鹅胰岛素信号途径3个相关基因的克隆及葡萄糖和胰岛素对其表达的影响
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摘要
胰岛素受体底物PH域相互作用蛋白(Pleckstrin homology domain-interacting protein. PHIP)是能促进GLUT4的移位,介导细胞的凋亡、增殖,在胰岛素诱导的信号转导途径中扮演重要的角色。而胰岛素受体底物1 (insulin receptor substrate 1, IRS1)和TBC区域家族成员1 (TBC (Tre-2/Bub2/Cdc16) domain family, member 1, TBC1D1)是胰岛素信号途径的关键基因,可能在PHIP实现对胰岛素信号途径调控的作用中起作用。本试验以四川白鹅肝脏组织为材料,扩增鹅PHIP、IRS1、TBC1D1基因mRNA部分序列,采用RACE技术扩增PHIP mRNA全序列,并运用实时定量PCR技术检测不同浓度葡萄糖、胰岛素处理鹅原代肝细胞对PHIP、IRS1、TBC1D1基因表达的影响。研究结果如下：
(1)克隆得到了四川白鹅IRS1和TBC1D1二个基因的部分编码区序列(Coding domain sequence, CDS),它们的大小分别为530bp和300bp。利用MEGA 5软件构建部分脊椎动物IRS1、TBC1D1基因的分子进化树发现,IRS1、TBC1D1基因的序列与火鸡、原鸡、斑胸草雀聚为一类。
(2)利用RACE技术扩增并获得PHIP基因3条mRNA剪接体全序列,分别长5,525bp、5,080bp和4,677bp,命名为PHIP-a、PHIP-b和PHIP-c。通过生物信息学分析3条鹅PHIP mRNA剪接体剪接方式为选择性加尾。
(3)鹅PHIP mRNA3种剪切体均编码相同蛋白质,由1295个氨基酸组成,蛋白相对分子量为147002.48Da,理论等电点pI=8.01。用NetPhos2.0软件预测发现有90个磷酸化位点,其中Ser位点60个,Thr位点18个,Tyr位点12个。用SMART在线软件分析发现有8个WD40区域,一个BROWO区域,5个Low complexity区域。
(4)在低浓度的葡萄糖组(5 mmol/L), PHIP、IRS1、TBC1D1三个基因的表达有所上调,在高浓度的葡萄糖组(30 mmol/L), PHIP、IRS1、TBC1D1三个基因的表达显著增加(P<0.05)；而低浓度的胰岛素诱导PHIP、IRS1、TBC1D1表达,当胰岛素浓度达到200 nmol/L时,PHIP、IRS1、TBC1D1的表达显著下降(P<0.05)。
(5)葡萄糖和胰岛素的协同作用发现,低浓度(50 nmol/L)的胰岛素和5 mmol/L和30 mmol/L协同葡萄糖都能促进PHIP、IRS1、TBC1DI个基因的表达,而高浓度胰岛素(100 nmol/L)在低糖和高糖协同下,都能显著抑制3个基因的表达。
The pleckstrin homology domain-interacting protein (PHIP) plays important roles in insulin-mediated signal transduction pathways, promotiong GLUT4 translocation and mediating cell apoptosis and proliferation. However, the IRS1 and TBC1D1 play essential roles in insulin signal pathway, and therefore these two genes are important to the insulin mediating signal pathway transduction. In the present study, IRS1 and TBC1D1 partial mRNA sequence of goose were cloned. And the full-lenth of PHIP mRNA sequence of goose was cloned using RACE technical.Then the different concentration of glucose and insulin were added to the medium of geese primary hepatocytes cultured in vitro, to investigate their roles on mRNA expression of PHIP, IRS1 and TBC1D1 using Real-Time RT-PCR. The results were as follows:
(1) The partial coding domain sequence (CDS) of IRS1, TBC1D1 genes were amplified by RT-PCR, and their length were 530bp and 300bp, respectively. The phylogenetic tree of IRS1 and TBCIDI gene in vertebrates were built using the MEGA 5.0 software, and results showed that the geese IRS1 and TBC1D1 gene have higher homology with that of Gallus, Turkey and Taenioygia guttata.
(2) Three alternatively spliced forms of PHIP mRNA were found by RACE technical, and named them as PHIP-a, PHIP-b and PHIP-c, respectively. The full-lenth of total three PHIP mRNA sequeces was 5,525bp,5,080bp and 4,677bp, respectively. In silicon analysis showed that the splicing mode of all three PHIP mRNA sequences was the selective termination.
(3) All the three splicing PHIP mRNA have the same CDS,encoding the same protein with 1295 amino acid. The relative molecular mass predicted is 147002.48Da, and the isoelectricpoint of PHIP protein was 8.01. PHIP amino acid sequence pocesses 90 phosphorylation-sites, including 60 Ser redidue,18 Thr redidue and 12 Tyr redidue. SMART online analysis suggested that PHIP protein possess eight WD40 domains, one browodomain and five low complexity domains.
(4) Comparing with control group,5 mmol/L glucose (low concentration)had tiny effects on promoting PHIP, IRS1 and TBC1D1 expression. Within 30 mmol/L glucose, the expression of PHIP, IRS1 and TBC1D1 were significantly increased (P<0.05).Low concentration of insulin could promote expression of PHIP, IRS1 and TBC1D1, while high concentration of insulin (200 nmol/L) could significantly decrease their expressions (P<0.05).
(5) When synergistic the effect of insulin and glucose, low concentration of insulin (50 nmol/L) with 5 mmol/L and 30 mmol/L glucose treatment could increase the expression of PHIP, IRS1 and TBC1D1. However, the high concentration of insulin (100 nmol/L) with both of the low and high concentrations of glucose could inhibit their expressions.
(1)克隆得到了四川白鹅IRS1和TBC1D1二个基因的部分编码区序列(Coding domain sequence, CDS),它们的大小分别为530bp和300bp。利用MEGA 5软件构建部分脊椎动物IRS1、TBC1D1基因的分子进化树发现,IRS1、TBC1D1基因的序列与火鸡、原鸡、斑胸草雀聚为一类。
(2)利用RACE技术扩增并获得PHIP基因3条mRNA剪接体全序列,分别长5,525bp、5,080bp和4,677bp,命名为PHIP-a、PHIP-b和PHIP-c。通过生物信息学分析3条鹅PHIP mRNA剪接体剪接方式为选择性加尾。
(3)鹅PHIP mRNA3种剪切体均编码相同蛋白质,由1295个氨基酸组成,蛋白相对分子量为147002.48Da,理论等电点pI=8.01。用NetPhos2.0软件预测发现有90个磷酸化位点,其中Ser位点60个,Thr位点18个,Tyr位点12个。用SMART在线软件分析发现有8个WD40区域,一个BROWO区域,5个Low complexity区域。
(4)在低浓度的葡萄糖组(5 mmol/L), PHIP、IRS1、TBC1D1三个基因的表达有所上调,在高浓度的葡萄糖组(30 mmol/L), PHIP、IRS1、TBC1D1三个基因的表达显著增加(P<0.05)；而低浓度的胰岛素诱导PHIP、IRS1、TBC1D1表达,当胰岛素浓度达到200 nmol/L时,PHIP、IRS1、TBC1D1的表达显著下降(P<0.05)。
(5)葡萄糖和胰岛素的协同作用发现,低浓度(50 nmol/L)的胰岛素和5 mmol/L和30 mmol/L协同葡萄糖都能促进PHIP、IRS1、TBC1DI个基因的表达,而高浓度胰岛素(100 nmol/L)在低糖和高糖协同下,都能显著抑制3个基因的表达。
The pleckstrin homology domain-interacting protein (PHIP) plays important roles in insulin-mediated signal transduction pathways, promotiong GLUT4 translocation and mediating cell apoptosis and proliferation. However, the IRS1 and TBC1D1 play essential roles in insulin signal pathway, and therefore these two genes are important to the insulin mediating signal pathway transduction. In the present study, IRS1 and TBC1D1 partial mRNA sequence of goose were cloned. And the full-lenth of PHIP mRNA sequence of goose was cloned using RACE technical.Then the different concentration of glucose and insulin were added to the medium of geese primary hepatocytes cultured in vitro, to investigate their roles on mRNA expression of PHIP, IRS1 and TBC1D1 using Real-Time RT-PCR. The results were as follows:
(1) The partial coding domain sequence (CDS) of IRS1, TBC1D1 genes were amplified by RT-PCR, and their length were 530bp and 300bp, respectively. The phylogenetic tree of IRS1 and TBCIDI gene in vertebrates were built using the MEGA 5.0 software, and results showed that the geese IRS1 and TBC1D1 gene have higher homology with that of Gallus, Turkey and Taenioygia guttata.
(2) Three alternatively spliced forms of PHIP mRNA were found by RACE technical, and named them as PHIP-a, PHIP-b and PHIP-c, respectively. The full-lenth of total three PHIP mRNA sequeces was 5,525bp,5,080bp and 4,677bp, respectively. In silicon analysis showed that the splicing mode of all three PHIP mRNA sequences was the selective termination.
(3) All the three splicing PHIP mRNA have the same CDS,encoding the same protein with 1295 amino acid. The relative molecular mass predicted is 147002.48Da, and the isoelectricpoint of PHIP protein was 8.01. PHIP amino acid sequence pocesses 90 phosphorylation-sites, including 60 Ser redidue,18 Thr redidue and 12 Tyr redidue. SMART online analysis suggested that PHIP protein possess eight WD40 domains, one browodomain and five low complexity domains.
(4) Comparing with control group,5 mmol/L glucose (low concentration)had tiny effects on promoting PHIP, IRS1 and TBC1D1 expression. Within 30 mmol/L glucose, the expression of PHIP, IRS1 and TBC1D1 were significantly increased (P<0.05).Low concentration of insulin could promote expression of PHIP, IRS1 and TBC1D1, while high concentration of insulin (200 nmol/L) could significantly decrease their expressions (P<0.05).
(5) When synergistic the effect of insulin and glucose, low concentration of insulin (50 nmol/L) with 5 mmol/L and 30 mmol/L glucose treatment could increase the expression of PHIP, IRS1 and TBC1D1. However, the high concentration of insulin (100 nmol/L) with both of the low and high concentrations of glucose could inhibit their expressions.
引文
[1]Yasuhara, M.,Ohama, T.,Matsuki, N.,et.al. Induction of Fatty Liver by Fasting in Suncus[J].Journal of lipid research,1991,32(6):887.
[2]Farhang-Fallah, J.,Randhawa, V. K.,Nimnual, A.,et.al. The Pleckstrin Homology (Ph) Domain-Interacting Protein Couples the Insulin Receptor Substrate 1 Ph Domain to Insulin Signaling Pathways Leading to Mitogenesis and Glut4 Translocation[J].Molecular and cellular biology,2002,22(20):7325.
[3]Koo, S. H.,Dutcher, A. K.,Towle, H. C. Glucose and Insulin Function through Two Distinct Transcription Factors to Stimulate Express of Lipogenic Enzyme Genes in Liver[J].Journal of Biological Chemistry,2001,276:9437-9445.
[4]Girard, J.,Foufelle, F. Mechanisms by Which Carbohydrates Regulate Express of Genes for Glylolytic and Lipogenic Enzymes [J].Annual review of mutrition,1997,17:325-352.
[5]Razzini, G.,Brancaccio, A.,Lemmon, M. A.,et.al The Role of the Pleckstrin Homology Domain in Membrane Targeting and Activation of Phospholipase C β 1[J].Journal of Biological Chemistry, 2000,275(20):14873.
[6]Farhang-Fallah, J.,Yin, X.,Trentin, G.,et.al. Cloning and Characterization of Phip, a Novel Insulin Receptor Substrate-1 Pleckstrin Homology Domaininteracting Protein[J].Journal of Biological Chemistry,2000,275(51):40492.
[7]Podcheko, A.,Northcott, P.,Bikopoulos, G.,et.al. Identification of a Wd40 Repeat-Containing Isoform of Phip as a Novel Regulator of {Beta}-Cell Growth and Survival[J].Molecular and cellular biology,2007,27(18):6484.
[8]Dhalluin, C.,Carlson, J. E.,Zeng, L.,et.al. Structure and Ligand of a Histone Acetyltransferase Bromodomain[J].Nature,1999,399(6735):491-496.
[9]Suganuma, T.,Pattenden, S. G.,Workman, J. L. Diverse Functions of Wd40 Repeat Proteins in Histone Recognition[J].Genes & development,2008,22(10):1265.
[10]Dyson,M. H.,Rose, S.,Mahadevan, L. C. Acetyllysine-Binding and Function of Bromodomain-Containing Proteins in Chromatin[J].Front Biosci,2001,6:D853-D865.
[11]Filetici, P.,Ornaghi, P.,Ballario, P. The Bromodomain:A Chromatin Browser[J].Front Biosci,2001,6: D866-D876.
[12]White, M. F. Irs Proteins and the Common Path to Diabetes[J].American Journal of Physiology-Endocrinology And Metabolism,2002,283(3):E413.
[13]Kaburagi, Y.,Satoh, S.,Yamamoto-Honda, R.,et.al. Insulin-Independent and Wortmannin-Resistant Targeting of Irs-3 to the Plasma Membrane Via Its Pleckstrin Homology Domain Mediates a Different Interaction with the Insulin Receptor from That of Irs-1[J].Diabetologia,2001,44(8): 992-1004.
[14]Steen, E.,Terry, B. M.,Rivera, E. J.,et.al. Impaired Insulin and Insulin-Like Growth Factor Expression and Signaling Mechanisms in Alzheimer's Disease-Is This Type 3 Diabetes?[J].Journal of Alzheimer's Disease,2005,7(1):63-80.
[15]Taouis, M.,Taylor, S. I.,Reitman, M. Cloning of the Chicken Insulin Receptor Substrate 1 Gene[J].Gene,1996,178(1-2):51-55.
[16]Danielsson, A.,st, A.,Lystedt, E.,et.al. Insulin Resistance in Human Adipocytes Occurs Downstream of Irsl after Surgical Cell Isolation but at the Level of Phosphorylation of Irsl in Type 2 Diabetes[J].FEBS Journal,2005,272(1):141-151.
[17]Dupont, J.,Tesseraud, S.,Simon, J. Insulin Signaling in Chicken Liver and Muscle[J].General and comparative endocrinology,2009,163(1-2):52-57.
[18]Toshiaki Fukushima.Toshiya Arai,Miyako Ariga-Nedachi,et al. Insulin Receptor Substrates Form High-Molecular-Mass Complexes That Modulate Their Availability to Insulin/Insulin-Like Growth Factor-Ⅰ Receptor Tyrosine Kinases[J].Biochemical and biophysical research communications,2011, 404:767-773.
[19]Gual, P.,Le Marchand-Brustel, Y.,Tanti, J. F. Positive and Negative Regulation of Insulin Signaling through Irs-1 Phosphorylation[J].Biochimie,2005,87(1):99-109.
[20]Kaburagi, Y.,Okochi, H.,Satoh, S. Role of Irs and Phip on Insulin-Induced Tyrosine Phosphorylation and Distribution of Irs Proteins[J].cell structure and function,2007,162:69-78.
[21]Manning, B. D.,Cantley, L. C. Akt/Pkb Signaling:Navigating Downstream[J].Cell,2007,129(7): 1261-1274.
[22]Pessin, J. E.,Saltiel, A. R. Signaling Pathways in Insulin Action:Molecular Targets of Insulin Resistance[J].Journal of Clinical Investigation,2000,106(2):165-170.
[23]Engelman, J. A.,Luo, J.,Cantley, L. C. The Evolution of Phosphatidylinositol 3-Kinases as Regulators of Growth and Metabolism[J].Nature Reviews Genetics,2006,7(8):606-619.
[24]Potapova, I. A.,El-Maghrabi, M. R.,Doronin, S. V.,et.al. Phosphorylation of Recombinant Human Atp:Citrate Lyase by Camp-Dependent Protein Kinase Abolishes Homotropic Allosteric Regulation of the Enzyme by Citrate and Increases the Enzyme Activity. Allosteric Activation of Atp:Citrate Lyase by Phosphorylated Sugars[J].Biochemistry,2000,39(5):1169-1179.
[25]Franke, T. F. Intracellular Signaling by Akt:Bound to Be Specific[J].Science signaling,2008,1(24): pe29.
[26]Dummler, B.,Hemmings, B. A. Physiological Roles of Pkb/Akt Isoforms in Development and Disease[J].Biochemical Society Transactions,2007,35(2):231-235.
[27]MacLean, P. S.,Zheng, D.,Jones, J. P.,et.al. Exercise-Induced Transcription of the Muscle Glucose Transporter (Glut 4) Gene[J].Biochemical and biophysical research communications,2002,292(2): 409-414.
[28]Gao, X.,Jin, C.,Xue, Y.,et.al. Computational Analyses of Tbc Protein Family in Eukaryotes[J].Protein and peptide letters,2008,15(5):505-509.
[29]Stone, S.,Abkevich, V.,Russell, D. L.,et.al. Tbcldl Is a Candidate for a Severe Obesity Gene and Evidence for a Gene/Gene Interaction in Obesity Predisposition[J].Human molecular genetics,2006, 15(18):2709.
[30]White, R. A.,Pasztor, L. M.,Richardson, P. M.,et.al. The Gene Encoding Tbcldl with Homology to the Tre-2/Usp6 Oncogene, Bub2, and Cdc16 Maps to Mouse Chromosome 5 and Human Chromosome 4[J].Cytogenetic and Genome Research,2000,89(3-4):272-275.
[31]Sakamoto, K.,Holman, G. D. Emerging Role for As160/Tbcld4 and Tbcldl in the Regulation of Glut4 Traffic[J].American Journal of Physiology-Endocrinology And Metabolism,2008,295(1): E29.
[32]Funai, K. Effects of in Vivo Exercise and in Vitro Contractile Activity on the Regulation of As160, Tbcldl and Glucose Transport in Rat Skeletal Muscle. The University of Michigan.2010
[33]E, A.,Zielak,Forde, N.,et.al. Identification of Novel Genes Associated with Dominant Follicle Development in Cattle[J].Vertebrate Reproductive Science & Technology 2007,19(8):967-975.
[34]Zhou, Q. L.,Jiang, Z. Y.,Holik, J.,et.al. Akt Substrate Tbcldl Regulates Glutl Expression through the Mtor Pathway in 3t3-L1 Adipocytes[J].The Biochemical journal,2008,411(3):647.
[35]Chadt, A.,Leicht, K.,Deshmukh, A.,et.al. Tbcldl Mutation in Lean Mouse Strain Confers Leanness and Protects from Diet-Induced Obesity[J].Nature genetics,2008,40(11):1354-1359.
[36]Koumanov, F.,Holman, G. D. Thrifty Tbcldl and Tbcld4 Proteins Link Signalling and Membrane Trafficking Pathways[J].Biochemical Journal,2007,403(Pt 2).
[37]Li, Shuai.,Francisco, A. B.,Han, C.,et.al. The Full-Length Isoform of the Mouse Pleckstrin Homology Domain-Interacting Protein (Phip) Is Required for Postnatal Growth[J].FEBS letters.
[38]Nosaka, T.,Kawashima, T.,Misawa, K.,et.al.'Stat5 as a Molecular Regulator of Proliferation, Differentiation and Apoptosis in Hematopoietic Cells[J].The EMBO journal,1999,18(17): 4754-4765.
[39]Onishi, M.,Nosaka, T.,Misawa, K.,et.al. Identification and Characterization of a Constitutively Active Stat5 Mutant That Promotes Cell Proliferation[J].Molecular and cellular biology,1998,18(7): 3871.
[40]Nogueira, V.,Park, Y.,Chen, C. C.,et.al. Akt Determines Replicative Senescence and Oxidative or Oncogenic Premature Senescence and Sensitizes Cells to Oxidative Apoptosis[J].Cancer Cell,2008, 14(6):458-470.
[41]Weber, I. T.,Fang, B.,Agniswamy, J. Caspases:Structure-Guided Design of Drugs to Control Cell Death[J].Mini Reviews in Medicinal Chemistry,2008,8(11):1154-1162.
[42]Fang, B.,Boross, P. I.,Tozser, J.,et.al. Structural and Kinetic Analysis of Caspase-3 Reveals Role for S5 Binding Site in Substrate Recognition[J].Journal of molecular biology,2006,360(3):654-666.
[43]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]. Journal of Clinical Investigation,1999, 103:253-260.
[44]KJ, L. Analysis of Relative Gene Expression Data Using Real-Time Quantitative Pcr and the 2(-Delta Delta C(T)) Method. [M].2001:402-408.
[45]Zeng, L.,Zhou, M. M. Bromodomain:An Acetyl-Lysine Binding Domain[J].FEBS letters,2002, 513(1):124-128.
[46]Davuluri, R. V.,Suzuki, Y.,Sugano, S.,et.al. The Functional Consequences of Alternative Promoter Use in Mammalian Genomes. [J].Trends in Genetics,2008,24:167-177.
[47]Aguirre, V.,Uchida, T.,Yenush, L.,et.al. The C-Jun Nh2-Terminal Kinase Promotes Insulin Resistance During Association with Insulin Receptor Substrate-1 and Phosphorylation of Ser307[J].Journal of Biological Chemistry,2000,275(12):9047.
[48]ChunChun, H.,JiWen, W.,LiAng, L.,et.al. The Role of Insulin and Glucose in Goose Primary Hepatocyte Triglyceride Accumulation[J].Journal of Experimental Biology,2009,212(10): 1553-1558.
[49]Bosco, D.,Costa, R.,Plastino, M.,et.al. Glucose Metabolism in the Idiopathic Blepharoptosis:Utility of the Oral Glucose Tolerance Test (Ogtt) and of the Insulin Resistance Index[J].Journal of the neurological sciences,2009,284(1-2):24-28.
[50]Valverde, A. M.,Kahn, C.,Beinborn, M. Insulin Signaling in Insulin Receptor Substrate(Irs)-1-Deficient Brown Adipocytes[J].Diabetes,1999,48(11):2122-2131.
[51]Carvalho, E.,Rondinone, C.,Smith, U. Insulin Resistance in Fat Cells from Obese Zucker Rats-Evidence for an Impaired Activation and Translocation of Protein Kinase B and Glucose Transporter 4.[J].Mol cell biochem,2000,206:7-16.
[52]Ide, T.,Shimano, H.,Yahagi, N.,et.al. Srebps Suppress Irs-2-Mediated Insulin Signalling in the Liver.[J]. Nat Cell Biol,2004,4(351-357).
[53]郝军,刘青娟,郑书深,等.不同浓度胰岛素对人肾小管上皮细胞SREBP-1, FAS表达及脂质形成的影响[J].中国病理生理杂志,26(007)：1275-1279.
[54]Halaas, J. L.,Gajiwala, K. S.,Maffei, M.,et.al. Weight-Reducing Effects of the Plasma Protein Encoded by the Obese Gene[J].Science,1995,269(5223):543.
[55]Yahagi, N.,Shimano, H.,Hasty, A. H.,et.al. Absence of Sterol Regulatory Element-Binding Protein-1 (Srebp-1) Ameliorates Fatty Livers but Not Obesity or Insulin Resistance Inlep Ob/Lep Ob Mice[J].Journal of Biological Chemistry,2002,277(22):19353.
[56]Horton, J. D.,Shah, N. A.,Warrington, J. A.,et.al. Combined Analysis of Oligonucleotide Microarray Data from Transgenic and Knockout Mice Identifies Direct Srebp Target Genes[J].Proceedings of the National Academy of Sciences of the United States of America,2003,100(21):12027.
[57]Shimomura, I.,Hammer, R. E.,Richardson, J. A.,et.al. Insulin Resistance and Diabetes Mellitus in Transgenic Mice Expressing Nuclear Srebp-lc in Adipose Tissue:Model for Congenital Generalized Lipodystrophy[J].Genes & development,1998,12(20):3182.
[58]向梳瑕.葡萄糖和胰岛素对鹅肝细胞内葡萄糖代谢平衡的研究[J].学位论文,雅安,四川农业大学,2010.
[59]Matsusue, K.,Kusakabe, T.,Noguchi, T., et.al. Hepatic Steatosis in Leptin-Deficient Mice Is Promoted by the Ppar [Gamma] Target Gene Fsp27[J].Cell Metabolism,2008,7(4):302-311.
[60]Dugan, M. E. R.,Aalhus, J. L.,Schaefer, A. L., et.al. The Effect of Conjugated Linoleic Acid on Fat to Lean Repartitioning and Feed Conversion in Pigs[J].Canadian journal of animal science,1997, 77(4):723-725.
[61]郝军,刘淑霞,刘青娟,等.胰岛素对人肾小管上皮细胞SREBP-1, FAS表达及脂质代谢的时效性研究[J].巾国药理学通报,2010,26(004)：517-521.
[62]韩春春,王继文,符自英,等.葡萄糖和胰岛素对鹅肝细胞脂肪酸合成酶活性及转录表达的影响[J].农业生物技术学报,2009,(004)：634-637.
[63]李翔,周圻,王玉莲,等.鹅肥肝形成机理的研究[J].动物科学与动物医学,2004,21(010)：32-34.
[64]Mourot, J.,Guy, G.,Lagarrigue, S., et.al. Role of Hepatic Lipogenesis in the Susceptibility to Fatty Liver in the Goose (Anser Anser)[J].Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology,2000,126(1):81-87.
[65]Yu ZW,Eriksson JW.The upregulating effect of insulin and vanadate on cell surface insulin receptors in rat adipocytes is modulated by glucose and energy availability.Horm Metab Res,2000,32:310-315.
[66]Pillay TS,Xiao S,Olefshy JM.Glucose-induced phosphorylation of the insulin receptor[J].J Clin Invest,1996,97:613-620.
[67]刘慧霞,李莉蓉.高糖对大鼠脂肪细胞胰岛素信号蛋白磷酸化的影响[J].中华内分泌代谢杂志,2002,18(005)：391-394.
[68]韩春春.不同因素诱导鹅肝细胞脂肪变性的机理研究[J].学位论文,雅安,四川农业大学,2010.
[69]Denechaud, P. D.,Bossard, P.,Lobaccaro, J. M. A., et.al. Chrebp, but Not Lxrs, Is Required for the Induction of Glucose-Regulated Genes in Mouse Liver[J].The Journal of clinical investigation,2008, 118(3):956.
[70]Sakiyama, H.,Wynn, R. M.,Lee, W. R., et.al. Regulation of Nuclear Import/Export of Carbohydrate Response Element-Binding Protein (Chrebp):Interaction of an A-Helix of Chrebp with the 14-3-3 Proteins and Regulation by Phosphorylation[J].The Journal of biological chemistry,2008,283(36): 24899-24908.
[71]Uyeda, K.,Yamashita, H.,Kawaguchi, T. Carbohydrate Responsive Element-Binding Protein (Chrebp):A Key Regulator of Glucose Metabolism and Fat Storage[J].Biochemical pharmacology, 2002,63(12):2075-2080.
[72]Mitro, N.,Mak, P. A.,Vargas, L., et.al. The Nuclear Receptor Lxr Is a Glucose Sensor[J].Nature, 2006,445(7124):219-223.
[73]Danilova, O. V.,Tai, A. K.,Mele, D. A., et.al. Neurogenin 3-Specific Dipeptidyl Peptidase-2 Deficiency Causes Impaired Glucose Tolerance, Insulin Resistance, and Visceral Obesity[J].Endocrinology,2009,150(12):5240.
[74]Haus, J. M.,Solomon, T. P. J.,Marchetti, C. M., et.al. Free Fatty Acid-Induced Hepatic Insulin Resistance Is Attenuated Following Lifestyle Intervention in Obese Individuals with Impaired Glucose Tolerance[J]. Journal of Clinical Endocrinology & Metabolism,2010,95(1):323.
[75]Foufelle, F.,Ferre, P. New Perspectives in the Regulation of Hepatic Glycolytic and Lipogenic Genes by Insulin and Glucose:A Role for the Transcription Factor Sterol Regulatory Element Binding Protein-1c[J].Biochemical Journal,2002,366-377.
[76]Koo, S. H.,Dutcher, A. K.,Towle, H. C. Glucose and Insulin Function through Two Distinct Transcription Factors to Stimulate Expression of Lipogenic Enzyme Genes in Liver[J].Journal of Biological Chemistry,2001,276(12):9437.
[77]Li, M.,Youngren, J. F.,Dunaif, A.,et.al. Decreased Insulin Receptor (Ir) Autophosphorylation in Fibroblasts from Patients with Pcos:Effects of Serine Kinase Inhibitors and Ir Activators[J].Journal of Clinical Endocrinology & Metabolism,2002,87(9):4088.
[78]Tirosh, A.,Potashnik, R.,Bashan, N., et.al. Oxidative Stress Disrupts Insulin-Induced Cellular Redistribution of Insulin Receptor Substrate-1 and Phosphatidylinositol 3-Kinase in 3t3-L1 Adipocytes. A Putative Cellular Mechanism for Impaired Protein Kinase B Activation and Glut4 Translocation[J].The Journal of biological chemistry,1999,274(15):10595.
[79]刘慧霞,何碧秀,陈碧莲,等.高胰岛素和高糖对大鼠脂肪细胞胰岛素信号蛋白的影响[J].中国糖尿病杂志,2003,11(002)：118-121.
[80]Tanti, J. F.,Gremeaux, T.,Grillo, S., et.al. Overexpression of a Constitutively Active Form of Phosphatidylinositol 3-Kinase Is Sufficient to Promote Glut 4 Translocation in Adipocytes[J].Journal of Biological Chemistry,1996,271(41):25227.
[81]Pillay, T. S.,Xiao, S.,Olefsky, J. M. Glucose-Induced Phosphorylation of the Insulin Receptor. Functional Effects and Characterization of Phosphorylation Sites[J].Journal of Clinical Investigation, 1996,97(3):613.
[82]Jian-Xiong, L.,Fen-Fen, C.,Gong-She, Y. Effect of Insulin on Transcription of Lipogenic and Lipolytic-Related Genes and Lipid Metabolism in Primary Porcine Adipocytes[J].Chinese Journal of Agricultural Biotechnology,2006,3(02):135-140.
[83]Foufelle, F.,Lepetit, N.,Bosc, D., et.al. Dnase I Hypersensitivity Sites and Nuclear Protein Binding on the Fatty Acid Synthase Gene:Identification of an Element with Properties Similar to Known Glucose-Responsive Elements[J].Biochemical Journal,1995,308(Pt 2):521.
[84]Choi, S. S.,Diehl, A. M. Hepatic Triglyceride Synthesis and Nonalcoholic Fatty Liver Disease[J].Current opinion in lipidology,2008,19(3):295.
[85]Decaux, J. F.,Marcillat, O.,Pichard, A. L., et.al. Glucose-Dependent and-Independent Effect of Insulin on Gene Expression[J].Journal of Biological Chemistry,1991,266(6):3432.
[2]Farhang-Fallah, J.,Randhawa, V. K.,Nimnual, A.,et.al. The Pleckstrin Homology (Ph) Domain-Interacting Protein Couples the Insulin Receptor Substrate 1 Ph Domain to Insulin Signaling Pathways Leading to Mitogenesis and Glut4 Translocation[J].Molecular and cellular biology,2002,22(20):7325.
[3]Koo, S. H.,Dutcher, A. K.,Towle, H. C. Glucose and Insulin Function through Two Distinct Transcription Factors to Stimulate Express of Lipogenic Enzyme Genes in Liver[J].Journal of Biological Chemistry,2001,276:9437-9445.
[4]Girard, J.,Foufelle, F. Mechanisms by Which Carbohydrates Regulate Express of Genes for Glylolytic and Lipogenic Enzymes [J].Annual review of mutrition,1997,17:325-352.
[5]Razzini, G.,Brancaccio, A.,Lemmon, M. A.,et.al The Role of the Pleckstrin Homology Domain in Membrane Targeting and Activation of Phospholipase C β 1[J].Journal of Biological Chemistry, 2000,275(20):14873.
[6]Farhang-Fallah, J.,Yin, X.,Trentin, G.,et.al. Cloning and Characterization of Phip, a Novel Insulin Receptor Substrate-1 Pleckstrin Homology Domaininteracting Protein[J].Journal of Biological Chemistry,2000,275(51):40492.
[7]Podcheko, A.,Northcott, P.,Bikopoulos, G.,et.al. Identification of a Wd40 Repeat-Containing Isoform of Phip as a Novel Regulator of {Beta}-Cell Growth and Survival[J].Molecular and cellular biology,2007,27(18):6484.
[8]Dhalluin, C.,Carlson, J. E.,Zeng, L.,et.al. Structure and Ligand of a Histone Acetyltransferase Bromodomain[J].Nature,1999,399(6735):491-496.
[9]Suganuma, T.,Pattenden, S. G.,Workman, J. L. Diverse Functions of Wd40 Repeat Proteins in Histone Recognition[J].Genes & development,2008,22(10):1265.
[10]Dyson,M. H.,Rose, S.,Mahadevan, L. C. Acetyllysine-Binding and Function of Bromodomain-Containing Proteins in Chromatin[J].Front Biosci,2001,6:D853-D865.
[11]Filetici, P.,Ornaghi, P.,Ballario, P. The Bromodomain:A Chromatin Browser[J].Front Biosci,2001,6: D866-D876.
[12]White, M. F. Irs Proteins and the Common Path to Diabetes[J].American Journal of Physiology-Endocrinology And Metabolism,2002,283(3):E413.
[13]Kaburagi, Y.,Satoh, S.,Yamamoto-Honda, R.,et.al. Insulin-Independent and Wortmannin-Resistant Targeting of Irs-3 to the Plasma Membrane Via Its Pleckstrin Homology Domain Mediates a Different Interaction with the Insulin Receptor from That of Irs-1[J].Diabetologia,2001,44(8): 992-1004.
[14]Steen, E.,Terry, B. M.,Rivera, E. J.,et.al. Impaired Insulin and Insulin-Like Growth Factor Expression and Signaling Mechanisms in Alzheimer's Disease-Is This Type 3 Diabetes?[J].Journal of Alzheimer's Disease,2005,7(1):63-80.
[15]Taouis, M.,Taylor, S. I.,Reitman, M. Cloning of the Chicken Insulin Receptor Substrate 1 Gene[J].Gene,1996,178(1-2):51-55.
[16]Danielsson, A.,st, A.,Lystedt, E.,et.al. Insulin Resistance in Human Adipocytes Occurs Downstream of Irsl after Surgical Cell Isolation but at the Level of Phosphorylation of Irsl in Type 2 Diabetes[J].FEBS Journal,2005,272(1):141-151.
[17]Dupont, J.,Tesseraud, S.,Simon, J. Insulin Signaling in Chicken Liver and Muscle[J].General and comparative endocrinology,2009,163(1-2):52-57.
[18]Toshiaki Fukushima.Toshiya Arai,Miyako Ariga-Nedachi,et al. Insulin Receptor Substrates Form High-Molecular-Mass Complexes That Modulate Their Availability to Insulin/Insulin-Like Growth Factor-Ⅰ Receptor Tyrosine Kinases[J].Biochemical and biophysical research communications,2011, 404:767-773.
[19]Gual, P.,Le Marchand-Brustel, Y.,Tanti, J. F. Positive and Negative Regulation of Insulin Signaling through Irs-1 Phosphorylation[J].Biochimie,2005,87(1):99-109.
[20]Kaburagi, Y.,Okochi, H.,Satoh, S. Role of Irs and Phip on Insulin-Induced Tyrosine Phosphorylation and Distribution of Irs Proteins[J].cell structure and function,2007,162:69-78.
[21]Manning, B. D.,Cantley, L. C. Akt/Pkb Signaling:Navigating Downstream[J].Cell,2007,129(7): 1261-1274.
[22]Pessin, J. E.,Saltiel, A. R. Signaling Pathways in Insulin Action:Molecular Targets of Insulin Resistance[J].Journal of Clinical Investigation,2000,106(2):165-170.
[23]Engelman, J. A.,Luo, J.,Cantley, L. C. The Evolution of Phosphatidylinositol 3-Kinases as Regulators of Growth and Metabolism[J].Nature Reviews Genetics,2006,7(8):606-619.
[24]Potapova, I. A.,El-Maghrabi, M. R.,Doronin, S. V.,et.al. Phosphorylation of Recombinant Human Atp:Citrate Lyase by Camp-Dependent Protein Kinase Abolishes Homotropic Allosteric Regulation of the Enzyme by Citrate and Increases the Enzyme Activity. Allosteric Activation of Atp:Citrate Lyase by Phosphorylated Sugars[J].Biochemistry,2000,39(5):1169-1179.
[25]Franke, T. F. Intracellular Signaling by Akt:Bound to Be Specific[J].Science signaling,2008,1(24): pe29.
[26]Dummler, B.,Hemmings, B. A. Physiological Roles of Pkb/Akt Isoforms in Development and Disease[J].Biochemical Society Transactions,2007,35(2):231-235.
[27]MacLean, P. S.,Zheng, D.,Jones, J. P.,et.al. Exercise-Induced Transcription of the Muscle Glucose Transporter (Glut 4) Gene[J].Biochemical and biophysical research communications,2002,292(2): 409-414.
[28]Gao, X.,Jin, C.,Xue, Y.,et.al. Computational Analyses of Tbc Protein Family in Eukaryotes[J].Protein and peptide letters,2008,15(5):505-509.
[29]Stone, S.,Abkevich, V.,Russell, D. L.,et.al. Tbcldl Is a Candidate for a Severe Obesity Gene and Evidence for a Gene/Gene Interaction in Obesity Predisposition[J].Human molecular genetics,2006, 15(18):2709.
[30]White, R. A.,Pasztor, L. M.,Richardson, P. M.,et.al. The Gene Encoding Tbcldl with Homology to the Tre-2/Usp6 Oncogene, Bub2, and Cdc16 Maps to Mouse Chromosome 5 and Human Chromosome 4[J].Cytogenetic and Genome Research,2000,89(3-4):272-275.
[31]Sakamoto, K.,Holman, G. D. Emerging Role for As160/Tbcld4 and Tbcldl in the Regulation of Glut4 Traffic[J].American Journal of Physiology-Endocrinology And Metabolism,2008,295(1): E29.
[32]Funai, K. Effects of in Vivo Exercise and in Vitro Contractile Activity on the Regulation of As160, Tbcldl and Glucose Transport in Rat Skeletal Muscle. The University of Michigan.2010
[33]E, A.,Zielak,Forde, N.,et.al. Identification of Novel Genes Associated with Dominant Follicle Development in Cattle[J].Vertebrate Reproductive Science & Technology 2007,19(8):967-975.
[34]Zhou, Q. L.,Jiang, Z. Y.,Holik, J.,et.al. Akt Substrate Tbcldl Regulates Glutl Expression through the Mtor Pathway in 3t3-L1 Adipocytes[J].The Biochemical journal,2008,411(3):647.
[35]Chadt, A.,Leicht, K.,Deshmukh, A.,et.al. Tbcldl Mutation in Lean Mouse Strain Confers Leanness and Protects from Diet-Induced Obesity[J].Nature genetics,2008,40(11):1354-1359.
[36]Koumanov, F.,Holman, G. D. Thrifty Tbcldl and Tbcld4 Proteins Link Signalling and Membrane Trafficking Pathways[J].Biochemical Journal,2007,403(Pt 2).
[37]Li, Shuai.,Francisco, A. B.,Han, C.,et.al. The Full-Length Isoform of the Mouse Pleckstrin Homology Domain-Interacting Protein (Phip) Is Required for Postnatal Growth[J].FEBS letters.
[38]Nosaka, T.,Kawashima, T.,Misawa, K.,et.al.'Stat5 as a Molecular Regulator of Proliferation, Differentiation and Apoptosis in Hematopoietic Cells[J].The EMBO journal,1999,18(17): 4754-4765.
[39]Onishi, M.,Nosaka, T.,Misawa, K.,et.al. Identification and Characterization of a Constitutively Active Stat5 Mutant That Promotes Cell Proliferation[J].Molecular and cellular biology,1998,18(7): 3871.
[40]Nogueira, V.,Park, Y.,Chen, C. C.,et.al. Akt Determines Replicative Senescence and Oxidative or Oncogenic Premature Senescence and Sensitizes Cells to Oxidative Apoptosis[J].Cancer Cell,2008, 14(6):458-470.
[41]Weber, I. T.,Fang, B.,Agniswamy, J. Caspases:Structure-Guided Design of Drugs to Control Cell Death[J].Mini Reviews in Medicinal Chemistry,2008,8(11):1154-1162.
[42]Fang, B.,Boross, P. I.,Tozser, J.,et.al. Structural and Kinetic Analysis of Caspase-3 Reveals Role for S5 Binding Site in Substrate Recognition[J].Journal of molecular biology,2006,360(3):654-666.
[43]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]. Journal of Clinical Investigation,1999, 103:253-260.
[44]KJ, L. Analysis of Relative Gene Expression Data Using Real-Time Quantitative Pcr and the 2(-Delta Delta C(T)) Method. [M].2001:402-408.
[45]Zeng, L.,Zhou, M. M. Bromodomain:An Acetyl-Lysine Binding Domain[J].FEBS letters,2002, 513(1):124-128.
[46]Davuluri, R. V.,Suzuki, Y.,Sugano, S.,et.al. The Functional Consequences of Alternative Promoter Use in Mammalian Genomes. [J].Trends in Genetics,2008,24:167-177.
[47]Aguirre, V.,Uchida, T.,Yenush, L.,et.al. The C-Jun Nh2-Terminal Kinase Promotes Insulin Resistance During Association with Insulin Receptor Substrate-1 and Phosphorylation of Ser307[J].Journal of Biological Chemistry,2000,275(12):9047.
[48]ChunChun, H.,JiWen, W.,LiAng, L.,et.al. The Role of Insulin and Glucose in Goose Primary Hepatocyte Triglyceride Accumulation[J].Journal of Experimental Biology,2009,212(10): 1553-1558.
[49]Bosco, D.,Costa, R.,Plastino, M.,et.al. Glucose Metabolism in the Idiopathic Blepharoptosis:Utility of the Oral Glucose Tolerance Test (Ogtt) and of the Insulin Resistance Index[J].Journal of the neurological sciences,2009,284(1-2):24-28.
[50]Valverde, A. M.,Kahn, C.,Beinborn, M. Insulin Signaling in Insulin Receptor Substrate(Irs)-1-Deficient Brown Adipocytes[J].Diabetes,1999,48(11):2122-2131.
[51]Carvalho, E.,Rondinone, C.,Smith, U. Insulin Resistance in Fat Cells from Obese Zucker Rats-Evidence for an Impaired Activation and Translocation of Protein Kinase B and Glucose Transporter 4.[J].Mol cell biochem,2000,206:7-16.
[52]Ide, T.,Shimano, H.,Yahagi, N.,et.al. Srebps Suppress Irs-2-Mediated Insulin Signalling in the Liver.[J]. Nat Cell Biol,2004,4(351-357).
[53]郝军,刘青娟,郑书深,等.不同浓度胰岛素对人肾小管上皮细胞SREBP-1, FAS表达及脂质形成的影响[J].中国病理生理杂志,26(007)：1275-1279.
[54]Halaas, J. L.,Gajiwala, K. S.,Maffei, M.,et.al. Weight-Reducing Effects of the Plasma Protein Encoded by the Obese Gene[J].Science,1995,269(5223):543.
[55]Yahagi, N.,Shimano, H.,Hasty, A. H.,et.al. Absence of Sterol Regulatory Element-Binding Protein-1 (Srebp-1) Ameliorates Fatty Livers but Not Obesity or Insulin Resistance Inlep Ob/Lep Ob Mice[J].Journal of Biological Chemistry,2002,277(22):19353.
[56]Horton, J. D.,Shah, N. A.,Warrington, J. A.,et.al. Combined Analysis of Oligonucleotide Microarray Data from Transgenic and Knockout Mice Identifies Direct Srebp Target Genes[J].Proceedings of the National Academy of Sciences of the United States of America,2003,100(21):12027.
[57]Shimomura, I.,Hammer, R. E.,Richardson, J. A.,et.al. Insulin Resistance and Diabetes Mellitus in Transgenic Mice Expressing Nuclear Srebp-lc in Adipose Tissue:Model for Congenital Generalized Lipodystrophy[J].Genes & development,1998,12(20):3182.
[58]向梳瑕.葡萄糖和胰岛素对鹅肝细胞内葡萄糖代谢平衡的研究[J].学位论文,雅安,四川农业大学,2010.
[59]Matsusue, K.,Kusakabe, T.,Noguchi, T., et.al. Hepatic Steatosis in Leptin-Deficient Mice Is Promoted by the Ppar [Gamma] Target Gene Fsp27[J].Cell Metabolism,2008,7(4):302-311.
[60]Dugan, M. E. R.,Aalhus, J. L.,Schaefer, A. L., et.al. The Effect of Conjugated Linoleic Acid on Fat to Lean Repartitioning and Feed Conversion in Pigs[J].Canadian journal of animal science,1997, 77(4):723-725.
[61]郝军,刘淑霞,刘青娟,等.胰岛素对人肾小管上皮细胞SREBP-1, FAS表达及脂质代谢的时效性研究[J].巾国药理学通报,2010,26(004)：517-521.
[62]韩春春,王继文,符自英,等.葡萄糖和胰岛素对鹅肝细胞脂肪酸合成酶活性及转录表达的影响[J].农业生物技术学报,2009,(004)：634-637.
[63]李翔,周圻,王玉莲,等.鹅肥肝形成机理的研究[J].动物科学与动物医学,2004,21(010)：32-34.
[64]Mourot, J.,Guy, G.,Lagarrigue, S., et.al. Role of Hepatic Lipogenesis in the Susceptibility to Fatty Liver in the Goose (Anser Anser)[J].Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology,2000,126(1):81-87.
[65]Yu ZW,Eriksson JW.The upregulating effect of insulin and vanadate on cell surface insulin receptors in rat adipocytes is modulated by glucose and energy availability.Horm Metab Res,2000,32:310-315.
[66]Pillay TS,Xiao S,Olefshy JM.Glucose-induced phosphorylation of the insulin receptor[J].J Clin Invest,1996,97:613-620.
[67]刘慧霞,李莉蓉.高糖对大鼠脂肪细胞胰岛素信号蛋白磷酸化的影响[J].中华内分泌代谢杂志,2002,18(005)：391-394.
[68]韩春春.不同因素诱导鹅肝细胞脂肪变性的机理研究[J].学位论文,雅安,四川农业大学,2010.
[69]Denechaud, P. D.,Bossard, P.,Lobaccaro, J. M. A., et.al. Chrebp, but Not Lxrs, Is Required for the Induction of Glucose-Regulated Genes in Mouse Liver[J].The Journal of clinical investigation,2008, 118(3):956.
[70]Sakiyama, H.,Wynn, R. M.,Lee, W. R., et.al. Regulation of Nuclear Import/Export of Carbohydrate Response Element-Binding Protein (Chrebp):Interaction of an A-Helix of Chrebp with the 14-3-3 Proteins and Regulation by Phosphorylation[J].The Journal of biological chemistry,2008,283(36): 24899-24908.
[71]Uyeda, K.,Yamashita, H.,Kawaguchi, T. Carbohydrate Responsive Element-Binding Protein (Chrebp):A Key Regulator of Glucose Metabolism and Fat Storage[J].Biochemical pharmacology, 2002,63(12):2075-2080.
[72]Mitro, N.,Mak, P. A.,Vargas, L., et.al. The Nuclear Receptor Lxr Is a Glucose Sensor[J].Nature, 2006,445(7124):219-223.
[73]Danilova, O. V.,Tai, A. K.,Mele, D. A., et.al. Neurogenin 3-Specific Dipeptidyl Peptidase-2 Deficiency Causes Impaired Glucose Tolerance, Insulin Resistance, and Visceral Obesity[J].Endocrinology,2009,150(12):5240.
[74]Haus, J. M.,Solomon, T. P. J.,Marchetti, C. M., et.al. Free Fatty Acid-Induced Hepatic Insulin Resistance Is Attenuated Following Lifestyle Intervention in Obese Individuals with Impaired Glucose Tolerance[J]. Journal of Clinical Endocrinology & Metabolism,2010,95(1):323.
[75]Foufelle, F.,Ferre, P. New Perspectives in the Regulation of Hepatic Glycolytic and Lipogenic Genes by Insulin and Glucose:A Role for the Transcription Factor Sterol Regulatory Element Binding Protein-1c[J].Biochemical Journal,2002,366-377.
[76]Koo, S. H.,Dutcher, A. K.,Towle, H. C. Glucose and Insulin Function through Two Distinct Transcription Factors to Stimulate Expression of Lipogenic Enzyme Genes in Liver[J].Journal of Biological Chemistry,2001,276(12):9437.
[77]Li, M.,Youngren, J. F.,Dunaif, A.,et.al. Decreased Insulin Receptor (Ir) Autophosphorylation in Fibroblasts from Patients with Pcos:Effects of Serine Kinase Inhibitors and Ir Activators[J].Journal of Clinical Endocrinology & Metabolism,2002,87(9):4088.
[78]Tirosh, A.,Potashnik, R.,Bashan, N., et.al. Oxidative Stress Disrupts Insulin-Induced Cellular Redistribution of Insulin Receptor Substrate-1 and Phosphatidylinositol 3-Kinase in 3t3-L1 Adipocytes. A Putative Cellular Mechanism for Impaired Protein Kinase B Activation and Glut4 Translocation[J].The Journal of biological chemistry,1999,274(15):10595.
[79]刘慧霞,何碧秀,陈碧莲,等.高胰岛素和高糖对大鼠脂肪细胞胰岛素信号蛋白的影响[J].中国糖尿病杂志,2003,11(002)：118-121.
[80]Tanti, J. F.,Gremeaux, T.,Grillo, S., et.al. Overexpression of a Constitutively Active Form of Phosphatidylinositol 3-Kinase Is Sufficient to Promote Glut 4 Translocation in Adipocytes[J].Journal of Biological Chemistry,1996,271(41):25227.
[81]Pillay, T. S.,Xiao, S.,Olefsky, J. M. Glucose-Induced Phosphorylation of the Insulin Receptor. Functional Effects and Characterization of Phosphorylation Sites[J].Journal of Clinical Investigation, 1996,97(3):613.
[82]Jian-Xiong, L.,Fen-Fen, C.,Gong-She, Y. Effect of Insulin on Transcription of Lipogenic and Lipolytic-Related Genes and Lipid Metabolism in Primary Porcine Adipocytes[J].Chinese Journal of Agricultural Biotechnology,2006,3(02):135-140.
[83]Foufelle, F.,Lepetit, N.,Bosc, D., et.al. Dnase I Hypersensitivity Sites and Nuclear Protein Binding on the Fatty Acid Synthase Gene:Identification of an Element with Properties Similar to Known Glucose-Responsive Elements[J].Biochemical Journal,1995,308(Pt 2):521.
[84]Choi, S. S.,Diehl, A. M. Hepatic Triglyceride Synthesis and Nonalcoholic Fatty Liver Disease[J].Current opinion in lipidology,2008,19(3):295.
[85]Decaux, J. F.,Marcillat, O.,Pichard, A. L., et.al. Glucose-Dependent and-Independent Effect of Insulin on Gene Expression[J].Journal of Biological Chemistry,1991,266(6):3432.