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肥胖大鼠胰岛素敏感性与肿瘤坏死因子的关系   总被引:1,自引:0,他引:1  
对随机分组的两组大鼠分别饲以普通饲料和高脂饲料。10周后发现高脂饲养组大鼠体重、内脏脂肪组织重量及空腹血TNF-α水平均高于普通饲料组,且出现胰岛素抵抗。结果表明,高脂饮食可诱导大鼠肥胖伴胰岛素抵抗,其胰岛素抵抗的形成可能与TNF-α水平的升高有关。  相似文献   

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The lipid phosphatase SHIP2 controls insulin sensitivity   总被引:17,自引:0,他引:17  
Insulin is the primary hormone involved in glucose homeostasis, and impairment of insulin action and/or secretion has a critical role in the pathogenesis of diabetes mellitus. Type-II SH2-domain-containing inositol 5-phosphatase, or 'SHIP2', is a member of the inositol polyphosphate 5-phosphatase family. In vitro studies have shown that SHIP2, in response to stimulation by numerous growth factors and insulin, is closely linked to signalling events mediated by both phosphoinositide-3-OH kinase and Ras/mitogen-activated protein kinase. Here we report the generation of mice lacking the SHIP2 gene. Loss of SHIP2 leads to increased sensitivity to insulin, which is characterized by severe neonatal hypoglycaemia, deregulated expression of the genes involved in gluconeogenesis, and perinatal death. Adult mice that are heterozygous for the SHIP2 mutation have increased glucose tolerance and insulin sensitivity associated with an increased recruitment of the GLUT4 glucose transporter and increased glycogen synthesis in skeletal muscles. Our results show that SHIP2 is a potent negative regulator of insulin signalling and insulin sensitivity in vivo.  相似文献   

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Diabetes, a disease in which carbohydrate and lipid metabolism are regulated improperly by insulin, is a serious worldwide health issue. Insulin is secreted from pancreatic beta cells in response to elevated plasma glucose, with various factors modifying its secretion. Free fatty acids (FFAs) provide an important energy source as nutrients, and they also act as signalling molecules in various cellular processes, including insulin secretion. Although FFAs are thought to promote insulin secretion in an acute phase, this mechanism is not clearly understood. Here we show that a G-protein-coupled receptor, GPR40, which is abundantly expressed in the pancreas, functions as a receptor for long-chain FFAs. Furthermore, we show that long-chain FFAs amplify glucose-stimulated insulin secretion from pancreatic beta cells by activating GPR40. Our results indicate that GPR40 agonists and/or antagonists show potential for the development of new anti-diabetic drugs.  相似文献   

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Virus-encoded microRNAs (miRNAs) are a new kind of miRNAs that regulate the expression of target gene in host cells or viruses through inducing cleavage of mRNA, repressing translation, etc., and change the processes of host cells or replicate viruses to escape or resist immune surveillance of host and protect viruses themselves. It has become a hot topic to discover viral genes encoding miRNAs and their target genes, and to identify their functions. This review provides background information on the history of virally encoded miRNAs including their genomic distribution, functions and mechanisms. In addition, we discuss the similarities and differences between virus- and host-encoded miRNAs, the future directions of researches in viral miRNAs and their applications in diseases control and therapy.  相似文献   

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MicroRNAs (miRNAs) are short non-coding RNAs of ,-22 nucleotides that play important roles in diverse biological functions including tumor adaption, survival, and metabolism homeostasis in specific tumor microenvironment, such as hypoxia and low pH. Hypoxia is a unique physiological condition during tumor development and progression, which alters a set of hypoxia-mediated miRNAs expression. These hypoxia-mediated miRNAs may exhibit either oncogenic activities or tumor-suppres sive activities, mainly through the regulation of cellular pathways including hypoxia-inducible factors signaling. Acidic tumor microenvironment develops in hypoxic solid tumors due to a combination of predominant glycolytic metabolism (Warburg effect) and poor fluid clearance due to incomplete vascularization. In this review, we summarize our current understanding of the emerging roles of miRNAs in hypoxia and acidic tumor microenvironment.  相似文献   

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Elucidating the signalling mechanisms by which obesity leads to impaired insulin action is critical in the development of therapeutic strategies for the treatment of diabetes. Recently, mice deficient for S6 Kinase 1 (S6K1), an effector of the mammalian target of rapamycin (mTOR) that acts to integrate nutrient and insulin signals, were shown to be hypoinsulinaemic, glucose intolerant and have reduced beta-cell mass. However, S6K1-deficient mice maintain normal glucose levels during fasting, suggesting hypersensitivity to insulin, raising the question of their metabolic fate as a function of age and diet. Here, we report that S6K1-deficient mice are protected against obesity owing to enhanced beta-oxidation. However on a high fat diet, levels of glucose and free fatty acids still rise in S6K1-deficient mice, resulting in insulin receptor desensitization. Nevertheless, S6K1-deficient mice remain sensitive to insulin owing to the apparent loss of a negative feedback loop from S6K1 to insulin receptor substrate 1 (IRS1), which blunts S307 and S636/S639 phosphorylation; sites involved in insulin resistance. Moreover, wild-type mice on a high fat diet as well as K/K A(y) and ob/ob (also known as Lep/Lep) mice-two genetic models of obesity-have markedly elevated S6K1 activity and, unlike S6K1-deficient mice, increased phosphorylation of IRS1 S307 and S636/S639. Thus under conditions of nutrient satiation S6K1 negatively regulates insulin signalling.  相似文献   

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Ubiquitination-dependent mechanisms regulate synaptic growth and function   总被引:21,自引:0,他引:21  
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在无性系 PR107上使用乙烯利刺激针刺采胶长达11年的试验结果,与常规刀割采胶比较:干胶产量平均年增加12.6%,干胶含量只降低1.9个百分点,开割后树围增粗多34.8%,死皮树率少了一半,差异极为显著。且劳力消耗节约,成本降低,有较高的经济效益。  相似文献   

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采用125I-胰岛素标记法研究大鼠肝细胞膜中胰岛素受体与胰岛素的结合性质,用31P-核磁共振法(31P-NMR)研究大鼠肝细胞膜中胰岛素刺激下的胰岛素受体体外自磷酸化,实验结果表明大鼠肝细胞膜胰岛素受体与胰岛素结合的最佳酸度大约为pH=7.5,并且表明大鼠肝细胞膜上的胰岛素受体为高亲和、低容量和低亲和、高容量两型受体.非放射性的31P-NMR波谱法检测到胰岛素刺激下的大鼠肝细胞膜胰岛素受体的体外自磷酸说明所提取纯化的胰岛素受体具有生物活性.  相似文献   

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微量元素及热处理对ZL107组织和性能的影响   总被引:2,自引:0,他引:2  
ZL107合金具有良好的铸造性能和较高的力学性能,应用非常广泛,但目前还不能满足现代工程结构中大型、复杂、高强度重要铸件的要求.实验在原有成分的基础上,通过添加微量合金元素、混合稀土变质和选择合理的热处理工艺来进一步提高ZL107的综合力学性能.实验结果表明,改进后的合金经过金属型浇注、T5处理后的力学性能:σb为324.2 MPa,δ5为4.1%,HBS为102,比原ZL107合金分别提高了19.7%、46.4%和8.0%.改进后的ZL107合金不但具有较高的强度和硬度,而且具有良好的塑性,有望成为大型、复杂、高强度结构铸铝件的优选合金之一.  相似文献   

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107国道新乡段服务水平调查分析   总被引:2,自引:0,他引:2  
服务水平是指驾驶员和乘客对交通运行时,要求达到的服务质量标准。通过用牌照法实测107国道新乡段行车速度,分析道路及收费站的服务水平,提出了一些全封闭公路管理的措施和建议。  相似文献   

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STM32F1系列处理器是ST公司推出的新一代基于cortex-M3内核的ARM处理器,能够满足工业控制、医疗、消费类等领域的应用需求.同时ST公司为STM32F10x系列推出了一套DSP函数库,能够实现常用的数字信号处理.针对STM32F10x系列,提出了一整套FIR滤波器的设计与实现方法.实验表明,在FIR滤波器设计中,整型滤波器系数完全可以替代设计得到的浮点型系数,同时,在采样率为256样点/s的情况下,128阶滤波器得到256点滤波数据的时间仅为1.5 ms,完全满足工业控制系统的设计需求.  相似文献   

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目的:探讨乳突平片在诊断慢性中耳炎中的作用。方法:搜集经手术病理证实的慢性中耳炎105例(107耳),详细分析其X线表现并与手术结果对照。结果:107耳慢性中耳炎中,单纯型中耳2耳、外耳道胆脂瘤2耳、肉芽肿型中耳炎15耳、胆脂瘤型中耳炎88耳,与病理对照比较的诊断符合率为68.9%。结论:乳突平片仍是中耳炎的基本检查手段。  相似文献   

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Czech MP 《Nature》2000,407(6801):147-148
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Cocrystallization of proinsulin and insulin   总被引:4,自引:0,他引:4  
D F Steiner 《Nature》1973,243(5409):528-530
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