葡萄糖-6-磷酸酶催化亚基通过诱导细胞周期阻滞抑制肝癌细胞增殖

目的:葡萄糖-6-磷酸酶催化亚基（G6PC）重组腺病毒,探究G6PC对肝癌细胞增殖及细胞周期调控的影响。方法:构建重组腺病毒AdG6PC,将Huh7细胞及SK-Hep1细胞设为Mock组、AdGFP组、AdG6PC组。采用细胞增殖实验及克隆形成实验观察其对肝癌细胞增殖的影响,transwell实验及划痕实验观察其对肝癌...     

葡萄糖-6-磷酸酶与糖尿病

葡萄糖-6-磷酸酶是肝脏糖异生的两个关键酶之一，该酶的活性变化直接影响肝脏葡萄糖的输出。大量的研究表明，葡萄糖-6-磷酸酶的活性及其基因表达水平在胰岛素抵抗、糖尿病中均明显增加。因此，该酶同胰岛素抵抗、糖尿病高血糖有着密切的关联。葡萄糖-6-磷酸酶作为糖尿病治疗药物的一个潜在靶点正日益成为人们研究的重点。     

葡萄糖-6-磷酸酶与糖尿病

葡萄糖-6-磷酸酶是肝脏糖异生的两个关键酶之一,该酶的活性变化直接影响肝脏葡萄糖的输出。大量的研究表明,葡萄糖-6-磷酸酶的活性及其基因表达水平在胰岛素抵抗、糖尿病中均明显增加。因此,该酶同胰岛素抵抗、糖尿病高血糖有着密切的关联。葡萄糖-6-磷酸酶作为糖尿病治疗药物的一个潜在靶点正日益成为人们研究的重点。     

葡萄糖-6-磷酸酶催化亚基通过诱导细胞周期阻滞抑制肝癌细胞增殖

目的葡萄糖-6-磷酸酶催化亚基(G6PC)重组腺病毒, 探究G6PC对肝癌细胞增殖及细胞周期调控的影响。方法构建重组腺病毒AdG6PC,将Huh7细胞及SK-Hep1细胞设为Mock组、AdGFP组、AdG6PC组。采用细胞增殖实验及克隆形成实验观察其对肝癌细胞增殖的影响, transwell实验及划痕实验观察其对肝癌细胞侵袭和迁移的影响, 细胞周期流式分析过表达G6PC对肝癌细胞增殖周期的影响, 蛋白质印迹法检测过表达G6PC对肝癌细胞周期蛋白表达的影响。结果成功构建重组腺病毒AdG6PC。Huh7细胞及SK-Hep1细胞增殖实验示AdG6PC组增殖细胞数明显低于其他2组(P < 0.05), 克隆形成实验显示AdG6PC组的克隆数明显少于其他2组(P < 0.05), 说明肝癌细胞中过表达G6PC可明显抑制肝癌细胞的增殖能力;transwell实验结果表明细胞AdG6PC组细胞迁移数明显少于其他2组(P < 0.05), 划痕实验结果显示AdG6PC组划痕修复率明显低于其他2组(P < 0.05), 说明过表达G6PC可明显抑制肝癌细胞侵袭和迁移。细胞周期流...     

2型糖尿病患者葡萄糖激酶基因多态性的研究

目的 研究天津地区人群中葡萄糖激酶基因多态性与2型糖尿病的关系。方法 应用聚合酶链反应对天津地区的43例2型糖尿病患者与46名正常对照个体的葡萄糖激酶基因的3’末端--10Kb处的1个(CA)n重复片段的多态性进行了研究。结果 在葡萄糖激酶基因中存在5种等位基因(a、b、c、d、e等位基因)，其中a等位基因频率在对照组30％、糖尿病组16％，两组差异有显著意义(P＝0．026)，e等位基因频率在糖尿病组明显高于对照组，分别为27％和13％，两组差异有非常显著意义(P＝0．011)。在调整年龄、性别和体重指数后，e等位基因仍与2型糖尿病存在特异性关系(P＜0．05)。结论 葡萄糖激酶基因(CA)n重复片段多态性可能是天津地区人群中2型糖尿病的遗传标志。     

老年人2型糖尿病与葡萄糖激酶基因多态性的关系

目的 检测老年人２型糖尿病（ＤＭ２）患者葡萄糖激素（ＧＣＫ）等位基因频率的变化,进而从分子水平探讨ＤＭ及其血管并发症的发病机制。方法 采Ｐ有染成ＥＢ染色法,检测３６～７６岁,ＤＢ２患者１３２例对照组１２８例的ＧＣＫ基因。结果 与健康老年组比较,老年Ｄ Ｚ１等侠基因频率明显升高（４９：２９,Ｐ〈０．０５）,Ｚ等位基因频率则下降（６５：９７,Ｐ〈０．０５）,老年ＤＭ２并发血管病变的比例（６８％）高于非     

葡萄糖激酶调节蛋白P446L基因多态性与甘肃回族2型糖尿病的关系

目的探讨葡萄糖激酶调节蛋白(GCKR)基因P446L多态性与甘肃回族2型糖尿病(T2DM)的相关性及其对糖脂代谢的影响。方法 T2DM患者178例和正常对照者207例,应用PCR-RFLP检测GCKR-P446L基因型,采用氧化酶法或放免法测定血糖、胰岛素及血脂水平。结果①GCKR基因P446L多态性位点的基因型分布和等位基因频率在T2DM组和正常对照组中的分布存在显著差异,且对照组L446等位基因频率明显高于T2DM组,有显著性差异(基因型:χ2=10.598,P=0.001;等位基因:χ2=6.715,P=0.010)。②L446与P446等位基因携带者相比空腹血糖浓度及胰岛素抵抗指数低而三酰甘油浓度高,差异有统计学意义(P0.05)。结论 GCKR-P446L基因多态性与T2DM、胰岛素抵抗及血脂水平相关,L446等位基因可能是T2DM发生的保护因素之一。     

骨骼肌蛋白磷酸酶1调节亚基基因3′非翻译区多态性与2型糖尿病相关性研究

蛋白质磷酸酶 1(ｐｒｏｔｅｉｎｐｈｏｓｐｈａｔａｓｅ 1,ＰＰ1)在胰岛素作用下可通过脱磷酸作用激活糖原合成酶〔1〕,促进葡萄糖摄取和糖原合成〔2〕。ＰＰ1由一个催化亚基 (ＰＰ1ｃａｔａｌｙｔｉｃｓｕｂｕｎｉｔ,ＰＰ1Ｃ)和糖原目标亚基 (又称调节亚基 ) (ｇｌｙｃｏｇｅｎ ａｓｓｏｃｉａｔｅｄｒｅｇｕｌａｔｏｒｙｓｕｂｕｎｉｔｏｆｔｙｐｅ 1,ＰＰ1Ｇ)组成 ,调节亚基正性调节催化亚基的去磷酸化 ,其编码基因被称作ＰＰＰ1Ｒ3基因〔3〕。在胰岛素抵抗状态下 ,胰岛素对ＰＰ1的激活作用减弱 ,从而降低糖原合成酶的活性〔4〕。最近发…     

白细胞介素-6受体基因单核苷酸多态性及单体型与2型糖尿病的相关性研究

目的 探讨白细胞介素-6受体(IL-6R)基因单核苷酸多态性(SNP)及单体型与2型糖尿病的相关性.方法 选择入住本院的88例2型糖尿病(T2DM)患者为2型糖尿病组,以同期体检并糖耐量正常的98例健康自愿者为对照组,采用聚合酶链反应限制性片段长度多态性(PCR-RFLP)方法对IL-6R基因的2个SNP位点予以基因型检测.采用聚类分析方法分析基因多态性特征.结果 2型糖尿病组D358A基因型中A等位基因频率较对照组高,C等位基因频率较对照组降低,差异有统计学意义(P＜0.05).2型糖尿病组-183(G→A)基因型频率与等位基因频率和对照组比较,差异均无统计学意义(P＞0.05).A2-G单体型在两组中最为常见,其频率分布为0.391、0.288(P =0.053).在4种单体型中两组仅C-A1单体型的频率差异有统计学意义,分别为0.103、0.281 (P =0.001).结论 IL-6R基因第9外显子D358A(rs8192284)是种有价值的遗传性标志,C等位基因对2型糖尿病具有保护作用,携带C-A2单体型的人群较易患2型糖尿病.     

2型糖尿病与白细胞介素-10及其基因多态性的关系

<正>糖尿病前期患病率约为24.5%〔1〕。同时糖尿病又可增加严重的老年性疾病风险,比如糖尿病能够增加卒中风险2⁵倍〔2〕,而2型糖尿病(T2DM)患者血糖波动也可以增加动脉粥样硬化斑块风险〔3〕。T2DM发病机制尚未完全阐明,近年来研究认为T2DM可能是细胞因子介导的炎症反应,炎症在糖尿病的发病机制中起媒介作用。血浆中白细胞介素(IL)-10主要来自Th2细胞的分泌,它参与机体的慢性炎性反应,同时以不同     

Effect of potassium on human and rat liver glucose-6-phosphatase

Summary Potassium chloride concentrations of 100–150 mM were shown to inhibit (20–40%) human and rat liver microsomal glucose-6-phosphatase when the substrate was reduced to physiological concentration. When the enzyme was solubilized by treatment of microsomes with Al₂O₃ the inhibition could be observed at greater substrate concentrations. Since potassium deprivation is associated with hyperglycemia in both animals and man, these observations may have physiological significance. Abstract presented to Society for Pediatric Research (Pediat. Res.7, 336, 1973).     

Deletion of the gene encoding the islet-specific glucose-6-phosphatase catalytic subunit-related protein autoantigen results in a mild metabolic phenotype

Aims/hypothesis Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP, now known as glucose-6-phosphatase, catalytic, 2 [G6PC2]) has recently been identified as a major autoantigen in mouse and human type 1 diabetes. Strategies designed to suppress expression of the gene encoding G6PC2 might therefore be useful in delaying or preventing the onset of this disease. However, since the function of G6PC2 is unclear, the concern with such an approach is that a change in G6PC2 expression might itself have deleterious consequences. Methods To address this concern and assess the physiological function of G6PC2, we generated G6pc2-null mice and performed a phenotypic analysis focusing principally on energy metabolism. Results No differences in body weight were observed and no gross anatomical or behavioural changes were evident. In 16-week-old animals, following a 6-h fast, a small but significant decrease in blood glucose was observed in both male (−14%) and female (−11%) G6pc2 ^−/− mice, while female G6pc2 ^−/− mice also exhibited a 12% decrease in plasma triacylglycerol. Plasma cholesterol, glycerol, insulin and glucagon concentrations were unchanged. Conclusions/interpretation These results argue against the possibility of G6PC2 playing a major role in pancreatic islet stimulus secretion coupling or energy homeostasis under physiological conditions imposed by conventional animal housing. This indicates that manipulating the expression of G6PC2 for therapeutic ends may be feasible. Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible to authorised users.     

A formula for quantifying the effects of substrate cycles (futile cycles) on metabolic regulation. Its application to glucose futile cycle in liver as studied by glucose-6-phosphatase/glucokinase determinations

Summary Substrate cycles (SC) are formed by a ‘forward pathway’ (FP) and a ‘backward pathway’ (BP), the difference between FP and BP forming the ‘metabolic flux’ (MF) through the route of which the cycle is part. SC modulate regulatory effects, i.e. amplify or reduce the % change in MF compared to the % change in FP and BP, thus affecting the sensitivity to regulatory factors, including hormones. A formula is given to calculate (with an approximation of ± 0.5) the ‘flux response index’ (FRI), i.e. the factor by which the % change in FP plus the % change in BP must be multiplied to obtain the % change in metabolic flux, when FP and BP undergo opposite, nonunidirectional changes (as is often the case in metabolic regulation). The formula is: FRI = [(FP+BP)/(FP-BP)]/2. By this formula we evaluated the hepatic activities of glucose-6-phosphatase and glucokinase (which roughly reflect hepatic glucose production and uptake, respectively), i.e. the two enzymes that catalyze the cycle between glucose-6-phosphate (glucose-6-P) and glucose. Based on data obtained in normal, nonobese diabetic and obese diabetic subjects as well as in normal, streptozotocin-diabetic, and obese diabetic (ob/ob) mice, we found that FRI was reduced in non-obese diabetic humans and animals whereas it was increased in obese-diabetic humans and mice, compared to normal controls. Thus, diabetes without obesitydecreases, and obesity with diabetesincreases, the sensitivity of the glucose-6-P/glucose cycle to regulatory agents.     

2型糖尿病患者血清生长停滞特异性基因产物6水平的变化及相关因素分析

目的 探讨血清生长停滞特异性基因产物6（GAS6）水平与T2DM、肥胖的相关性及临床意义。方法新诊断T2DM患者（T2DM组）46例和NGT者（NGT组）42名按BMI18．5kg／mz％BMI％24．9kg／m2或≥25k／m2又各自分为正常体重和超重／肥胖亚组。采用ELISA法测定空腹血清GAS6水平。结果T2DM组血清GAS6浓度低于NGT组[（10．63士1．95）VS（14．27±3．82）ng／m1]（P〈0．01）。偏相关分析显示,血清GAS6与BMI、WC、FPG、Hb＆c、C-RP、TNF-a、IL-6呈负相关（r分别为-0．235、-0．266、-0．362、-0．427、-0．268、-0．442、-0．380,Pd0．05或P〈0．01）,与HDL-C呈正相关（r-0．235,P〈0．05）。多元逐步回归分析显示,BMI、HbA1c、TNF-a（β分别为-0．190、-0．483、-0．580）为血清GAS6水平的独立影响因素。结论T2DM患者血清GAS6水平低于NGT者,BMI、HbA1c、TNF-a与GAS6呈独立负相关。     

Decrease in glucokinase and glucose-6-phosphatase and increase in hexokinase in putative preneoplastic lesions of rat liver

Summary Preneoplastic liver lesions were produced in female Wistar rats by oral administration of 2-acetyl-aminofluorene for 165 days succeeded by a carcinogen-free standard diet up to 420 days. During the treatment numerous altered hepatic foci (AHF) and hyperplastic nodules (HN) were detected histochemically by a focal decrease or lack of adenosine-5-triphosphatase and glucose-6-phosphatase (G-6-Pase) activities. In addition, the immunohistochemically demosntrable amount of L-type pyruvate kinase was clearly reduced. The histochemically demonstrated decrease of G-6-Pase was substantiated by microbiochemical determination of the enzyme activity in microdissected material. Moreover, during the experimental period a continuous decrease in glucokinase and an increase in hexokinase was detected microbiochemically within AHF and HN. These alterations indicate, a shift in the carbohydrate metabolism from gluconeogenesis to glucose utilization and pentose-phosphate-pathway for biosynthesis of nucleic acids. Beside other oncofetal markers, HK may be used as indicator of the early stages of liver carcinogenesis.     

护骨素与糖尿病及其血管并发症关系研究进展

糖尿病血管病变是糖尿病主要并发症,护骨素（OPG）与血管疾病密切相关.本文概述OPG的结构、表达调控、生物学作用,探讨OPG与糖尿病及其血管并发症（大、微血管并发症及内皮功能异常）的关系.     

江苏省各级医院2型糖尿病患者口服降糖药物使用情况分析

目的 了解江苏省单用口服降糖药物（OAD）的T2DM患者的用药情况和血糖控制状况。 方法 选取江苏省13个城市各级医院门诊T2DM患者2966例进行横断面研究,以问卷形式收集患者个人信息、病程资料、治疗及合并症情况,检测HbA1c。 结果 单用OAD患者1524例,平均HbA1c（7.0±1.5）%。高脂血症患病率56.2%,高血压患病率41.4%。63.6%患者HbA1c达标（HbA1c〈7.0%）。20-40岁组HbA1c达标率高于41-60、61-80岁组（P〈0.05）。病程≤5年组HbA1c达标率高于5-10、〉10年组（P〈0.05）。双胍类药物在OAD中所占比例最高,且在各级医院所占比例亦最高。 结论 2009年单用OAD患者的HbA1c达标率高于2010年全国达标率,年轻及短病程患者改善尤为明显。双胍类药物在OAD中使用仍占首位。