共查询到20条相似文献，搜索用时 15 毫秒
1.
Yuan M Konstantopoulos N Lee J Hansen L Li ZW Karin M Shoelson SE 《Science (New York, N.Y.)》2001,293(5535):1673-1677
We show that high doses of salicylates reverse hyperglycemia, hyperinsulinemia, and dyslipidemia in obese rodents by sensitizing insulin signaling. Activation or overexpression of the IkappaB kinase beta (IKKbeta) attenuated insulin signaling in cultured cells, whereas IKKbeta inhibition reversed insulin resistance. Thus, IKKbeta, rather than the cyclooxygenases, appears to be the relevant molecular target. Heterozygous deletion (Ikkbeta+/-) protected against the development of insulin resistance during high-fat feeding and in obese Lep(ob/ob) mice. These findings implicate an inflammatory process in the pathogenesis of insulin resistance in obesity and type 2 diabetes mellitus and identify the IKKbeta pathway as a target for insulin sensitization. 相似文献
2.
Hussain K Challis B Rocha N Payne F Minic M Thompson A Daly A Scott C Harris J Smillie BJ Savage DB Ramaswami U De Lonlay P O'Rahilly S Barroso I Semple RK 《Science (New York, N.Y.)》2011,334(6055):474
Pathological fasting hypoglycemia in humans is usually explained by excessive circulating insulin or insulin-like molecules or by inborn errors of metabolism impairing liver glucose production. We studied three unrelated children with unexplained, recurrent, and severe fasting hypoglycemia and asymmetrical growth. All were found to carry the same de novo mutation, p.Glu17Lys, in the serine/threonine kinase AKT2, in two cases as heterozygotes and in one case in mosaic form. In heterologous cells, the mutant AKT2 was constitutively recruited to the plasma membrane, leading to insulin-independent activation of downstream signaling. Thus, systemic metabolic disease can result from constitutive, cell-autonomous activation of signaling pathways normally controlled by insulin. 相似文献
3.
Ozcan U Cao Q Yilmaz E Lee AH Iwakoshi NN Ozdelen E Tuncman G Görgün C Glimcher LH Hotamisligil GS 《Science (New York, N.Y.)》2004,306(5695):457-461
4.
Insulin resistance is a major hallmark in the development of type II diabetes, which is characterized by the failure of insulin to promote glucose uptake in muscle and to suppress glucose production in liver. The serine-threonine kinase Akt (PKB) is a principal target of insulin signaling that inhibits hepatic glucose output when glucose is available from food. Here we show that TRB3, a mammalian homolog of Drosophila tribbles, functions as a negative modulator of Akt. TRB3 expression is induced in liver under fasting conditions, and TRB3 disrupts insulin signaling by binding directly to Akt and blocking activation of the kinase. Amounts of TRB3 RNA and protein were increased in livers of db/db diabetic mice compared with those in wild-type mice. Hepatic overexpression of TRB3 in amounts comparable to those in db/db mice promoted hyperglycemia and glucose intolerance. Our results suggest that, by interfering with Akt activation, TRB3 contributes to insulin resistance in individuals with susceptibility to type II diabetes. 相似文献
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6.
【目的】克隆内蒙古白绒山羊AKT基因cDNA并分析其基本表达模式。【方法】RT-PCR克隆AKT基因 cDNA。通过在线软件BLAST进行核酸序列分析,用SMART与Psite进行氨基酸序列分析。半定量RT-PCR检测AKT基因在绒山羊组织中的表达特异性。Western blotting检测绒山羊胎儿成纤维细胞中AKT表达。【结果】克隆到的内蒙古白绒山羊AKT基因cDNA片段长 1 443 bp,包含了编码480个氨基酸残基的全长ORF,氨基酸序列与绵羊（NM_001161857.1）同源性为97%。SMART分析表明,ORF编码的蛋白包含了可与3-磷酸肌醇结合的PH结构域及具有丝氨酸/苏氨酸激酶催化活性的S_TKc结构域。Psite分析表明,含有1个cAMP-/cGMP-依赖性蛋白激酶磷酸化位点、6个蛋白激酶C磷酸化位点、10个酪蛋白激酶Ⅱ磷酸化位点、2个蛋白激酶ATP结合区信号和1个丝氨酸/苏氨酸蛋白激酶活性区域。PSORT程序预测其定位于细胞质中。AKT基因mRNA丰度在睾丸、脑和肾中较高,在脾、肝、肺及乳腺组织中相对低。绒山羊胎儿成纤维细胞中抑制mTOR活性,AKT表达量降低。【结论】内蒙古白绒山羊AKT基因cDNA全长ORF的核苷酸序列与绵羊的AKT基因具有很高的同源性,AKT基因在脾、睾丸、脑、肝、肺、乳腺及肾组织中均有表达,其AKT的表达受mTOR信号通路的调控。 相似文献
7.
Two mutant alleles of the insulin receptor gene in a patient with extreme insulin resistance 总被引：26，自引：0，他引：26
T Kadowaki C L Bevins A Cama K Ojamaa B Marcus-Samuels H Kadowaki L Beitz C McKeon S I Taylor 《Science (New York, N.Y.)》1988,240(4853):787-790
Insulin receptor complementary DNA has been cloned from an insulin-resistant patient with leprechaunism whose receptors exhibited multiple abnormalities in insulin binding. The patient is a compound heterozygote, having inherited two different mutant alleles of the insulin receptor gene. One allele contains a missense mutation encoding the substitution of glutamic acid for lysine at position 460 in the alpha subunit of the receptor. The second allele has a nonsense mutation causing premature chain termination after amino acid 671 in the alpha subunit, thereby deleting both the transmembrane and tyrosine kinase domains of the receptor. Interestingly, the father is heterozygous for this nonsense mutation and exhibits a moderate degree of insulin resistance. This raises the possibility that mutations in the insulin receptor gene may account for the insulin resistance in some patients with non-insulin-dependent diabetes mellitus. 相似文献
8.
细胞自噬是哺乳动物细胞物质代谢的一个重要机制,与细胞凋亡共同参与卵巢卵泡的发育和闭锁,并发挥重要的作用。近年研究发现,磷脂酰肌醇3-激酶/蛋白激酶B（phosphatidylinositol 3-kinase/protein kinase B,PI3K/AKT）信号通路参与卵巢疾病的发生。PI3K和AKT的过度激活可使原始卵泡过早发育以及卵泡过快凋亡,卵巢颗粒细胞作为卵泡发育重要的支持细胞,其功能的减退或凋亡很可能引发一系列女性内分泌方面的疾病。FOXO3a转录因子是PI3K/AKT信号通路下游的重要靶蛋白之一,参与抗增殖和凋亡。本文就关于卵巢颗粒细胞自噬与PI3K/AKT/FOXO3a信号通路的相关进展加以综述。 相似文献
9.
Fish oil prevents insulin resistance induced by high-fat feeding in rats 总被引：21，自引：0，他引：21
L H Storlien E W Kraegen D J Chisholm G L Ford D G Bruce W S Pascoe 《Science (New York, N.Y.)》1987,237(4817):885-888
Non-insulin-dependent diabetes mellitus is an increasingly prevalent disease in Western and developing societies. A major metabolic abnormality of non-insulin-dependent diabetes is impaired insulin action (insulin resistance). Diets high in fat from vegetable and nonaquatic animal sources (rich in linoleic acid, an omega-6 fatty acid, and saturated fats) lead to insulin resistance. In rats fed high-fat diets, replacement of only 6 percent of the linoleic omega-6 fatty acids from safflower oil with long-chain polyunsaturated omega-3 fatty acids from fish oil prevented the development of insulin resistance. The effect was most pronounced in the liver and skeletal muscle, which have important roles in glucose supply and demand. The results may be important for therapy or prevention of non-insulin-dependent diabetes mellitus. 相似文献
10.
随着经济发展、人们生活方式改变,糖尿病已严重威胁人类健康。胰岛素抵抗是2型糖尿病发生的关键因素,从胰岛素合成后与胰岛素受体结合到实现生理效应的一系列过程中,都可能发生异常。运动疗法能够提高组织对胰岛素的敏感性,提高机体维持血糖稳定的激素调节能力。查阅了近年来国内外有关运动干预骨骼肌胰岛素功能的研究情况,分析了运动对骨骼肌胰岛素影响的主要因素,以及不同运动形式对骨骼肌胰岛素的影响。 相似文献
11.
White MF 《Science (New York, N.Y.)》2003,302(5651):1710-1711
The signaling pathways used by insulin have been identified [M. White, Insulin Signaling Pathway, Sci. STKE (Connections Map, as seen November 2003), http://stke.sciencemag.org/cgi/cm/cmp_12069]. Now our challenge is to understand how the failure of these signals is associated with obesity and the progressive failure of pancreatic beta cells that leads to diabetes. Whether better management of chronic inflammation can improve insulin action is an important area of investigation. Drugs that stimulate IRS2 (insulin receptor substrate protein 2) synthesis or signaling might be a good starting point. This knowledge will lead to rational strategies that prevent or cure diabetes. 相似文献
12.
Human diabetes associated with a deletion of the tyrosine kinase domain of the insulin receptor 总被引：11，自引：0，他引：11
M Taira M Taira N Hashimoto F Shimada Y Suzuki A Kanatsuka F Nakamura Y Ebina M Tatibana H Makino 《Science (New York, N.Y.)》1989,245(4913):63-66
The insulin receptor has an intrinsic tyrosine kinase activity that is essential for signal transduction. A mutant insulin receptor gene lacking almost the entire kinase domain has been identified in an individual with type A insulin resistance and acanthosis nigricans. Insulin binding to the erythrocytes or cultured fibroblasts from this individual was normal. However receptor autophosphorylation and tyrosine kinase activity toward an exogenous substrate were reduced in partially purified insulin receptors from the proband's lymphocytes that had been transformed by Epstein-Barr virus. The insulin resistance associated with this mutated gene was inherited by the proband from her mother as an apparently autosomal dominant trait. Thus a deletion in one allele of the insulin receptor gene may be at least partly responsible for some instances of insulin-resistant diabetes. 相似文献
13.
表没食子儿茶素没食子酸酯(Epigallocatechin gallate,EGCG)是绿茶中的主要活性成分,具有抗癌、抑制肥胖、缓解代谢综合征等功效。本文总结EGCG预防和缓解糖尿病的相关研究,从降血糖功效、胰岛素抵抗、胰岛素分泌、糖尿病常见并发症等方面综合分析和阐述EGCG的作用机制,以期为绿茶缓解代谢综合征研究提供理论支持。 相似文献
14.
Milan D Jeon JT Looft C Amarger V Robic A Thelander M Rogel-Gaillard C Paul S Iannuccelli N Rask L Ronne H Lundström K Reinsch N Gellin J Kalm E Roy PL Chardon P Andersson L 《Science (New York, N.Y.)》2000,288(5469):1248-1251
A high proportion of purebred Hampshire pigs carries the dominant RN- mutation, which causes high glycogen content in skeletal muscle. The mutation has beneficial effects on meat content but detrimental effects on processing yield. Here, it is shown that the mutation is a nonconservative substitution (R200Q) in the PRKAG3 gene, which encodes a muscle-specific isoform of the regulatory gamma subunit of adenosine monophosphate-activated protein kinase (AMPK). Loss-of-function mutations in the homologous gene in yeast (SNF4) cause defects in glucose metabolism, including glycogen storage. Further analysis of the PRKAG3 signaling pathway may provide insights into muscle physiology as well as the pathogenesis of noninsulin-dependent diabetes mellitus in humans, a metabolic disorder associated with impaired glycogen synthesis. 相似文献
15.
赵云鹏 《上海交通大学学报(农业科学版)》2016,(4):106-108
探讨中等强度有氧运动对2型糖尿病患者胰岛素抵抗相关因素的影响。选取海南医学院附属医院内分泌科自2011年2月至2014年3月确诊的2型糖尿病（T2DM）患者86例,随机分成两组。观察组46例,其中男25例,女21例;对照组40例,其中男23例,女17例。对照组继续按照糖尿病的一般治疗进行教育与自我检测血糖,同时按照医院治疗方案进行口服药物或胰岛素注射等基础治疗。观察组除上述治疗外,按照美国糖尿病学会（ADA）与美国运动医学学会（ACSM）于2010年颁布的《2型糖尿病运动指南》中的推荐,制定针对个体的不同中等强度运动方案。两组患者在实验前及12个月后晨起空腹状态测定BMI、体脂率、FPG、HbA1c、FINS、HOMA-IR。研究显示长期中等强度有氧运动对2型糖尿病患者BMI、体脂率、FPG、HbA1c、FINS、HOMA-IR等指标有显著影响。 相似文献
16.
Servant G Weiner OD Herzmark P Balla T Sedat JW Bourne HR 《Science (New York, N.Y.)》2000,287(5455):1037-1040
Morphologic polarity is necessary for chemotaxis of mammalian cells. As a probe of intracellular signals responsible for this asymmetry, the pleckstrin homology domain of the AKT protein kinase (or protein kinase B), tagged with the green fluorescent protein (PHAKT-GFP), was expressed in neutrophils. Upon exposure of cells to chemoattractant, PHAKT-GFP is recruited selectively to membrane at the cell's leading edge, indicating an internal signaling gradient that is much steeper than that of the chemoattractant. Translocation of PHAKT-GFP is inhibited by toxin-B from Clostridium difficile, indicating that it requires activity of one or more Rho guanosine triphosphatases. 相似文献
17.
钙调神经磷酸酶B样相互作用蛋白激酶(CIPK)蛋白家族是由Ca2+介导的植物信号通路中的关键蛋白家族,在植物抗逆和生长发育中起关键作用。本研究将生物信息学方法和转录组数据分析相结合,挖掘出大麦31个HvCIPK基因家族成员并将其分为5个亚家族。HvCIPKs基因家族成员具有CIPKs典型的N端激酶结构域和C端NAF调节结构域;蛋白质分子量在40302.27~89926.43KDa之间,为亲水性蛋白;启动子总共包含11种与非生物胁迫、激素调控以及生长发育相关的顺式作用元件;蛋白互作网络预测结果显示,HvCIPKs与Na+、K+转运体、ABA信号通路关键蛋白(SOS1、AKT1和ABL2)存在相互作用关系;转录组数据分析发现HvCIPK1、HvCIPK2、HvCIPK6、HvCIPK9、HvCIPK11受盐碱胁迫的诱导表达。该研究为进一步探索大麦HvCIPKs基因家族功能及调控机制提供理论依据。 相似文献
18.
目的:了解2型糖尿病合并高血压患者血清脂联素和内脏脂肪素的变化,探讨脂联素和内脏脂肪素与2型糖尿病合并高血压的相关性.方法:选取高血压患者40例,2型糖尿病患者38例,2型糖尿病合并高血压患者40例,健康对照者40例作为研究对象,测定其血清脂联素和内脏脂肪素水平,同时测定血压、血糖、血脂和体质量指数等指标,并分析以上指标与脂联素和内脏脂肪素的关系.结果:单纯2型糖尿病组和单纯高血压组内脏脂肪素水平明显高于正常对照组,分别为(18.26±1.22)ng/mL,(17.31±1.26)ng/mL和(13.32±1.31)ng/mL(p<0.05);2型糖尿病合并高血压组(24.99±1.36)ng/mL又明显高于单纯2型糖尿病组和单纯高血压组.2型糖尿病组和高血压组脂联素水平明显低于正常对照组,分别为(8.75±1.29)μg/mL,(9.71±1.28)μg/mL和(12.67±1.48)μg/mL(p<0.05);2型糖尿病合并高血压组(5.73±1.23)μg/mL又明显低于单纯2型糖尿病组和单纯高血压组.2型糖尿病组和高血压组的脂联素和内脏脂肪素水平差异不具有统计学意义(p>0.05).相关分析显示2型糖... 相似文献
19.
Diabetes, a new mutation in the mouse 总被引：25，自引：0，他引：25
Diabetes (db), which occurred in an inbred strain of mouse, is inherited as a unit autosomal recessive and is characterized by a metabolic disturbance resembling diabetes mellitus in man. Abnormal deposition of fat at 3 to 4 weeks of age is followed shortly by hyperglycemia, polyuria, and glycosuria. Accompanying morphological changes in the islets of Langerhans suggest neogenesis to compensate for insulin depletion. 相似文献