共查询到20条相似文献,搜索用时 15 毫秒
1.
Insulin-resistant diabetes due to a point mutation that prevents insulin proreceptor processing 总被引:21,自引:0,他引:21
Y Yoshimasa S Seino J Whittaker T Kakehi A Kosaki H Kuzuya H Imura G I Bell D F Steiner 《Science (New York, N.Y.)》1988,240(4853):784-787
A point mutation in the human insulin receptor gene in a patient with type A insulin resistance alters the amino acid sequence within the tetrabasic processing site of the proreceptor molecule from Arg-Lys-Arg-Arg to Arg-Lys-Arg-Ser. Epstein-Barr virus-transformed lymphocytes from this patient synthesize an insulin receptor precursor that is normally glycosylated and inserted into the plasma membrane but is not cleaved to mature alpha and beta subunits. Insulin binding to these cells is severely reduced but can be increased about fivefold by gentle treatment with trypsin, accompanied by the appearance of normal alpha subunits. These results indicate that proteolysis of the proreceptor is necessary for its normal full insulin-binding sensitivity and signal-transducing activity and that a cellular protease that is more stringent in its specificity than trypsin is required to process the receptor precursor. 相似文献
2.
2型糖尿病患者微血管病变与血液流变学变化、胰岛素抵抗的相关性 总被引:5,自引:0,他引:5
目的 :研究血液流变学变化和胰岛素抵抗与 2型糖尿病微血管病变的关系。方法 :检测 10 6例 2型糖尿病患者 ,其中有微血管并发症 5 3例 ,无微血管并发症 5 3例 ,以及 5 3例正常对照组的血液流变学、空腹血糖、空腹胰岛素 ,计算胰岛素敏感性指数 (ISI) ,并进行比较。结果 :糖尿病两组全血粘度和血浆粘度均显著高于正常对照组 ;ISI则显著低于正常对照组 (P<0 .0 1)。糖尿病有微血管病变组全血粘度和血浆粘度显著高于无微血管病变组 ;ISI显著低于无微血管病变组 (P<0 .0 1)。多元逐步回归分析显示 ,2型糖尿病微血管病变与糖尿病病程、血糖、全血粘度和血浆粘度呈显著正相关 (r=0 .62 4,0 .42 8,0 .3 46,0 .3 82 ,P值分别 <0 .0 0 1,0 .0 1,0 .0 5 ,0 .0 1) ,与 ISI呈显著负相关 (r=-0 .3 5 2 ,P<0 .0 5 )。结论 :2型糖尿病微血管病变患者存在持续性的高血糖、高血液粘度 ,糖尿病病程的延长 ,严重的胰岛素抵抗为 2型糖尿病微血管病变的主要危险因素。 相似文献
3.
Human diabetes associated with a mutation in the tyrosine kinase domain of the insulin receptor 总被引:12,自引:0,他引:12
M Odawara T Kadowaki R Yamamoto Y Shibasaki K Tobe D Accili C Bevins Y Mikami N Matsuura Y Akanuma 《Science (New York, N.Y.)》1989,245(4913):66-68
Insulin receptor complementary DNA has been cloned from an insulin-resistant individual whose receptors have impaired tyrosine protein kinase activity. One of this individual's alleles has a mutation in which valine is substituted for Gly996, the third glycine in the conserved Gly-X-Gly-X-X-Gly motif in the putative binding site fo adenosine triphosphate. Expression of the mutant receptor by transfection into Chinese hamster ovary cells confirmed that the mutation impairs tyrosine kinase activity. 相似文献
4.
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
5.
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
6.
Mani A Radhakrishnan J Wang H Mani A Mani MA Nelson-Williams C Carew KS Mane S Najmabadi H Wu D Lifton RP 《Science (New York, N.Y.)》2007,315(5816):1278-1282
Coronary artery disease (CAD) is the leading cause of death worldwide and is commonly caused by a constellation of risk factors called the metabolic syndrome. We characterized a family with autosomal dominant early CAD, features of the metabolic syndrome (hyperlipidemia, hypertension, and diabetes), and osteoporosis. These traits showed genetic linkage to a short segment of chromosome 12p, in which we identified a missense mutation in LRP6, which encodes a co-receptor in the Wnt signaling pathway. The mutation, which substitutes cysteine for arginine at a highly conserved residue of an epidermal growth factor-like domain, impairs Wnt signaling in vitro. These results link a single gene defect in Wnt signaling to CAD and multiple cardiovascular risk factors. 相似文献
7.
目的比较持续皮下胰岛素输注(CSII)和多次胰岛素皮下注射(MSII)在2型糖尿病强化降糖中的效果。方法将48例2型糖尿病患者随机分成CSII组(n=26)和MSII组(n=22)两组,CSII组的患者采用胰岛素泵降糖治疗,MSII组的患者采用胰岛素笔降糖治疗。监测两组患者治疗前后全天血糖谱的变化,观察并比较血糖达标所需要的时间、胰岛素用量、低血糖发生率等情况。结果CSII组与MSII组相比,血糖达标所需的时间、胰岛素用量及低血糖发生率等差异有显著统计学意义(P<0.01)。结论持续皮下胰岛素输注和多次胰岛素皮下注射对2型糖尿病患者强化降糖治疗均有效,但胰岛素泵降糖效果优于胰岛素笔。 相似文献
8.
水稻空间诱变育种抗稻瘟病研究进展 总被引:5,自引:0,他引:5
空间诱变育种抗病性研究正越来越受到重视,我国利用空间诱变育种技术,已选育出一些抗稻瘟病新品种和新抗源.文章对水稻空间诱变稻瘟病抗性变异特点及空间诱变抗稻瘟病育种成果,以及空间诱变稻瘟病抗性变异机理的研究进展进行了综述,并对水稻空间诱变育种抗稻瘟病的研究前景进行了展望. 相似文献
9.
Polymorphism in the 5'-flanking region of the human insulin gene and its possible relation to type 2 diabetes 总被引:11,自引:0,他引:11
P Rotwein R Chyn J Chirgwin B Cordell H M Goodman M A Permut 《Science (New York, N.Y.)》1981,213(4512):1117-1120
10.
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
11.
Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity 总被引:2,自引:0,他引:2
Lamming DW Ye L Katajisto P Goncalves MD Saitoh M Stevens DM Davis JG Salmon AB Richardson A Ahima RS Guertin DA Sabatini DM Baur JA 《Science (New York, N.Y.)》2012,335(6076):1638-1643
Rapamycin, an inhibitor of mechanistic target of rapamycin complex 1 (mTORC1), extends the life spans of yeast, flies, and mice. Calorie restriction, which increases life span and insulin sensitivity, is proposed to function by inhibition of mTORC1, yet paradoxically, chronic administration of rapamycin substantially impairs glucose tolerance and insulin action. We demonstrate that rapamycin disrupted a second mTOR complex, mTORC2, in vivo and that mTORC2 was required for the insulin-mediated suppression of hepatic gluconeogenesis. Further, decreased mTORC1 signaling was sufficient to extend life span independently from changes in glucose homeostasis, as female mice heterozygous for both mTOR and mLST8 exhibited decreased mTORC1 activity and extended life span but had normal glucose tolerance and insulin sensitivity. Thus, mTORC2 disruption is an important mediator of the effects of rapamycin in vivo. 相似文献
12.
Cho H Mu J Kim JK Thorvaldsen JL Chu Q Crenshaw EB Kaestner KH Bartolomei MS Shulman GI Birnbaum MJ 《Science (New York, N.Y.)》2001,292(5522):1728-1731
Glucose homeostasis depends on insulin responsiveness in target tissues, most importantly, muscle and liver. The critical initial steps in insulin action include phosphorylation of scaffolding proteins and activation of phosphatidylinositol 3-kinase. These early events lead to activation of the serine-threonine protein kinase Akt, also known as protein kinase B. We show that mice deficient in Akt2 are impaired in the ability of insulin to lower blood glucose because of defects in the action of the hormone on liver and skeletal muscle. These data establish Akt2 as an essential gene in the maintenance of normal glucose homeostasis. 相似文献
13.
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
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《山西农业大学学报(自然科学版)》2020,(1)
[目的]蛋白激酶是一类催化蛋白质磷酸化反应的酶,普遍存在于植物体中,参与调控植物生长发育和抗逆等多种生理反应。本文旨在探究谷子响应干旱胁迫与蛋白激酶之间的关系,为谷子抗旱品种的培育提供参考。[方法]运用生物信息学方法,分析了谷子蛋白激酶基因家族的35个抗旱相关蛋白激酶基因的系统进化关系、基因结构、保守基序、保守结构域、启动子顺式元件以及在干旱处理下和不同组织中基因表达水平。[结果]这35个谷子抗旱相关蛋白激酶基因分布于8条染色体上,被分为4个亚家族;多数亲缘关系较近的基因,其外显子-内含子结构、保守基序、保守结构域也较为相似,它们可能具有功能上的相似性;启动子元件分析发现,多数基因启动子区含有ABA响应元件(ABRE)和干旱诱导响应元件(MBS);组织特异性表达发现,SiPK20和SiPK25基因表现出显著的组织特异性表达模式,SiPK20在叶中表达量较高,SiPK25在根中表达量较高;干旱诱导基因表达分析显示,在抗旱品种勾勾母鸡咀中,干旱处理后SiPK1和SiPK4基因表达量显著上升,并且SiPK1、SiPK4启动子区域都含有较多的MBS元件,说明SiPK1和SiPK4极有可能参与谷子干旱胁迫响应,并且SiPK4在根中表达量较高。[结论]SiPK4可能通过调控谷子根部发育参与根部对干旱胁迫的应答反应,可作为抗旱相关的候选基因。 相似文献
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Although type 2 immune responses contribute to allergy and asthma, these responses are essential for clearing intestinal helminth infestations by mechanisms that include increased epithelial shedding. We show that T helper 2 cells (T(H)2), but not other T cell subsets, express amphiregulin, a member of the epidermal growth factor (EGF) family. EGF receptor ligands directly induce epithelial cell proliferation, and lack of amphiregulin delayed expulsion of the nematode Trichuris muris. This newly recognized link between T(H)2 cells and epithelial proliferation should help in planning therapeutic interventions for helminth infections and other diseases that involve both cell proliferation and allergy, such as asthma. 相似文献
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目的观察降糖益肾方对高脂饮食转基因2型糖尿病MKR鼠血糖、血胰岛素及肾皮质中胰岛素受体、磷脂酞肌醇-3一激酶蛋白表达的影响、方法选取MKR鼠40只经鉴定后,随机分为MKR鼠组、MKR鼠高脂组、降糖益肾方组和糖适贝那组〔MKR鼠组用基础饲料喂养,MKR鼠高脂组、降糖益肾方组和糖适贝那组用高脂饲料喂养,连续喂养8周后,降糖益肾方组给予降糖益肾方,糖适贝那组给予糖适平加贝那普利,同时MKR鼠组和MKR鼠高脂组分别给予蒸馏水灌胃4周〔4周后处死小鼠收集标本,免疫组织化学SABC法检测肾小球中胰岛素受体1(IRS-1),磷脂酞肌醇-3一激}(PI-3K)的蛋白表达〔结果降糖益肾方明显降低高脂饮食MKR鼠肾小球中IRS-1和PI-3 K的蛋白表达水平,与MKR鼠高脂组比较,差异有统计学意义(P<0.01)、结论降糖益肾方改善糖尿病肾病系膜细胞增殖的机制可能与千预胰岛素信号通路有关、 相似文献
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本研究前期工作发现在一个遗传性先天性白内障家系中,γD晶体蛋白发生了P23T突变.因此本研究对γD晶体蛋白及其突变体进行了氨基酸序列分析,结构域预测及立体结构模拟等生物信息学研究,以探讨P23T突变对γD晶体蛋白结构与功能的影响.研究结果表明:P23T突变可能影响人γD晶体蛋白与钙离子的结合,导致晶状体内钙离子动态失衡;可以使蛋白分子间形成氢键,降低晶体蛋白溶解度;并使蛋白质表面局部极性的改变,影响蛋白与其它分子的结合. 相似文献
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