.中国成人超重和肥胖症预防与控制指南.北京:卫生部疾病控制司,2003.
    [81]Kershaw EE. Adipose tissue as an endocrine organ.J Clin Endocr Metabo,2004,89(6):2548-2556.
    [82]Young JB, Landsberg L.Stimulation of the sympathetic nervous system during sucrose feeding. Nature,1997,269:615-617.
    [83]Mohlig M, Weickert MO, Ghadamgahi E, et al. Retinol-binding protein 4 is associated with insulin resistance, but appears unsuited for metabolic screening in women with polycystic ovary syndrome. Eur J Endocr,2008, 158(4):517-23.
    [84]Yao-Borengasser A,Varma V,Bodles AM. Retinol Binding Protein 4 Expression in Humans:Relationship to Insulin Resistance, Inflammation, and Response to Pioglitazone. J Clin Endocr Metabo,2006, 92(7):2590-2597.
    [85]Mercader J, Granados N, Caimari A, et al. Retinol-binding protein 4 and nicotinamide phosphoribosyltransferase/visfatin in rat obesity models. Horm Metab Res,2008,40(7):467-72.
    [86]Dominik G, Haider KS,Prager G. Serum Retinol-Binding Protein 4 Is Reduced after Weight Loss in Morbidly Obese Subjects.J Clin Endocr Metabo,2006,92(3):1168-1171.
    [87]Balagopal P, Graham TE, Kahn BB. Reduction of Elevated Serum Retinol Binding Protein in Obese Children by Lifestyle Intervention Association with Subclinical Inflammation. J Clin Endocr Metabo,2006, 92(5):1971-1974.
    [88]Vitkova M, Klimcakova E, Kovacikova M. Plasma Levels and Adipose Tissue Messenger Ribonucleic Acid Expression of Retinol-Binding Protein 4 Are Reduced during Calorie Restriction in Obese Subjects but Are Not Related to Diet-Induced Changes in Insulin Sensitivity. J Clin Endocr Metabo,2006,92 (6):2330-2335.
    [89]Lim S, Choi SH, Jeong IK, et al. Insulin-sensitizing effects of exercise on adiponectin and retinol-binding protein-4 concentrations in young and middle-aged women. J Clin Endocr Metab,2008,93(6):2263-2268.
    [90]Choi KM, Kim TN, Yoo HJ,et al. Effect of exercise training on A-FABP, lipocalin-2 and RBP4 levels in obese women. Clin Endocr (Oxf),2009, 70(4):569-574.
    [91]田野.高级运动生理学教程.北京:高等教育出版社,2003.
    [92]Halaas JL, Gajiwala KS, Maffei M, et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science,1995,269(5223): 543-546.
    [93]Kershaw EE. Adipose Tissue as an Endocrine Organ. J Clin Endocr Metab,2004,89(6):2548-2556.
    [94]Steppan CM, Lazar MA. Resistin and obesity-associated insulin resistance.Trends Endocr Metabo,2002,13(11):18-23.
    [95]Mody N, Graham TE, Tsuji Y, et al. Decreased clearance of serum retinol-binding protein and elevated levels of transthyretin in insulin-resistant ob/ob mice. Am J Physiol Endocr Metab,2008,294(4): E785-793.
    [96]Monaco HL, Rizzi M, Coda A. Structure of a complex of two plasma proteins: transthyretin and retinol-binding protein. Scienc,1995,268(5213): 1039-1041.
    [97]Makover A, Soprano DR, Wyatt ML. Localization of ret inol-binding protein messenger RNA in the rat kidney and in perinephric fat tissue. J Lipid Res,1989,30:171-180.
    [98]Tsutsumi C, Okuno M, Tannous L.Retinoids and Retinoid-bindingP rotein Expression in Rat Adipocytes. J Biol Chem,1992,267(3):1805-1810.
    [99]Cho YM, Youn BS, Lee H, et al. Plasma Retinol-Binding Protein-4 Concentrations Are Elevated in Human Subjects With Impaired Glucose Tolerance and Type 2 Diabetes. Am Diabet Assoc,2006,29(11):2457-2461.
    [101]Janke J, Engeli S, Boschmann M. Retinol-Binding Protein 4 in Human Obesity. Diabet,2006,55:2805-2810.
    [102]Goodman DWS. Plasma retinol-binding protein. New York:Raven,1994: 257-282.
    [103]Tamori Y, Sakaue H, Kasuga M. RBP4, an unexpected adipokine. Nature Med, 2006,12(1):30-31.
    [104]Kowalska I, Straczkowski M, Adamska A, et al. Serum retinol binding protein 4 is related to insulin resistance and nonoxidative glucose metabolism in lean and obese women with normal glucose tolerance. J Clin Endocr Metab,2008,93(7):2786-2789.
    [105]Lee JW, Lee HR, Shim JY, et al. Abdominal visceral fat reduction is associated with.favorable changes of serum retinol binding protein-4 in nondiabetic subjects.Endocr J,2008,55(5):811-818.
    [106]Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabet,1985,25:1154-1161.
    [107]Mallat Z, Simon T, Benessiano J, et al. Retinol-binding protein 4 and prediction of incident coronary events in healthy men and women. J Clin Endocr Metab,2009,94(1):255-260.
    [108]Usui S,Ichimura M,Ikeda S, et al. Association between serum retinol-binding protein 4 and small dense low-density lipoprotein cholesterol levels in young adult women. Clin Chim Acta,2009, 399(1-2):45-48.
    [109]Cheng X, Zhang H. Serum retinal-binding protein 4 is positively related to insulin resistance in Chinese subjects with type 2 diabetes. Diabetes Res Clin Pract,2009,84(1):58-60.
    [110]Mallat Z, Simon T, Benessiano J, et al. Retinol-binding protein 4 and prediction of incident coronary events in healthy men and women. J Clin
    Endocr Metab,2009,94(1):255-260.[111]许曼音.糖尿病学.上海:上海科学技术出版社,2010.[112] Quadro L, Blaner WS, Salchow DJ. Impaired retinal function and vitaminA availability in mice lacking retinol.EMBO,1999,17(18): 4633-4644. [113] Ploug T, Stallknecht BM. Effect of endurance training on glucose transport capacity and glucose transporter expression in rat skeletal muscle. Am J Physiol,1990,259E:778-784. [114] Fang X,Palanivel R, Zhou X,et al. Hyperglycemia-and hyperinsulinemia-induced alteration of adiponectin receptor expression and adiponectin effects in L6 myoblasts. J Mol Endocr,2005,35:465-476. [115] White MF. The insulin signalling system and the IRS proteins. Diabetologia,1997,40:S2-S17.[116]黄文林,朱孝峰.信号转导.北京:人民卫生出版社,2002:157.[117] Hubbard SR,Till JH. Protein tyrosine kinase structure and function. Annu Rev Biochem,2000,69:373-398. [118] Pawson T. Regulation and targets of receptor tyrosine kinases. Eur J Cancer,2002,38Suppl 5:S3-10. [119] Lemmon MA, Schlessinger J.Cell signaling by receptor tyrosine kinases. Cell,2010,141 (7):1117-1134. [120] Feener EP,Backer JM, King GL, et al. Insulin stimulates serine and tyrosine phosphorylation in the juxtamembrane region of the insulin receptor. J Biol Chem,1993,268 (15):11256-11264. [121] White MF, Kahn CR. The insulin signaling system. J Biol Chem,1994, 269(1):1-4. [122] McClain DA, Maegawa H,Levy J, et al. Properties of a human insulin receptor with a COOH-terminal truncation. I. Insulin binding, autophosphorylation, and endocytosis. J Biol Chem,1988,263 (18): 8904-11. [123] White MF, Shoelson SE, Keutmann H, et al.A cascade of tyrosine autophosphorylation in the beta-subunit activates the phosphotransferase of the insulin receptor. J Biol Chem,1988,263(6): 2969-2980.
    [124]Vogt B, Carrascosa JM,Ermel B, et al.The two isotypes of the human insulin receptor (HIR-A and HIR-B)follow different internalization kinetics. Biochem Biophys Res Commun,1991,177(3):1013-1018.
    [125]Wilden PA, Siddle K, Haring E, et al. The role of insulin receptor kinase domain autophosphorylation in receptor-mediated activities. Analysis with insulin and anti-receptor antibodies. J Biol Chem,1992,267(19):13719-13727.
    [126]Songyang Z, Carraway KL, Eck MJ, et al. Catalytic specificity of protein-tyrosine kinases is critical for selective signalling. Nature, 1995,373(6514):536-539.
    [127]White MF, Yenush L.The IRS-signaling system:a network of docking proteins that mediate insulin and cytokine action. Curr Top Microbiol Immunol,1998,228:179-208.
    [128]Sun XJ, Crimmins DL, Myers Jr, et al. Pleiotropic insulin signals are engaged by multisite phosphorylation of IRS-1. Mol Cell Biol.1993, 13(12):7418-7428.
    [129]Rocchi S, Tartare-Deckert S, Mothe I, et al. Identification by mutation of the tyrosine residues in the insulin receptor substrate-1 affecting association with the tyrosine phosphatase 2C and phosphatidylinositol 3-kinase. Endocr,1995,136(12):5291-5297.
    [130]White MF. IRS proteins and the common path to diabetes. Am J Physiol Endocr Metab,2002,283(3):E413-422.
    [131]Luo M, Reyna S,Wang L, et al. Identification of insulin receptor substrate 1 serine/threonine phosphorylation sites using mass spectrometry analysis:regulatory role of serine 1223. Endocr,2005, 146(10):4410-4416.
    [132]Aguirre V,Werner ED,Giraud J, et al. Phosphorylation of Ser307 in insulin receptor substrate-1 blocks interactions with the insulin receptor and inhibits insulin action. J Biol Chem,2002,277 (2): 1531-1537.
    [133]Mothe I,Van Obberghen E.Phosphorylation of insulin receptor substrate-1 on multiple serine residues,612,632,662, and 731, modulates insulin action. J Biol Chem,1996,271(19):11222-11227.
    [134]CoraWeigert AH, Tasja Brischmann. The Phosphorylation of Ser318 of Insulin Receptor Substrate 1 Is Not per se Inhibitory in SkeletalMuscle Cells but Is Necessary to Trigger the ttenuation of the Insulin-stimulated Signal. J biol chem.,2002,280(45):37393-37399.
    [135]唐东华,姚起新,亓竹青等.17β-雌二醇上调去卵巢胰岛素抵抗大鼠骨骼肌中胰岛素受体的表达.中华内分泌代谢杂志,2010,26(8):695-698.
    [136]陈三妹,王蓉蓉,牛三强等.糖尿病非酒精性脂肪肝病大鼠肝组织胰岛素受体、瘦素受体mRNA的表达.中国病理生理杂志,2009,25(7):1370-1375.
    [137]葛伊莉.糖尿病和硝化条件下胰岛素受体及底物酪氨酸磷酸化的研究.无机化学学报,2008,24(7):140-1045.
    [138]王光浩.黄蔑多糖对糖尿病大鼠肾组织胰岛素受体及其底物1的影响.时珍国医国药,2007,18:2344-2345.
    [139]裴海成.男性肥胖患者胰岛素受体的改变及意义.第二军医大学学报,2003,24:340.
    [140]王慧敏.胰岛素抵抗大鼠肝脏丝氨酸-酪氨酸磷酸化IRS1表达异常与脂联素相关的研究.中国医科大学学报,2009,38(4):250-252.
    [141]李喜莲,王针织,俞超芹.补肾活血化瘀方上调雄激素致不孕大鼠脂肪组织中胰岛素受体底物1及其酪氨酸磷酰化.中西医结合学报,2006,6(6):621-625.
    [142]吕立群.多囊卵巢综合征合并胰岛素抵抗患者子宫内膜胰岛素受体底物1-2蛋白的表达及酪氨酸磷.华中科技大学学报(医学版),2008,37(4):473-475.
    [143]燕晓雯.骨骼肌胰岛素受体底物1及其丝氨酸磷酸化与酪氨酸磷酸化在感染大鼠胰岛素抵抗中的作.中华医学杂志,2006,86(41):2923-2927.
    [144]刘义,邓小艳.罗格列酮对多囊卵巢综合征患者卵巢黄素化颗粒细胞胰岛素受体底物1和2蛋白表达及酪氨酸磷酸化的影响.中国病理生理杂志,2008,24(8):1620-1624.
    [145]朱颖.妊娠期糖尿病患者腹部皮下脂肪组织胰岛素受体底物表达及其酪氨酸磷酸化的变化.实用医学杂志,2009,25(23):3962-3965.
    [146]李红发.胰岛素受体底物1蛋白表达及其酪氨酸磷酸化程度与多囊卵巢综合征发病的关系.中华妇产科杂志,2004,39(3):176-179.
    [147]Danielsson A, Ost A, Nystrom FH, et al. Attenuation of insul in-stimulated insulin receptor substrate-1 serine 307 phosphorylation in insulin resistance of type 2 diabetes. J Biol Chem,2005,280(41):34389-34392.
    [148]Goropashnaya AV, Herron J, Sexton M, et al. Relationships between plasma adiponectin and body fat distribution, insulin sensitivity, and plasma lipoproteins in Alaskan Yup'ik Eskimos:the Center for Alaska Native Health Research study. Metab,2009,58(1):22-29.
    [149]Mao X, Kikani CK, Riojas RA,et al. APPL1 binds to adiponectin receptors and mediates adiponectin signalling and function. Nat Cell Biol,2006,8(5):516-523.
    [150]Combs TP, Pajvani UB, Berg AH, et al. A transgenic mouse with a deletion in the collagenous domain of adiponectin displays elevated circulating adiponectin and improved insulin sensitivity. Endocr,2004,145(1):367-383.
    [151]Gu Y,Wang G,Pan G, et al. Transport and bioavailability studies of astragaloside IV, an active ingredient in Radix Astragali. Basic Clin Pharmacol Toxicol,2004,95(6):295-298.
    [152]Habecker BA, Martin JM, Nathanson NM. Isolation and characterization of a novel cDNA which identifies both neural-specific and ubiquitously expressed GS alpha mRNAs. J Neurochem,1993,61 (2):712-717.
    [153]Lee YH, Giraud J, Davis RJ, et al. c-Jun N-terminal kinase (JNK) mediates feedback inhibition of the insulin signaling cascade. J Biol Chem,2003,278(5):2896-2902.
    [154]Yu-Hung Chang KL, Wang C.Elevated serum retinol-binding protein 4 concentrations are associated with renal dysfunction and uric acid in type 2 diabetic patients. Diabetes Metab Res Rev,2008, (24):629-634.
    [155]Seiji Inoue NT, Akahori Y. Elevated level of serum retinol-binding protein 4 in pregnancy-induced hypertension. Japan Soci Obst Gynec,2009,35(2):293-300.
    [156]Cabre A, Lazaro I, Girona J, et al. Retinol-binding protein 4 as a plasma biomarker of renal dysfunction and cardiovascular disease in type 2 diabetes. J Inter Med,2007,262:496-503.
    [157]Gomez-AmbrosiJ, Rodriguez A,Catalan V, et al. Serum retinol-binding protein 4 is not increased in obesity or besity-associated type 2 diabetes mellitus, but is reduced after relevant reductions in body fat following gastric bypass. Clin Endocr,2008,69:208-205.
    [158]Heled Y, Shapiro Y,Shani Y,et al. Physical exercise enhances protein kinase C delta activity and insulin receptor tyrosine phosphorylation in diabetes-prone psammomys obesus. Metab,2003,52(8):1028-1033.
    [159]钱荣,谈艳,汪宗宝等.不同运动强度下糖尿病大鼠骨骼肌胰岛素受体mRNA表达及氧化应激变化.第三军医大学学报,2010,32(9):926-929.
    [160]胡永善.运动对糖尿病大鼠肝细胞膜胰岛素受体的影响.中国康复医学杂志,1997,(3):4-7.
    [161]范振华.运动对糖尿病大鼠骨骼肌细胞胰岛素受体的影响.中国运动医学杂志,1998,(3):14-17.
    [162]Wadley GD, Tunstall RJ, Sanigorski A, et al. Differential effects of exercise on insulin-signaling gene expression in human skeletal muscle. J Appl Physiol,2001,90(2):436-440.
    [163]Chibalin A. Exercise-induced changes in expression and activity of proteins involved in insulin signal transduction in skeletal muscle: differential effects on insulin-receptor substrates 1 and 2. Proc Natl Acad Sci USA,2000,97(1):38-43.
    [164]Cusi K, Maezono K, Osman A, et al. Insulin resistance differentially affects the PI 3-kinase- and MAP kinase-mediated signaling in human muscle.J Clin Invest,2000,105(3):311-320.
    [165]Luciano E,Carneiro EM,Carvalho CR, et al. Endurance training improves responsiveness to insulin and modulates insulin signal transduction through the phosphatidylinositol 3-kinase/Akt-1 pathway. Eur J Endoc,2002,147(1):149-157.
    [166]Saengsirisuwan V, Perez FR, Sloniger JA, et al. Interactions of exercise training and alpha-lipoic acid on insulin signaling in skeletal muscle of obese Zucker rats. Am J Physiol Endocr Metab,2004,287 (3):E529-536.
    [167]Peres SB, Moraes SM, Costa CE, et al. Endurance exercise training increases insulin responsiveness in isolated adipocytes through IRS/PI3-kinase/Akt pathway. J Appl Physiol,2005,98(3):1037-1043.
    [168]Ropelle ER, Pauli JR, Prada PO, et al. Reversal of diet-induced insulin resistance with a single bout of exercise in the rat:the role of PTP1B and IRS-1 serine phosphorylation. J Physiol,2006,577(3):97-1007.
    [169]Silva DA, Adelion SR, Joser P, et al.Exercise Intensity, Inflammatory Signaling and Insulin Resistance in Obese Rats. Med Sci Spor Exerc,2010, (42)12:2180-2188.
    [170]Wadley GD, Konstantopoulos N, Macaulay L,et al. Increased insulin-stimulated Akt pSer473 and cytosolic SHP2 protein abundance in human skeletal muscle following acute exercise and short-term training. J Appl Physiol,2007,102(4):1624-1631.
    [171]Wilson C, Hargreaves M, Howlett KF. Exercise does not alter subcellular localization, but increases phosphorylation of insulin-signaling proteins in human skeletal muscle. Am J Physiol Endocr Metab,2006,290(2):E341-346.
    [172]Fatone C, Guescini M, Balducci S, et al. Two weekly sessions of combined aerobic and resistance exercise are sufficient to provide beneficial effects in subjects with Type 2 diabetes mellitus and metabolic syndrome.J Endocr Invest,2010,33(7):489-495.
    [173]Krisan AD, Collins DE, Crain AM, et al. Resistance training enhances components of the insulin signaling cascade in normal and high-fat-fed rodent skeletal muscle. J Appl Physiol,2004,96(5):1691-1700.
    [174]Baron AD, Brechtel G,Wallace P. Rates and tissue sites of non-insulin-and insulin-mediated glucose uptake in humans. Am J Physiol Endocr Metab,1988,255:E769-E774.
    [175]Kruszynska YT, Worrall DS,Ofrecio J, et al.Fatty acid-induced insulin resistance:decreased muscle PI3K activation but unchanged Akt phosphorylation. J Clin Endocr Metab,2002,87(1):226-234.
    [176]Dresner A, Laurent D,Marcucci M, et al. Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity. J Clin Invest,1999,103(2):253-259.
    [177]Fasshauer M, Klein J, Ueki K, et al. Essential role of insulin receptor substrate-2 in insulin stimulation of Glut4 translocation and glucose uptake in brown adipocytes.J Biol Chem,2000,275(33):25494-25501.
    [178]Kwiecinski A,Nowak P.Effect of prenatal manganese intoxication on [(3)H]glucose uptake in the brain of rats lesioned:as neonates with 6-hydroxydopamine. Pharmacol Rep,2009,61(3):558-563.
    [179]Cheatham B. Insulin Action and the Insulin Signaling Network. Endocr Rev,1995,16(2):117-142.
    [180]Lee J, Pilch PF. The insulin receptor:structure, function, and signaling. Am J Physiol,266:c319-c334.
    [181]王涤非,蔡冬梅,蒋丽娟等.老年胰岛素抵抗小鼠骨骼肌细胞磷脂酰肌醇-3激酶的表达.中国现代医学杂志,2006,16(10):1498-1500.
    [182]王艳军PI3K、P70S6K在胰岛素抵抗大鼠脂肪中的表达及其意义.中国老年学杂志,2008,28:559-562.
    [183]王雨裱,孙佳犄,刘毓敏.人参皂苷对胰岛素抵抗大鼠模型中GLUT4和PI3K表达的影响.辽宁中医药大学学报,2009,11:231-236.
    [184]徐天娇,袁秉祥.胰岛素与硒联合作用糖尿病大鼠骨骼肌胰岛素信号转导通路中PI3K和GLUT4蛋白的.中国组织工程研究与临床康复,2010,14(7):1213-1218.
    [185]Frosig C, Sajan MP, Maarbjerg SJ,et al. Exercise improves phosphatidylinositol-3,4,5-trisphosphate responsiveness of atypical protein kinase C and interacts with insulin signalling to peptide elongation in human skeletal muscle. J Physiol,2007,582(3):1289-1301.
    [186]Wojtaszewski JF, Nielsen JN, Richter EA. Invited review:effect of acute exercise on insulin signaling and action in humans. J Appl Physiol,2002,93 (1):384-392.
    [187]Drake PG, Posner BI.Insulin receptor-associated protein tyrosine phosphatase(s):role in insulin action. Mol Cell Biochem,1998, 182(1-2):79-89.
    [188]Goldstein BJ. Protein-tyrosine phosphatases:emerging targets for therapeutic intervention in type 2 diabetes and related states of insulin resistance. J Clin Endocrinol Metab,2002,87(6):2474-2480.
    [189]Goldstein BJ, Bittner-Kowalczyk A, White MF, et al. Tyrosine dephosphorylation and deactivation of insulin receptor substrate-1 by protein-tyrosine phosphatase 1B. Possible facilitation by the formation of a ternary complex with the Grb2 adaptor protein. J Biol Chem,2000,275(6):4283-4289.
    [190]Thareja S, Aggarwal S, Bhardwaj TR,et al. Protein tyrosine phosphatase 1B inhibitors:A molecular level legitimate approach for the management of diabetes mellitus. Medicinal Research Reviews, n/a. doi:10.1002/med.20219.
    [191]Elchebly M, Payette P, Michaliszyn E, et al. Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. Science,1999,283(5407):1544-1548.
    [192]Goldstein BJ, Ahmad F, Ding W, Li PM,et al. Regulation of the insulin signalling pathway by cellular protein-tyrosine phosphatases. Mol Cell Biochem,1998,182(1-2):91-99.
    [193]Klaman LD,Boss O, Peroni OD,et al. Increased energy expenditure, decreased adiposity, and tissue-specific insulin sensitivity in protein-tyrosine phosphatase 1B-deficient mice. Mol Cell Biol,2000,20(15):5479-5489.
    [194]Gum RJ, Gaede LL,Koterski SL,et al. Reduction of protein tyrosine phosphatase 1B increases insulin-dependent signaling in ob/ob mice. Diabet,2003,52(1):21-28.
    [195]Zinker BA, Rondinone CM, Trevillyan JM,et al. PTP1B antisense oligonucleotide lowers PTP1B protein,normalizes blood glucose, and improves insulin sensitivity in diabetic mice. Proc Natl Acad Sci USA,2002,99 (17):11357-11362.
    [196]Di PR, Frittitta L, Miscio G, et al. A variation in 3'UTR of hPTP1B increases specific gene expression and associates with insulin resistance. Am J Hum Genet,2002,70(3):806-812.
    [197]Xue B, Kim YB, Lee A, et al. Protein-tyrosine phosphatase 1B deficiency reduces insulin resistance and the diabetic phenotype in mice with polygenic insulin resistance. J Biol Chem,2007,282 (33):23829-23840.
    [198]Medeiros C, Frederico MJ, Luz GD, et al. Exercise training reduces insulin resistance and up regulates the mTOR/p70S6k pathway in cardiac muscle of diet-induced obesity rats.J Cell Physiol,2010,226 (3):666-674.
    [199]Ropelle ER, Pauli JR, Prada PO, et al. Reversal of diet-induced insulin resistance with a single bout of exercise in the rat:the role of PTP1B and IRS-1 serine phosphorylation. J Physiol,2006,577(3):997-1007.
    [200]张明军.RBP4对游泳训练大鼠脂肪细胞IR和IRS_1蛋白表达和磷酸化的影响.天津体育学院学报,2010,25(1):38-40.
    [201]Vidal-Puig A,O'Rahilly S. Controlling the glucose factory. Nature,2001,413:125-126.
    [202]Nordlie RC, Foster JD. Regulation of glucose production by the liver. Annu Rev Nutr,1999, (19):379-406.
    [203]张均田.现代药理实验方法.北京:北京医科大学、协和医科大学联合出版社,1997:984-985.
    [204]龚明,肖谦.脂联素对大鼠肝细胞葡萄糖激酶与酸烯醇式丙酮酸羧激酶活性影响的研究.重庆医科大学报,2005,30(4):567-569.
    [205]DeFronzo RA. The triumvirate:beta-cell, muscle, liver:a collusion responsible for NIDDM. Diabet,1988,37:667-687.
    [206]Bogardus C, Lillioja S,Howard BV. Relationships between insulin secretion, insulin action, and fasting plasma glucose concentration in nondiabetic and noninsulin-dependent diabetic subjects. J Clin Invest,1984,74:1238-1246.
    [207]Patricia Iozzo KH, Oikonen V. Insulin-Mediated Hepatic Glucose Uptake Is Impaired in Type 2 Diabetes:Evidence for a Relationship with Glycemic Control. J Clin Endocr,2003,88:2055-2060.
    [208]Beringer A, Thaler H.On quantitative analyses of the glycogen content of the liver in normal and sick persons. Wien Klin Wochenschr,1963,26:509-513.
    [209]Martin Krssak AB, Bernroider E. Alterations in Postprandial Hepatic Glycogen Metabolism in Type 2 Diabetes. Diabet,2004,53:3048-3056.
    [210]Parsa R, Bossard P. Induction of the glucokinase gene by insulin in cultured neonatal rat hepatocytes. Eur J Biochem,1996,236(15): 214-221.
    [211]Hanson RW. Regulation of phosphoenolpyruvate carboxykinase (GTP) gene expression. Annu Rev Biochem,1997,66:581-611.
    [212]Sun Y, Liu S, Ferguson S.Phosphoenolpyruvate Carboxykinase Overexpression Selectively Attenuates Insulin Signaling and Hepatic Insulin Sensitivity in Transgenic Mice. J Bio,2002,277:23301-23307.
    [213]Shin DJ, Odom DP, Scribner KB, et al. Retinoid regulation of the phosphoenolpyruvate carboxykinase gene in liver. Molec Cell Endocri,2002,195:39-54.
    [214]李焱,何娟,李芳萍.抵抗素在肝脏胰岛素抵抗中的作用及其机制.中国病理生 理杂志,2009,25:688-69

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