不同脂肪高脂日粮诱发胰岛素抵抗综合征大鼠模型的特性研究
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摘要
目的国内外流行病学调查和实验研究已证实,高脂饮食是诱发胰岛素抵抗综合征(IRS)的重要环境因素,但不同脂肪在IRS发生过程中所起的作用可能不同。本实验拟通过给予大鼠相同脂肪含量、不同脂肪的饮食,分析猪油、豆油、氢化椰子油、乳脂4种不同脂肪的高脂日粮对大鼠血液生化指标动态变化趋势、胰岛素敏感性、脏器损伤、脂联素血清含量及其在脂肪组织中mRNA表达水平的影响。
方法40只雄性SD大鼠随机分为5组,其中对照组给予普通日粮,4个高脂组分别给予脂肪热量比相同的猪油、豆油、氢化椰子油、乳脂高脂日粮。喂养6周,每两周测定空腹血糖、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-c)、总胆固醇(TC)、胰岛素,根据胰岛素敏感性指数(ISI)=㏑ 1/( FPG×FINS)评定大鼠的胰岛素敏感性,6周后取肝脏、胰腺、心脏做切片,观察肝脏、胰岛、冠状动脉的损伤情况,并取肾周脂肪测定脂联素mRNA的表达。
结果
1.高脂组平均日饲料消耗量以氢化椰子油组最多、猪油组最少,实验末,乳脂组大鼠体重最高、猪油组最低;
2.各组血糖均呈上升趋势,但变化情况不同,第15天时豆油组测定值显著低于对照组(P﹤0.05);
3.整个实验过程中高脂组血清TG均低于对照组,第15天时氢化椰子油组测定值显著低于对照组(P﹤0.05),实验末,乳脂组显著高于其它高脂组(P﹤0.05);
4.高脂组血清HDL-c均呈下降趋势,从15天开始高脂组均显著低于对照组(P﹤0.05)并以豆油组下降幅度最大;
5.各高脂组血清胰岛素呈上升趋势,但变化情况不同,而对照组呈下降趋势,实验末,猪油组、乳脂组、豆油组均显著高于对照组(P﹤0.05);
6.各实验组ISI均呈下降趋势,但高脂组下降更快,29天时乳脂组已经显著低于对照组(P﹤0.05),实验末,猪油组、乳脂组均显著低于对照组(P﹤0.05);
7.整个实验过程中各组间血清总胆固醇没有明显差异;
8.高脂组均出现肝细胞灶性坏死、局部炎细胞浸润、较多的空泡,但各组间无明显损伤差异;而各实验组均未发现胰岛、心脏冠状动脉的组织结构损伤;
9.高脂组血清脂联素含量均下降,并以乳脂组下降最大,豆油组下降最小,但与对照组无明显差异(P>0.05),其中氢化椰子油组血清脂联素与HDL-c、TG、TC呈正相关性,相关系数分别为(r=0.784,p=0.021;r=0.768,p=0.026;r=0.949,p=0.0003),猪油组血清脂联素与血糖、体重呈负相关性,相关系数分别为(r=-0.742,p=0.035;r=-0.721,p=0.044);
10.高脂组肾周脂肪组织脂联素mRNA表达水平与对照组无明显差异。
结论
1.四种高脂日粮诱发IRS大鼠模型的综合效果依次为乳脂、猪油、豆油、氢化椰子油;
2.高乳脂摄入导致大鼠最高的血清甘油三酯、血糖及体重;
3.高猪油摄入导致大鼠最高的血清胰岛素水平,最低的胰岛素敏感性,但该组能量摄入量最少、体重最低,该组的血清脂联素与血糖、体重呈负相关性;
4.高豆油摄入导致大鼠最低的血清HDL-c、血糖,短期内能刺激胰岛素显著上升而后又下降;
5.高氢化椰子油摄入,短期内能刺激TG显著下降而后又上升,该组的血清脂联素与HDL-c、TG、TC呈正相关性;
6.高脂饮食在短时间内不会引起大鼠空腹血糖、血清总胆固醇显著升高;
7.高脂饮食首先对大鼠肝脏造成损伤,表现为肝细胞灶性坏死、局部炎细胞浸润、出现较多的空泡,但短期内对胰岛和冠状动脉无明显损伤;
8.高脂饮食导致大鼠血清脂联素含量降低,但短时间内对大鼠肾周脂肪组织脂联素mRNA表达水平没有影响。
Objective Previous studies have indicated that the development of insulin resistance syndrome(IRS) were closely related to high-fat diets.The particular type and source of dietary fat, however, may have its own impact on the characters of IRS.Rats were fed a series of high-fat diets, identical but for fat source: lard,bean oil,hydrogenated-coconut oil and butterfat. The influence of different diets on rats’blood biochemical parameters, insulin sensitivity index, hepatic、panceatic island、coronary artery scathe, adiponectin content in plasma and its mRNA express in adipose tissue were analyzed, which can provid reference for establishment and empirical study of this animal model.
Methods Forty 7-weeks-old healthy male SD rats assigned at random into five groups. The normal group was fed on standard laboratory chow(10.97% of calories as fat) and experimental groups were fed on isocaloric high fat diets(46.15% of calories as fat)for 6 weeks.Serum glucose(GLU), triglyeride(TG), HDL-cholesterol, cholesterol (CHO) and insulin were measured fortnightly interval. The insulin sensitivity was estimated by ISI index,ISI =㏑ 1/(FPG×FINS). At the end of the experiment, hepatic、panceatic island and coronary artery pathological examination was observed, moreover, the adiponectin mRNA expression was tested by RT-PCR.
Results
1. Hydrogenated-coconut oil group consumed the most chow,while lard group consumed the least; at the end, butterfat group were the heaviest of all groups, but lard group were the lightest;
2. The glucose level of all groups increased, but there was no obvious different among the five groups. The bean oil group had considerably lower glucose level compared with normal group on the 15th day(P﹤0.05);
3. Serum TG was significantly increased in butterfat group compared with other high-fat groups(P﹤0.05)in the end;
4. High-fat feeding groups exhibited obviously lower HDL-cholestero(lP﹤0.05) than normal group, especially the bean oil group;
5. Serum insulin increased in High-fat feeding groups,but normal group decreased. Moreover, it was significantly high in Lard、butterfat and bean oil groups compared with normal group(P﹤0.05)in the end;
6. As for ISI, butterfat group had been lower than normal group(P﹤0.05)since the 29th day, in addition, butterfat and lard groups were both lower than normal group(P﹤0.05)in the end;
7. However there were mild difference in TC among the five groups;
8. Hepatic was impaired in High-fat feeding groups including focalne necrosis, inflammatory cell infiltration and much vacuole; however,pancreatic islet and coronary artery were not impaired;
9. High-fat feeding groups exhibited lower adiponectin level than normal group especially the butterfat group;in Hydrogenated-coconut oil group,seruma adiponectin content was positively related to HDL-c(r=0.784,p=0.021)、TG (r=0.768,p=0.026)and TC(r=0.949,p=0.0003),while in Lard group it was negatively related to glucose(r=-0.742,p=0.035) and weigh(tr=-0.721,p=0.044);
10. There was no significant different in the adiponectin mRNA expression between high-fat feeding groups and normal group.
Conclusion
1. High butterfat chows had the best effect of the four high fat feeds on establishment of IRS rat model, and lard was better than bean oil, but hydrogenated-coconut oil was the worst;
2. High butterfat chows had the greatest sustained effect on TG , weight gain and glucose level;
3. High Lard chows appears to produce the greatest level of serum insulin, the lowest ISI, but this group has the lowest energy intake and weight, moreover seruma adiponectin level was negatively related to glucose and weight;
4. High Bean oil chows had the greatest effect on HDL-c and glucose, it could induce serum insulin significantly increased but decreased latter;
5. High Hydrogenated-coconut oil chows could induce serum insulin significantly decresed but increased latter, and seruma adiponectin level was positively related to HDL-c、TG and TC;
6. High-fat feeding did not induce fasting serum glucose and cholesterol of rat increased in 6 weeks;
7. Hepatic was impaired by high-fat feeding for 6 weeks; however,pancreatic islet and coronary artery were not impaired;
8. Serum adiponectin content decreased in rat fed with high-fat diet, but the mRNA expression level of adiponectin did not decrease .
方法40只雄性SD大鼠随机分为5组,其中对照组给予普通日粮,4个高脂组分别给予脂肪热量比相同的猪油、豆油、氢化椰子油、乳脂高脂日粮。喂养6周,每两周测定空腹血糖、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-c)、总胆固醇(TC)、胰岛素,根据胰岛素敏感性指数(ISI)=㏑ 1/( FPG×FINS)评定大鼠的胰岛素敏感性,6周后取肝脏、胰腺、心脏做切片,观察肝脏、胰岛、冠状动脉的损伤情况,并取肾周脂肪测定脂联素mRNA的表达。
结果
1.高脂组平均日饲料消耗量以氢化椰子油组最多、猪油组最少,实验末,乳脂组大鼠体重最高、猪油组最低;
2.各组血糖均呈上升趋势,但变化情况不同,第15天时豆油组测定值显著低于对照组(P﹤0.05);
3.整个实验过程中高脂组血清TG均低于对照组,第15天时氢化椰子油组测定值显著低于对照组(P﹤0.05),实验末,乳脂组显著高于其它高脂组(P﹤0.05);
4.高脂组血清HDL-c均呈下降趋势,从15天开始高脂组均显著低于对照组(P﹤0.05)并以豆油组下降幅度最大;
5.各高脂组血清胰岛素呈上升趋势,但变化情况不同,而对照组呈下降趋势,实验末,猪油组、乳脂组、豆油组均显著高于对照组(P﹤0.05);
6.各实验组ISI均呈下降趋势,但高脂组下降更快,29天时乳脂组已经显著低于对照组(P﹤0.05),实验末,猪油组、乳脂组均显著低于对照组(P﹤0.05);
7.整个实验过程中各组间血清总胆固醇没有明显差异;
8.高脂组均出现肝细胞灶性坏死、局部炎细胞浸润、较多的空泡,但各组间无明显损伤差异;而各实验组均未发现胰岛、心脏冠状动脉的组织结构损伤;
9.高脂组血清脂联素含量均下降,并以乳脂组下降最大,豆油组下降最小,但与对照组无明显差异(P>0.05),其中氢化椰子油组血清脂联素与HDL-c、TG、TC呈正相关性,相关系数分别为(r=0.784,p=0.021;r=0.768,p=0.026;r=0.949,p=0.0003),猪油组血清脂联素与血糖、体重呈负相关性,相关系数分别为(r=-0.742,p=0.035;r=-0.721,p=0.044);
10.高脂组肾周脂肪组织脂联素mRNA表达水平与对照组无明显差异。
结论
1.四种高脂日粮诱发IRS大鼠模型的综合效果依次为乳脂、猪油、豆油、氢化椰子油;
2.高乳脂摄入导致大鼠最高的血清甘油三酯、血糖及体重;
3.高猪油摄入导致大鼠最高的血清胰岛素水平,最低的胰岛素敏感性,但该组能量摄入量最少、体重最低,该组的血清脂联素与血糖、体重呈负相关性;
4.高豆油摄入导致大鼠最低的血清HDL-c、血糖,短期内能刺激胰岛素显著上升而后又下降;
5.高氢化椰子油摄入,短期内能刺激TG显著下降而后又上升,该组的血清脂联素与HDL-c、TG、TC呈正相关性;
6.高脂饮食在短时间内不会引起大鼠空腹血糖、血清总胆固醇显著升高;
7.高脂饮食首先对大鼠肝脏造成损伤,表现为肝细胞灶性坏死、局部炎细胞浸润、出现较多的空泡,但短期内对胰岛和冠状动脉无明显损伤;
8.高脂饮食导致大鼠血清脂联素含量降低,但短时间内对大鼠肾周脂肪组织脂联素mRNA表达水平没有影响。
Objective Previous studies have indicated that the development of insulin resistance syndrome(IRS) were closely related to high-fat diets.The particular type and source of dietary fat, however, may have its own impact on the characters of IRS.Rats were fed a series of high-fat diets, identical but for fat source: lard,bean oil,hydrogenated-coconut oil and butterfat. The influence of different diets on rats’blood biochemical parameters, insulin sensitivity index, hepatic、panceatic island、coronary artery scathe, adiponectin content in plasma and its mRNA express in adipose tissue were analyzed, which can provid reference for establishment and empirical study of this animal model.
Methods Forty 7-weeks-old healthy male SD rats assigned at random into five groups. The normal group was fed on standard laboratory chow(10.97% of calories as fat) and experimental groups were fed on isocaloric high fat diets(46.15% of calories as fat)for 6 weeks.Serum glucose(GLU), triglyeride(TG), HDL-cholesterol, cholesterol (CHO) and insulin were measured fortnightly interval. The insulin sensitivity was estimated by ISI index,ISI =㏑ 1/(FPG×FINS). At the end of the experiment, hepatic、panceatic island and coronary artery pathological examination was observed, moreover, the adiponectin mRNA expression was tested by RT-PCR.
Results
1. Hydrogenated-coconut oil group consumed the most chow,while lard group consumed the least; at the end, butterfat group were the heaviest of all groups, but lard group were the lightest;
2. The glucose level of all groups increased, but there was no obvious different among the five groups. The bean oil group had considerably lower glucose level compared with normal group on the 15th day(P﹤0.05);
3. Serum TG was significantly increased in butterfat group compared with other high-fat groups(P﹤0.05)in the end;
4. High-fat feeding groups exhibited obviously lower HDL-cholestero(lP﹤0.05) than normal group, especially the bean oil group;
5. Serum insulin increased in High-fat feeding groups,but normal group decreased. Moreover, it was significantly high in Lard、butterfat and bean oil groups compared with normal group(P﹤0.05)in the end;
6. As for ISI, butterfat group had been lower than normal group(P﹤0.05)since the 29th day, in addition, butterfat and lard groups were both lower than normal group(P﹤0.05)in the end;
7. However there were mild difference in TC among the five groups;
8. Hepatic was impaired in High-fat feeding groups including focalne necrosis, inflammatory cell infiltration and much vacuole; however,pancreatic islet and coronary artery were not impaired;
9. High-fat feeding groups exhibited lower adiponectin level than normal group especially the butterfat group;in Hydrogenated-coconut oil group,seruma adiponectin content was positively related to HDL-c(r=0.784,p=0.021)、TG (r=0.768,p=0.026)and TC(r=0.949,p=0.0003),while in Lard group it was negatively related to glucose(r=-0.742,p=0.035) and weigh(tr=-0.721,p=0.044);
10. There was no significant different in the adiponectin mRNA expression between high-fat feeding groups and normal group.
Conclusion
1. High butterfat chows had the best effect of the four high fat feeds on establishment of IRS rat model, and lard was better than bean oil, but hydrogenated-coconut oil was the worst;
2. High butterfat chows had the greatest sustained effect on TG , weight gain and glucose level;
3. High Lard chows appears to produce the greatest level of serum insulin, the lowest ISI, but this group has the lowest energy intake and weight, moreover seruma adiponectin level was negatively related to glucose and weight;
4. High Bean oil chows had the greatest effect on HDL-c and glucose, it could induce serum insulin significantly increased but decreased latter;
5. High Hydrogenated-coconut oil chows could induce serum insulin significantly decresed but increased latter, and seruma adiponectin level was positively related to HDL-c、TG and TC;
6. High-fat feeding did not induce fasting serum glucose and cholesterol of rat increased in 6 weeks;
7. Hepatic was impaired by high-fat feeding for 6 weeks; however,pancreatic islet and coronary artery were not impaired;
8. Serum adiponectin content decreased in rat fed with high-fat diet, but the mRNA expression level of adiponectin did not decrease .
引文
[1]康艳明.代谢综合征的研究现状[J].内科,2008,3(10):22-103.
[2]杨金奎.代谢综合征新认识[J].中国社区医师,2006年第5期:6-8.
[3]张建,华琦.代谢综合征[M].第一版.北京:人民卫生出版社.2003.45– 130 .
[4] Tritos NA,Mantzoros.Syndrome of severe insulin resistance[J].Clin Endocrinol Metab,1998,83(9):3025-8.
[5]米杰,张力.胰岛素抵抗[J].中华预防医学杂志,2004,38(4):225-6.
[6] Grundy SM.Does a diagnosis of metabolic syndrome have value in clinical practice[J].Am J ClinNutr,2006,83:1248-51.
[7]杨永梅,张南雁.游离脂肪酸与糖尿病脂毒性作用[J].中国误诊学杂志,2003,3(1):48-51.
[8] DeFronzo RA. Dysfunctional fat cells, lipotoxicity and type 2 diabetes [J]. Int J Clin Pract,2004,143( Suppl):9-21.
[9] Lupi,Dotta F,Marselli L et al.Prolonged exposure to free fatty acids has cytostatic and pro-apoptotic effects on human pancreatic islets:evidence that beta–cell death is caspase mediated,partially dependent on ceramide pathway and Bcl-2 regulated[J].Diabetes,2002,51(5):1437–44.
[10] ATARU T,YOSHIKATSU N,MITSUO F, et al.Ultrasonographically assessed carotid at herosclerosis in Japanese type 2 diabetic patient s:role of nonesterified fatty acids[J].Metabolism,2002,51 (5):539-543.
[11] Fueger P T, Bracy D P, Malabanan C M, et al. HexokinaseⅡover expression improves exercise-stimulated but not insulin-stimu-lated muscle glucose up take in high-fat-fed C57BL /6J mice [J].D iabetes, 2004, 53: 306 - 14.
[12] Youngren J F, Paik J, Barnard R J. Impaired insulin-receptor au- tophosphorylation is an early defect in fat-fed, insulin-resistant rats[J]. J.Physiol, 2001, 91: 2240–7.
[13] Mithieux G, Guignot L, Bordet J C, et al. Intrahepatic mecha-nisms underlying the effect of metformin in decreasing basal glucose production in rats fed a high-fat diet[J].D iabetes, 2002,51:139– 43.
[14] MAN Z W,HIRASHIMA T,MORI S,et al.Decrease in triglyceride accumulation in tissues by restricted diet and improvement of diabetes in Otsuka Long-Evans Tokush-ima fatty rats, a non-insulin-dependent diabetes model[J].Metabolism, 2000,49(1):108-114.
[15] Gerald I. Shulman. Cellular mechanisms of insulin resistance[J].The Journal of Clinical Investigation ,2000,106(2):170-6.
[16]卜石,杨文英,王昕.脂毒性对大鼠胰岛细胞凋亡的作用[J].中华糖尿病杂志.2004, 12(6):433-436.
[17] INOGUCHI T , LI P , UMEDA F , et al. High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C-dependent activation of NAD (P) Hoxidase in cultured vascular cells[J]. Diabetes,2000,49 (11):1939-45.
[18] Hu FB, van Dam RM, Liu S. Diet and risk of type II diabetes: the role of types of fat and carbohydrate[J]. Diabetolog,2001,44(7):805-817.
[19] Storlien LH , Jenkins AB , Chisholm DJ,et al. Influence of dietary fat composition on development of insulin resistance in rats. Relationship to muscle triglyceride and omega-3 fatty acids in muscle phospholipids [J].Diabetes,1991,40(2):280-289.
[20] Andrea S.Rossi, Yolanda B.Lombardo, Jean-Marc Lacorte,et al. Dietary fish oil positively regulates plasma leptin and adiponectin levels in sucrose-fed, insulin-resistant rats[J]. Am J Physiol Regul Integr Comp Physiol, 2005, 289:R486–94.
[21] Fasching P, Ratheiser K, Waldhausl W,et al. Metabolic effects of fish-oil supplementation in patients with impaire glucose tolerance[J]. Diabetes, 1991, 40: 583–589.
[22] Summers LK, Fielding BA, Bradshaw HA, et al. Substituting dietary saturated fat with Polyunsaturated fat changes abdominal fat distribution and improves insulin sensitivity[J]. Diabetolog, 2002,45(3):369-377.
[23] Fickova M, Hubert P, Cremel G, Leray C: Dietary(n-3)and(n-6) polyunsaturated fatty acids rapidly modify fatty acid composition and insulin effects in rat adipocytes [J]. J Nutr,1998, 128:512-519.
[24] Dubnov G, Berry EM. Polyunsaturated fatty acids, insulin resistance, and atherosclerosis: is inflammation the connecting link?[J]. Metabolic syndrome and related disoders, 2004,2(2):124-128.
[25] Marianne Haag, Nola G. Dippenaar. Dietary fats, fatty acids and insulin resistance: short reviews of a multifaceted connection[J].Med Sci Monit, 2005,11(12): 359-67.
[26] VESSBY B,UNSITUPA M,Hermansen K,etal.Substituting dietary saturated for minounsaturated fat impairs insulin sensitivity in healthy men and women:The KANWU Study[J].Diabetologia,2001,44(3):312-9.
[27]茅小燕,张爱珍.膳食脂肪、胰岛素抵抗与代谢综合征[J].国外医学:卫生学分册, 2006, 33(2): 73-76.
[28] Lau Dc,Dhillon B,Yah H,et a1.Adipokines:molecular links between obesity and atheroscleresis[J].Am J Physiol Heart Cite Physi, 2005, 288 (5):2031-2041.
[29] Smith U, Anderson cx, Gustafson B, et a1. Adipokines,systemic inflammationand inflamed adipose tissue in obesity and insulin rsistance [J]. International Congress Series,2007,1303(8):31-34.
[30] JING Yuan.HAN Jing,WU Jing,et a1.Effects of leptin on glycol- metabolism [J].Int J Pathol Clin Med,2007,27(5):434-37.
[31] Steppan CM,Bailey ST ,Bhat S,et al.The hormone resistin links obesity to diabetes[J].Nature,2001,409:307-12.
[32] Laza MA. How obesity causes diabetes:not a tall tale[J].Science, 2005, 307:373-5.
[33] Quon MJ.Reciprocal relationships between insulin resistance and endothelial dysfunction:Insights from therapeutic interventions[J].J Cent South Univ(Med Sci),2006,31(3):305-12.
[34]Kathy Jaworski,Maryam Ahmadian,et al.AdPLA ablation increases lipolysis and prevents obesity induced by high-fat feeding or leptin deficiency [J].Nature Medicine.2009,15,159-168 .
[35] Barry J,Goldstein,Rosario S.Adiponectin:a novel adipikine linking adipocytes and vascular function[J].J Clin Endocrinol Metab,2004,89: 2563-8.
[36] Bernhard I,Vitolds M,Andreas S,et al.Plasma adiponectin levels and sonographic phenotypes of subslinical carotid artery atherosclerosis data from the SAPHIR study[J].Stroke,2005,36(12):2577-82.
[37] Ling Li,Gangyi Yang,Qingming Li. High-Fat-and LiPid-Induced Insulin Resistancein Rats: The Comparison of Glucose Metabolism,Plasma Resistin and Adiponectin Levels[J]. Ann Nutr Metab 2006,50:499–505.
[38] Maho Sumiyoshi, Masahiro Sakanaka,Yoshiyuki Kimura.Chronic Intake of High-Fat and High-Sucrose Diets Differentially Affects Glucose Intolerance in Mice[J]. American Society for Nutrition,2006,136: 582-587.
[39]程海波,司晓晨,尚文斌,等.高脂饲料和高果糖餐分别诱导胰岛素抵抗大鼠模型的胰岛素敏感性[J].中国临床康复,2006,10(7):121-123.
[40]都健,曾芙蓉,赵玉岩,等.胰岛素抵抗大鼠血管内皮细胞的形态学变化[J].中华老年医学杂志,2005,24(7):541-543.
[41] Storlien L-H,James D-E,Burleigh K-M,etal. Fat feeding causes widespread in vivo insulin resistance,decreased energy expenditure,and obesity in rats[J].Am J Physiol,1986,251(5pt1):E576-83.
[42]张荣,许荣焜,许岭翎,等.高脂饲料诱导的大鼠胰岛素抵抗及其与血清瘦素的关系[J].基础医学与临床,2002,12(5):461-465.
[43] Yi LIU,Zongbao WANG,Weidong YIN,Qinkai, et al.Severe Insulin Resistance and Moderate Glomerulosclerosis in a Minipig Model Induced by High-Fat/High-Sucrose/High-Cholesterol Diet[J]. Exp.Anim. 2007, 56(1): 11-20.
[44]田爱平,郭赛珊,陈跃腾,等.高热量饲料诱发胰岛素抵抗动物模型的实验研究[J].中国药学杂志,2006,41(11):827-31.
[45] Chen C. Diurnal rhythms of glycogen metabolism in the liver and skeletal muscle in gold thioglucose-induced-obese mice with developing insulin resistanse[J].Obese.1992,16(11):913-921.
[46]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.
[47]卜石,杨文英,王昕等.长期高脂饲养对大鼠葡萄糖刺激的胰岛素分泌的影响[J].中华内分泌代谢杂志.2003,19(2):25-27.
[48]程海波,司晓晨.高果糖餐诱导实验性胰岛素抵抗综合征大鼠模型[J].南中医药大学学报,2006,22(1):31-34.
[49]艾静,王宁,杜杰,等.Wistar大鼠2型糖尿病动物模型的建立[J].中国药理学通报,2004,20(11):1309-1312.
[50]周宇,宋光耀,高宇,等.高糖、高饱和脂肪酸及高不饱和脂肪酸饮食对的老年大鼠胰岛素抵抗的影响[J].中国老年学杂志,2006,26(2):222-224.
[51] CHALKLEY S M,HETTIARACHCHI M,CHISHOLM D J,etal.Long-term high-fat feeding leads to severe insulin resistance but notdiabetes in Wistar rats [J ].Am J Physiol Endocrinol Metab, 2002,282 : E1231-E1238.
[52] Kharroubi I,Laurence L,Cardozo AK,etal.Free fatty acids and cytokines induce pancreatic -cell apoptosis by different mechanisms: role of nuclear factor-B and endoplasmic reticulum stress[J]. Endocrinol , 2004, 145(11): 5087-5096.
[53]茅小燕,张爱珍.膳食脂肪、胰岛素抵抗与代谢综合征[J].国外医学卫生学分册,2006,(33)2:73-76.
[54] Clarke SD.Polyunsaturated fatty acid regulation of gene transcription:a mechanism to improve energy balance and insulin resistance[J].Br J Nutr,2000,83(Suppl 1):s59-s66.
[55] Marshall JA,Bessessn DH,Hamman RF.High saturated fat and low starch and fiber are associated weth hyperinsulinaemia in a nondabetic population:the sanlu is valley diabetes study[J].Diabetologin, 1997,40(4):430-438.
[56] Scherer PE,Williams S, Fogliano M, et al. A novel serum p rotein similar to C1q, produced exclusively in adipocytes [J].J Biol Chem,1995, 270 (45) : 746 - 49.
[57] TakahashiM, Arita Y, Yamagata K, et al.Genomic structure and mutations in adipose-specific gene, adiponectin [J].Int J Obes RelatM etab D isord, 2000, 24 (7):861-68.
[58] Maeda N, Takahashi M, Funahashi T, et al. PPARgamma ligands expression and plasma concentrations of adiponectin, an adipose-derived protein[J]. 2001, 50 (9):2094-99.
[59]王佑民,左春林,王长江.高脂肪饮食对鼠脂联素mRNA表达的影响.安徽医科大学学报[J], 2003,38 (3):182-184.
[60] Liang Xi,Zhiyu Qian,Guanglin Xu, et al.Beneficial impact of crocetin, a carotenoid from saffron, on insulin sensitivity in fructose-fed rats[J].The Journal of Nutrional Biochemistry,2007,18(1):64-72.
[61] Andrea S. Rossi, Yolanda B. Lombardo, et al.Dietary fish oil positively regulates plasma leptin and adiponectin levels in sucrose-fed, insulin-resistant rats[J].Am J Physiol Regul Integr Comp Physiol,2005,289: R486–94.
[62] Milan G,Granzotto M,Scarda A, et al.Resistin and adiponectin expression in visceral fat of obese rats: effect of weight loss[J].Obes Res,2002,10(11): 1095-103.
[63] Carrie C. Coughlin, Brian N. Finck, et al.Effect of Marked Weight Loss on Adiponectin Gene Expression and Plasma Concentrations[J].OBESITY,(3): 640-645.
[64] Yamauchi T, Kamon J, Ito Y, et al. Cloning of adiponectin recep tors thatmediate antidiabetic metabolic effects[J]. N ature,2003, 423 (6 941) : 762 - 769.
[65] Berg A, Combs T, Scherer PE, et al. ACRP30/adiponectin: An adipokine regulating glucose and lipid metabolism[J].Trends Endocrinol Metab, 2002, 13(2): 84-89.
[66] Yamauchi T,Kamon J,Waki H,et al.The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity[J]. NatMed, 2001,7(8):941-46.
[67] Chinetti G, Zawadski C, Fruchart JC, et al. Expression of adiponectin receptors in human macrophages and regulation by agonists of the nuclear receptors PPAR gamma, and LXR [J].Biochem Biophys Res Comm un, 2004, 314 (1):151-58.
[68] Kharroubi I, Rasschaert J, Eizirik DL, et al. Exp ression of adiponectin receptors in pancreatic beta cells[J].Biochem Biophys Res Commun, 2003, 312(4):1118-22.
[69] Combs TP,Berg AH,Obici S,et al. Endogenous glucose production is inhibited by the adipose-derived protein Acrp 30 [J].J ClinInvest,2001,108: 1875- 81.
[70] Halleux CM,Takahashi M,Delporte ML,et al.Secretion of adiponectin and regulation of apM1 gene expression in human visceral adipose[J].Biophys Res Commun, 2001,288 (5):1102-07.
[71] Yoshio I,Tomohiro K,Kazuhiko I,et al.Hypoadiponectinemia is an independent risk factor for hypertension[J].Hypertension,2004,43:1318-23.
[72] Comuzzie AG, Funahashi T , Sonnenberg G, et al.The genetic basis of plasma variation in adiponectin , a global endophenotype for obesity and the metabolic syndrome[J].Clin Endocrinol Metab,2001,86:4321-25.
[2]杨金奎.代谢综合征新认识[J].中国社区医师,2006年第5期:6-8.
[3]张建,华琦.代谢综合征[M].第一版.北京:人民卫生出版社.2003.45– 130 .
[4] Tritos NA,Mantzoros.Syndrome of severe insulin resistance[J].Clin Endocrinol Metab,1998,83(9):3025-8.
[5]米杰,张力.胰岛素抵抗[J].中华预防医学杂志,2004,38(4):225-6.
[6] Grundy SM.Does a diagnosis of metabolic syndrome have value in clinical practice[J].Am J ClinNutr,2006,83:1248-51.
[7]杨永梅,张南雁.游离脂肪酸与糖尿病脂毒性作用[J].中国误诊学杂志,2003,3(1):48-51.
[8] DeFronzo RA. Dysfunctional fat cells, lipotoxicity and type 2 diabetes [J]. Int J Clin Pract,2004,143( Suppl):9-21.
[9] Lupi,Dotta F,Marselli L et al.Prolonged exposure to free fatty acids has cytostatic and pro-apoptotic effects on human pancreatic islets:evidence that beta–cell death is caspase mediated,partially dependent on ceramide pathway and Bcl-2 regulated[J].Diabetes,2002,51(5):1437–44.
[10] ATARU T,YOSHIKATSU N,MITSUO F, et al.Ultrasonographically assessed carotid at herosclerosis in Japanese type 2 diabetic patient s:role of nonesterified fatty acids[J].Metabolism,2002,51 (5):539-543.
[11] Fueger P T, Bracy D P, Malabanan C M, et al. HexokinaseⅡover expression improves exercise-stimulated but not insulin-stimu-lated muscle glucose up take in high-fat-fed C57BL /6J mice [J].D iabetes, 2004, 53: 306 - 14.
[12] Youngren J F, Paik J, Barnard R J. Impaired insulin-receptor au- tophosphorylation is an early defect in fat-fed, insulin-resistant rats[J]. J.Physiol, 2001, 91: 2240–7.
[13] Mithieux G, Guignot L, Bordet J C, et al. Intrahepatic mecha-nisms underlying the effect of metformin in decreasing basal glucose production in rats fed a high-fat diet[J].D iabetes, 2002,51:139– 43.
[14] MAN Z W,HIRASHIMA T,MORI S,et al.Decrease in triglyceride accumulation in tissues by restricted diet and improvement of diabetes in Otsuka Long-Evans Tokush-ima fatty rats, a non-insulin-dependent diabetes model[J].Metabolism, 2000,49(1):108-114.
[15] Gerald I. Shulman. Cellular mechanisms of insulin resistance[J].The Journal of Clinical Investigation ,2000,106(2):170-6.
[16]卜石,杨文英,王昕.脂毒性对大鼠胰岛细胞凋亡的作用[J].中华糖尿病杂志.2004, 12(6):433-436.
[17] INOGUCHI T , LI P , UMEDA F , et al. High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C-dependent activation of NAD (P) Hoxidase in cultured vascular cells[J]. Diabetes,2000,49 (11):1939-45.
[18] Hu FB, van Dam RM, Liu S. Diet and risk of type II diabetes: the role of types of fat and carbohydrate[J]. Diabetolog,2001,44(7):805-817.
[19] Storlien LH , Jenkins AB , Chisholm DJ,et al. Influence of dietary fat composition on development of insulin resistance in rats. Relationship to muscle triglyceride and omega-3 fatty acids in muscle phospholipids [J].Diabetes,1991,40(2):280-289.
[20] Andrea S.Rossi, Yolanda B.Lombardo, Jean-Marc Lacorte,et al. Dietary fish oil positively regulates plasma leptin and adiponectin levels in sucrose-fed, insulin-resistant rats[J]. Am J Physiol Regul Integr Comp Physiol, 2005, 289:R486–94.
[21] Fasching P, Ratheiser K, Waldhausl W,et al. Metabolic effects of fish-oil supplementation in patients with impaire glucose tolerance[J]. Diabetes, 1991, 40: 583–589.
[22] Summers LK, Fielding BA, Bradshaw HA, et al. Substituting dietary saturated fat with Polyunsaturated fat changes abdominal fat distribution and improves insulin sensitivity[J]. Diabetolog, 2002,45(3):369-377.
[23] Fickova M, Hubert P, Cremel G, Leray C: Dietary(n-3)and(n-6) polyunsaturated fatty acids rapidly modify fatty acid composition and insulin effects in rat adipocytes [J]. J Nutr,1998, 128:512-519.
[24] Dubnov G, Berry EM. Polyunsaturated fatty acids, insulin resistance, and atherosclerosis: is inflammation the connecting link?[J]. Metabolic syndrome and related disoders, 2004,2(2):124-128.
[25] Marianne Haag, Nola G. Dippenaar. Dietary fats, fatty acids and insulin resistance: short reviews of a multifaceted connection[J].Med Sci Monit, 2005,11(12): 359-67.
[26] VESSBY B,UNSITUPA M,Hermansen K,etal.Substituting dietary saturated for minounsaturated fat impairs insulin sensitivity in healthy men and women:The KANWU Study[J].Diabetologia,2001,44(3):312-9.
[27]茅小燕,张爱珍.膳食脂肪、胰岛素抵抗与代谢综合征[J].国外医学:卫生学分册, 2006, 33(2): 73-76.
[28] Lau Dc,Dhillon B,Yah H,et a1.Adipokines:molecular links between obesity and atheroscleresis[J].Am J Physiol Heart Cite Physi, 2005, 288 (5):2031-2041.
[29] Smith U, Anderson cx, Gustafson B, et a1. Adipokines,systemic inflammationand inflamed adipose tissue in obesity and insulin rsistance [J]. International Congress Series,2007,1303(8):31-34.
[30] JING Yuan.HAN Jing,WU Jing,et a1.Effects of leptin on glycol- metabolism [J].Int J Pathol Clin Med,2007,27(5):434-37.
[31] Steppan CM,Bailey ST ,Bhat S,et al.The hormone resistin links obesity to diabetes[J].Nature,2001,409:307-12.
[32] Laza MA. How obesity causes diabetes:not a tall tale[J].Science, 2005, 307:373-5.
[33] Quon MJ.Reciprocal relationships between insulin resistance and endothelial dysfunction:Insights from therapeutic interventions[J].J Cent South Univ(Med Sci),2006,31(3):305-12.
[34]Kathy Jaworski,Maryam Ahmadian,et al.AdPLA ablation increases lipolysis and prevents obesity induced by high-fat feeding or leptin deficiency [J].Nature Medicine.2009,15,159-168 .
[35] Barry J,Goldstein,Rosario S.Adiponectin:a novel adipikine linking adipocytes and vascular function[J].J Clin Endocrinol Metab,2004,89: 2563-8.
[36] Bernhard I,Vitolds M,Andreas S,et al.Plasma adiponectin levels and sonographic phenotypes of subslinical carotid artery atherosclerosis data from the SAPHIR study[J].Stroke,2005,36(12):2577-82.
[37] Ling Li,Gangyi Yang,Qingming Li. High-Fat-and LiPid-Induced Insulin Resistancein Rats: The Comparison of Glucose Metabolism,Plasma Resistin and Adiponectin Levels[J]. Ann Nutr Metab 2006,50:499–505.
[38] Maho Sumiyoshi, Masahiro Sakanaka,Yoshiyuki Kimura.Chronic Intake of High-Fat and High-Sucrose Diets Differentially Affects Glucose Intolerance in Mice[J]. American Society for Nutrition,2006,136: 582-587.
[39]程海波,司晓晨,尚文斌,等.高脂饲料和高果糖餐分别诱导胰岛素抵抗大鼠模型的胰岛素敏感性[J].中国临床康复,2006,10(7):121-123.
[40]都健,曾芙蓉,赵玉岩,等.胰岛素抵抗大鼠血管内皮细胞的形态学变化[J].中华老年医学杂志,2005,24(7):541-543.
[41] Storlien L-H,James D-E,Burleigh K-M,etal. Fat feeding causes widespread in vivo insulin resistance,decreased energy expenditure,and obesity in rats[J].Am J Physiol,1986,251(5pt1):E576-83.
[42]张荣,许荣焜,许岭翎,等.高脂饲料诱导的大鼠胰岛素抵抗及其与血清瘦素的关系[J].基础医学与临床,2002,12(5):461-465.
[43] Yi LIU,Zongbao WANG,Weidong YIN,Qinkai, et al.Severe Insulin Resistance and Moderate Glomerulosclerosis in a Minipig Model Induced by High-Fat/High-Sucrose/High-Cholesterol Diet[J]. Exp.Anim. 2007, 56(1): 11-20.
[44]田爱平,郭赛珊,陈跃腾,等.高热量饲料诱发胰岛素抵抗动物模型的实验研究[J].中国药学杂志,2006,41(11):827-31.
[45] Chen C. Diurnal rhythms of glycogen metabolism in the liver and skeletal muscle in gold thioglucose-induced-obese mice with developing insulin resistanse[J].Obese.1992,16(11):913-921.
[46]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.
[47]卜石,杨文英,王昕等.长期高脂饲养对大鼠葡萄糖刺激的胰岛素分泌的影响[J].中华内分泌代谢杂志.2003,19(2):25-27.
[48]程海波,司晓晨.高果糖餐诱导实验性胰岛素抵抗综合征大鼠模型[J].南中医药大学学报,2006,22(1):31-34.
[49]艾静,王宁,杜杰,等.Wistar大鼠2型糖尿病动物模型的建立[J].中国药理学通报,2004,20(11):1309-1312.
[50]周宇,宋光耀,高宇,等.高糖、高饱和脂肪酸及高不饱和脂肪酸饮食对的老年大鼠胰岛素抵抗的影响[J].中国老年学杂志,2006,26(2):222-224.
[51] CHALKLEY S M,HETTIARACHCHI M,CHISHOLM D J,etal.Long-term high-fat feeding leads to severe insulin resistance but notdiabetes in Wistar rats [J ].Am J Physiol Endocrinol Metab, 2002,282 : E1231-E1238.
[52] Kharroubi I,Laurence L,Cardozo AK,etal.Free fatty acids and cytokines induce pancreatic -cell apoptosis by different mechanisms: role of nuclear factor-B and endoplasmic reticulum stress[J]. Endocrinol , 2004, 145(11): 5087-5096.
[53]茅小燕,张爱珍.膳食脂肪、胰岛素抵抗与代谢综合征[J].国外医学卫生学分册,2006,(33)2:73-76.
[54] Clarke SD.Polyunsaturated fatty acid regulation of gene transcription:a mechanism to improve energy balance and insulin resistance[J].Br J Nutr,2000,83(Suppl 1):s59-s66.
[55] Marshall JA,Bessessn DH,Hamman RF.High saturated fat and low starch and fiber are associated weth hyperinsulinaemia in a nondabetic population:the sanlu is valley diabetes study[J].Diabetologin, 1997,40(4):430-438.
[56] Scherer PE,Williams S, Fogliano M, et al. A novel serum p rotein similar to C1q, produced exclusively in adipocytes [J].J Biol Chem,1995, 270 (45) : 746 - 49.
[57] TakahashiM, Arita Y, Yamagata K, et al.Genomic structure and mutations in adipose-specific gene, adiponectin [J].Int J Obes RelatM etab D isord, 2000, 24 (7):861-68.
[58] Maeda N, Takahashi M, Funahashi T, et al. PPARgamma ligands expression and plasma concentrations of adiponectin, an adipose-derived protein[J]. 2001, 50 (9):2094-99.
[59]王佑民,左春林,王长江.高脂肪饮食对鼠脂联素mRNA表达的影响.安徽医科大学学报[J], 2003,38 (3):182-184.
[60] Liang Xi,Zhiyu Qian,Guanglin Xu, et al.Beneficial impact of crocetin, a carotenoid from saffron, on insulin sensitivity in fructose-fed rats[J].The Journal of Nutrional Biochemistry,2007,18(1):64-72.
[61] Andrea S. Rossi, Yolanda B. Lombardo, et al.Dietary fish oil positively regulates plasma leptin and adiponectin levels in sucrose-fed, insulin-resistant rats[J].Am J Physiol Regul Integr Comp Physiol,2005,289: R486–94.
[62] Milan G,Granzotto M,Scarda A, et al.Resistin and adiponectin expression in visceral fat of obese rats: effect of weight loss[J].Obes Res,2002,10(11): 1095-103.
[63] Carrie C. Coughlin, Brian N. Finck, et al.Effect of Marked Weight Loss on Adiponectin Gene Expression and Plasma Concentrations[J].OBESITY,(3): 640-645.
[64] Yamauchi T, Kamon J, Ito Y, et al. Cloning of adiponectin recep tors thatmediate antidiabetic metabolic effects[J]. N ature,2003, 423 (6 941) : 762 - 769.
[65] Berg A, Combs T, Scherer PE, et al. ACRP30/adiponectin: An adipokine regulating glucose and lipid metabolism[J].Trends Endocrinol Metab, 2002, 13(2): 84-89.
[66] Yamauchi T,Kamon J,Waki H,et al.The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity[J]. NatMed, 2001,7(8):941-46.
[67] Chinetti G, Zawadski C, Fruchart JC, et al. Expression of adiponectin receptors in human macrophages and regulation by agonists of the nuclear receptors PPAR gamma, and LXR [J].Biochem Biophys Res Comm un, 2004, 314 (1):151-58.
[68] Kharroubi I, Rasschaert J, Eizirik DL, et al. Exp ression of adiponectin receptors in pancreatic beta cells[J].Biochem Biophys Res Commun, 2003, 312(4):1118-22.
[69] Combs TP,Berg AH,Obici S,et al. Endogenous glucose production is inhibited by the adipose-derived protein Acrp 30 [J].J ClinInvest,2001,108: 1875- 81.
[70] Halleux CM,Takahashi M,Delporte ML,et al.Secretion of adiponectin and regulation of apM1 gene expression in human visceral adipose[J].Biophys Res Commun, 2001,288 (5):1102-07.
[71] Yoshio I,Tomohiro K,Kazuhiko I,et al.Hypoadiponectinemia is an independent risk factor for hypertension[J].Hypertension,2004,43:1318-23.
[72] Comuzzie AG, Funahashi T , Sonnenberg G, et al.The genetic basis of plasma variation in adiponectin , a global endophenotype for obesity and the metabolic syndrome[J].Clin Endocrinol Metab,2001,86:4321-25.