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张路遥 《中国组织工程研究》2020,24(2):276-281
文题释义:沉默信息调节因子1(silent information regulator 1,SIRT1):是调控能量代谢的关键因子,其通过细胞氧化还原等途径来介导能量代谢、基因转录、细胞衰老等生理学过程。研究发现,SIRT1在调控成骨细胞和破骨细胞分化、增殖和活性上均扮演重要角色。骨代谢:骨的功能是为肌肉收缩提供附着处及保护内脏等重要的生命器官。一般认为骨在细胞水平上是不活跃的,事实上骨的细胞在不停地进行着细胞代谢,不仅骨的细胞之间会相互作用,还存在骨髓中的红细胞生成细胞、基质细胞相互作用,以进行骨的改建和重建。背景:能量代谢调控2型糖尿病骨代谢是近来生命医学领域的研究热点。长期糖、脂等能量代谢的紊乱导致胰岛素抵抗,引发2型糖尿病。而沉默信息调节因子1(SIRT1)作为一种烟酰胺腺嘌呤二核苷酸(NAD+)依赖的组蛋白去乙酰化酶,是调控能量代谢关键因子,还参与骨代谢、基因转录、细胞衰老、凋亡及焦亡等。目的:分析近年来有关SIRT1在运动改善骨代谢中的作用机制的相关文献,研究其现状和研究进展。方法:在PubMed、CNKI等数据库进行检索,中文关键词:SIRT1,运动,2型糖尿病,骨形成,骨吸收;英文关键词:SIRT1, exercise, type 2 diabetes,bone formation, bone resorption。结果与结论:①成骨细胞和破骨细胞的分化和功能发挥以及相互之间的代谢平衡是保障骨代谢稳态的关键。而一旦发生紊乱将会导致骨组织形态结构退化,这也是2型糖尿病并发症骨质疏松发生的重要机制;②能量代谢紊乱是引发2型糖尿病的关键,那么SIRT1作为调控能量代谢关键因子,其可通过Wnt、转化生长因子β等途径介导成骨细胞和破骨细胞分化及功能;③近来,研究发现运动可显著改善2型糖尿病的能量代谢和骨代谢,文章从成骨细胞、破骨细胞出发,通过综述目前国内外相关研究,探究SIRT1在运动改善2型糖尿病骨代谢中的作用机制。ORCID: 0000-0002-3135-9409(张路遥)中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程 相似文献
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BACKGROUND: Type 2 diabetes mellitus is a disease caused by energy metabolism disorder. Muscles and bones participate in the body’s energy metabolism regulation through their endocrine function under the condition of exercise stimulation. Currently there are few studies on the mechanism of “Muscle-Bone” Crosstalk mediated exercise regulating bone metabolism in type 2 diabetes mellitus. OBJECTIVE: By analyzing how exercise regulates the expression level of “Muscle-Bone” Crosstalk secretion-related factors and acting on the pathological reasons of bone tissue, to explore the mechanism of bone metabolism mediated by “Muscle-Bone” Crosstalk exercise in type 2 diabetes mellitus.METHODS:CNKI, WanFang, and PubMed were searched for relevant literatures published in recent 10 years. The keywords were “exercise, type 2 diabetes mellitus, bone metabolism, “Muscle-Bone” Crosstalk, muscle factor” in Chinese and English, respectively. After screening, 50 eligible articles were analyzed and discussed. RESULTS AND CONCLUSION:Some of bioactive factors in muscles and bones act on the bones in an endocrine manner, such as myostatin, bone morphogenetic protein, musclin, etc., and the others act on the bones in a paracrine manner, such as insulin-like growth factor 1, interleukin 6, irisin, etc. These factors participate in the regulation of bone metabolism, balance the bone formation of osteoblasts and bone resorption of osteoclasts in bone tissue, and become the messenger factors of exercise-mediated musculoskeletal system. Exercise is an important means to regulate energy metabolism. Exercise-mediated internal stimulus changes can trigger the signal response of muscle cells and bone cells, activate Wnt, bone morphogenetic protein/Smads, transforming growth factor-β and other signal pathways, thereby regulating the endocrine function of the musculoskeletal system, promoting metabolic adaptation and influencing bone metabolism in type 2 diabetes mellitus. 相似文献
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目的探讨金丝桃苷(HYP)对2型糖尿病性骨质疏松症(T2DOP)大鼠骨质疏松的影响及机制。方法雌性SD大鼠采用高糖、高脂饮食联合低剂量(30mg/kg)链脲佐菌素和双侧卵巢切除术建立T2DOP模型,建模后分为模型组(T2DOP组)、低剂量(50mg/kg)HYP(L-HYP)组、高剂量(100mg/kg)HYP(H-HYP)组和HYP+Sirt1抑制剂EX-527组(100mg/kgHYP+1mg/kgEX-527),每组12只;另取12只大鼠为正常对照(NC)组。给予相应的药物干预3个月后,检测大鼠体重、空腹血糖(FBG)、血清脂质[总胆固醇(TC)、甘油三酯(TG)和低密度脂蛋白胆固醇(LDL-C)]及骨代谢标志物[抗酒石酸酸性磷酸酶5b(TRACP-5b)、I型前胶原氨基端原肽(PINP)、骨钙素(OCN)和I型胶原交联羧基末端肽(CTX-I)]水平;评估骨生物力学特性和骨微结构;苏木精-伊红染色检测骨组织形态学变化;免疫组织化学染色检测骨组织中微管相关蛋白1轻链3(LC3)和beclin-1的表达;RT-qPCR和Westernblot分析LC3、beclin-1、p62和沉默信息调节因子1(Sirt1)/腺苷酸活化蛋白激酶(AMPK)信号通路相关分子的mRNA和蛋白表达。结果与NC组相比,T2DOP组大鼠的体重、血清PINP和OCN水平、最大载荷和弹性模量、骨密度(BMD)、骨连接密度(Conn.D)、骨小梁数(Tb.N)、骨小梁厚度(Tb.Th)、LC3mRNA表达水平、beclin-1mRNA表达水平、Sirt1mRNA表达水平、AMPKmRNA表达水平、LC3蛋白表达水平、beclin-1蛋白表达水平、Sirt1蛋白表达水平、LC3-II/LC3-I比值和p-AMPK/AMPK比值显著降低,FBG、TC、TG、LDL-C、TRACP-5b、CTX-I、骨小梁间隔(Tb.Sp)、p62mRNA表达水平、哺乳动物雷帕霉素靶蛋白(mTOR)mRNA表达水平和p-mTOR/mTOR比值显著升高(P <0.05);与T2DOP组相比,L-HYP组和H-HYP组大鼠体重、血清PINP和OCN水平、最大载荷和弹性模量、BMD、Conn.D、Tb.N、Tb.Th、LC3mRNA表达水平、beclin-1mRNA表达水平、Sirt1mRNA表达水平、AMPKmRNA表达水平、LC3蛋白表达水平、beclin-1蛋白表达水平、Sirt1蛋白表达水平、LC3-II/LC3-I比值和p-AMPK/AMPK比值显著升高,FBG、TC、TG、LDL-C、TRACP-5b、CTX-I、Tb.Sp、p62mRNA表达水平、mTORmRNA表达水平和p-mTOR/mTOR比值显著降低(P <0.05),且H-HYP组优于L-HYP组(P <0.05);EX-527可消除HYP对自噬的诱导作用,并减弱HYP对T2DOP大鼠骨代谢和骨微结构的改善作用。结论HYP可缓解T2DOP大鼠的血脂和血糖失调,进而改善骨代谢和骨微结构,其作用机制可能与激活Sirt1/AMPK信号通路,促进自噬有关。 相似文献
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目的探讨线粒体自噬在运动(Exe)干预2型糖尿病心肌病中的作用及可能机制。方法自发性2型糖尿病Goto-Kakizaki(GK)大鼠随机分为2组:糖尿病组(GK组)和GK+Exe组,每组8只;另增设8只同周龄雄性Wistar大鼠作为对照组(Wistar组)。GK+Exe组大鼠经有氧间歇运动干预8周,每天60min,每周5d。在最后一次运动结束48h后,过夜禁食12h后,将大鼠腹腔麻醉、剖腹,腹主动脉采血,检测空腹血糖(FBG)、空腹胰岛素(FINS)及血清乳酸脱氢酶(LDH)和肌酸激酶(CK)水平。制作心肌透射电子显微镜切片,观察心肌细胞及线粒体的超微结构。Westernblot法测定心肌组织中p-AMPK、p-ULK1、TFEB、PINK1、parkin、LC3-II、LC3-I和p62蛋白表达,并计算LC3-II/LC3-I比值。结果与Wistar组相比,GK组大鼠FBG及血清LDH和CK水平显著升高(P <0.01),FINS水平显著降低(P <0.01);心肌线粒体结构欠缺,有空泡现象,偶见自噬体;心肌p-ULK1表达显著下降(P <0.01),p62表达显著升高(P <0.01)。与GK组相比,GK+Exe组大鼠FBG和血清CK水平显著降低(P <0.05),FINS水平显著升高(P <0.05);心肌线粒体结构基本完整,空泡现象减轻,自噬体形成增多;心肌p-AMPK、p-ULK1、TFEB和parkin表达及LC3-II/LC3-I显著升高(P <0.05或P <0.01),p62表达显著下降(P <0.05)。结论有氧间歇运动对2型糖尿病心肌病具有一定的缓解作用,其机制可能与激活心肌AMPK/ULK1信号通路,提高心肌线粒体自噬有关。 相似文献
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2型糖尿病患者骨代谢生化指标的临床意义 总被引:2,自引:0,他引:2
目的 :探讨 2型糖尿病患者骨代谢生化指标的临床意义。方法 :对 4 0例 2型糖尿病患者及 31例正常人进行血骨钙素 (BGP)、钙 (Ca)、碱性磷酸酶 (ALP) ;尿脱氧吡啶啉 (DPD)、Ca、肌酐 (Cr)测定。结果 :糖尿病组血清BGP较正常对照组明显降低 (P <0 0 5 ) ;尿DPD/Cr比值 ,Ca/Cr比值显著高于正常对照组 (P <0 .0 5 ,P <0 .0 5 ) ;血清Ca、ALP两组无统计学差异。结论 :2型糖尿病患者骨代谢异常引发骨量减少、骨质疏松与骨形成减少和骨吸收增加有关 ;血BGP、尿DPD/Cr、Ca/Cr可作为早期诊断糖尿病骨量减少、骨质疏松敏感的骨代谢生化指标。 相似文献
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目的:探讨2型糖尿病男性患者骨密度与骨代谢生化指标间的关系。方法:选取我科2014年1月至2015年12月入院的2型糖尿病男性患者102例,采用双能X线骨密度仪,测定腰椎(L2~L4)、股骨上端[包括股骨颈(Neck)、华氏三角(Ward)及股骨粗隆(Troch)]和全身的骨密度(bone mineral density, BMD)值;根据T值将这些患者分为骨量正常组(44例)、骨量减少组(36例)和骨质疏松组(29例),采用酶联免疫法测定各组碱性磷酸酶(alkaline phosphatase,ALP)、N-端中段骨钙素(N-MID-OT)、总Ⅰ型胶原氨基端延长肽(type 1 amino-terminal propeptide,tP1NP)和β胶原特殊序列(β-CTX)的浓度,比较三组骨代谢指标的变化,并对BMD与各项骨代谢指标进行相关性分析。结果:随着骨密度的降低,骨代谢指标的水平逐渐增高,其中,N-MID-OT和β-CTX的水平在三组间的差异皆有统计学意义(P<0.05);tP1NP在骨质疏松组和其余两组有统计学差异(P<0.05);ALP在三组间无统计学差异(P>0.05)。骨量减少组中,N-MID-OT与Neck、Troch及全身的BMD呈负相关(r=?0.754,?0.663,?0.743;P<0.05),β-CTX与Ward的BMD呈负相关(r=?0.273;P<0.05);骨质疏松组中, N-MID-OT与所有部位的BMD呈负相关(r=?0.736,?0.562,?0.715,?0.521,?0.436;P<0.05),β-CTX与Neck、Ward及全身的BMD呈负相关(r=?0.532,?0.614,?0.764;P<0.05)。结论:2型糖尿病男性患者骨密度与骨代谢指标呈负相关,两者联合评估有助于早期预防骨质疏松。 相似文献
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自噬是细胞内降解细胞成分的主要通道,对生物体的生存、分化、发育和维持其动态平衡具有关键作用。自噬机制既可作为免疫系统清除细胞内病原物质的效应器,也可作为模式识别受体或细胞因子的效应器,帮助免疫系统确认病原侵入和细胞转化。更为重要的是,自噬过程还可通过将细胞内物质转移到溶酶体降解并呈递给Ⅱ型MHC分子,与细胞应激和炎症反应耦联,参与调节固有免疫和适应性免疫反应。对自噬参与免疫反应分子机制的研究将加深对免疫反应分子机制的全面了解,为自噬相关疾病防治提供新的机会和途径。 相似文献
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背景:髋部骨折和2型糖尿病是老年人的常见病和多发病,其内在的相互联系有待进一步研究。目的:比较髋部骨折患者合并2型糖尿病与否的骨代谢标志物水平。方法:2014年8月至2020年8月共有743例髋部骨折患者纳入研究,根据是否有糖尿病病史,将其进一步分为2型糖尿病组(118例)和非2型糖尿病组(625例)。收集并比较两组患者的生化指标(空腹血糖、碱性磷酸酶、三酰甘油、总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、血钙和血磷)以及骨代谢参数(总Ⅰ型前胶原N-末端前肽、年龄相关的Ⅰ型交联C-端肽和25-羟基维生素D)。通过Spearman相关分析计算空腹血糖、三酰甘油与骨代谢参数之间的相关性。结果与结论:①2型糖尿病组患者的空腹血糖和三酰甘油水平显著高于非2型糖尿病组(P < 0.001);②此外,2型糖尿病组患者的总Ⅰ型前胶原N-末端前肽(P=0.017)和年龄相关的Ⅰ型交联C-端肽(P=0.007)水平显著低于非2型糖尿病组;③空腹血糖与年龄相关的Ⅰ型交联C-端肽、空腹血糖与总Ⅰ型前胶原N-末端前肽、三酰甘油与总Ⅰ型前胶原N-末端前肽、血钙与25-羟基维生素D的相关系数分别为-0.124(P < 0.001)、-0.174(P < 0.001)、0.075(P=0.04)和0.108(P=0.003);④该横断面研究发现髋部骨折合并2型糖尿病患者的骨转换状态(骨形成和骨吸收)较低;空腹血糖水平与总Ⅰ型前胶原N-末端前肽和年龄相关的Ⅰ型交联C-端肽水平呈负相关;此外,良好的血糖控制可能有利于骨骼代谢并防止髋部骨折后骨折延迟愈合。缩略语:总Ⅰ型前胶原N-末端前肽:total procollagen type 1 N-terminal propeptide,TP1NP;年龄相关的Ⅰ型交联C-端肽:age-related typeⅠcross linked C-telopeptide,CROSSLhttps://orcid.org/0000-0001-6863-4462(孙佳佳)中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程 相似文献
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目的通过建立2型糖尿病骨质疏松大鼠模型,探讨其骨重建特点。方法 雌性Wistar大鼠分为假手术组(NS组);去卵巢组(NOVX组);2型糖尿病假手术组(DS组)和2型糖尿病去卵巢组(DOVX组)。糖尿病组大鼠造模成功后行双侧卵巢切除术,0、4、8和12周测血糖(FPG)、胰岛素(FINS)、雌激素(E2)及血清骨特异性碱性磷酸酶(B-ALP)和抗酒石酸酸性磷酸酶(TRACP5b),同期测定骨密度(BMD)并行成骨和破骨细胞培养。结果 0周时DOVX组的血糖(13.1±4.9)mmol/L明显高于NS组的(4.4±0.6)mmol/L(P<0.05)。4周时DOVX组的BMD为(0.073±0.012)g/cm2明显低于NS组的(0.098±0.016)g/cm2(P<0.05)。4、8和12周时DOVX组的B-ALP与NS组均无差异,而4和8周时DOVX组的TRACP5b明显高于NS组(P<0.05)。4、8和12周时DOVX组的成骨细胞活力与NS组均无差异,而DOVX组的破骨细胞计数明显高于NS组(P<0.05)。结论 2型糖尿病骨质疏松大鼠骨重建特点为骨吸收活跃而骨形成相对减慢。 相似文献
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目的:分析2型糖尿病患者的抑郁症状及其与人格特质、运动行为的关系。方法:选取2型糖尿病患者718人,基于病人健康问卷抑郁自评量表(PHQ-8)、大五人格量表简式版(CBF-PI-B)建立logistic模型,分析抑郁症状与人格特质的关系及运动行为的调节作用。结果:存在抑郁症状的患者161人(22.4%)。神经质与宜人性得分与抑郁症状正向关联(OR=1.08、1.08)。已经开始锻炼、男性、诊断时间较长的患者抑郁症状比例较低(OR=0.44、0.47、0.62),已使用药物/胰岛素的患者抑郁症状比例较高(OR=2.23);参与锻炼会降低神经质与抑郁症状之间的关系(OR=0.95),但对宜人性与抑郁之间的关系无影响(P>0.05)。结论:糖尿病患者的神经质、宜人性与抑郁症状关系密切;参与运动可以有效减弱神经质对抑郁的影响。 相似文献
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Type 2 diabetic mellitus (type 2 DM) comprises more than 95% of all Taiwanese patients with DM. Tumor necrosis factor-alpha (TNF-alpha) expression is linked with insulin resistance, and is under strong genetic control. The correlation between TNF promoter genotypes and type 2 DM is still controversial, because discrepancies among different studies exist. Ethnic differences play certain roles in these conflicting results, because the distribution of TNF promoter polymorphisms is different among study subjects with different racial origins. Therefore, we examined the relationship between the incidence of type 2 diabetes in Taiwanese and two polymorphisms of the TNF-alpha promoter region (positions -238 and -308) as well as the correlation between these polymorphisms and the patients' biochemical manifestations. Genomic DNA was extracted from peripheral blood cells of 261 Taiwanese patients with type 2 DM and 189 non-diabetic control study subjects, and their TNF promoter G-238A and G-308A polymorphisms were analyzed by PCR-RFLP analysis. No significant association between TNF-alpha G-238A and G-308A polymorphisms with type 2 diabetic incidence was observed. However, associations between TNF-alpha G-238A and low-density lipoprotein-cholesterol and between G-308A promoter polymorphism and high-fasting plasma glucose levels, using multiple linear regression analysis with adjustment for the subjects' age, sex, body mass index and diabetic status, were found. Our results suggested that though TNF-alpha G-238A and G-308A polymorphisms were not involved in the pathogenesis of type 2 DM, type 2 diabetic patients carrying TNFA-A or TNF-308*2 genotype might be more susceptible to diabetic complications such as atherosclerosis. 相似文献
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目的 研究2型糖尿病鼠肝组织骨形成蛋白-9(bone morphogenetic proteins-9,BMP-9)基因转录及蛋白表达的变化.方法 将大鼠随机分为2型糖尿病模型组与正常对照组,分别于造模后5、10、20 d处死,以RT-PCR及Western-blot对肝组织BMP-9基因转录及蛋白表达水平进行检测与分析.结果 2型糖尿病模型组BMP-9基因转录及蛋白表达水平与正常组相比均显著性降低(P<0.05);并且2型糖尿病大鼠5、10、20 d处死组BMP-9基因转录及蛋白表达水平呈逐步下降趋势.结论 2型糖尿病大鼠肝组织BMP-9基因转录及蛋白表达水平较正常显著降低,这一变化可能与2型糖尿病的发生发展相关. 相似文献
15.
目的:探讨2型糖尿病患者合并视网膜病变其骨密度的变化。方法:选择2型糖尿病患者111例,按糖尿病视网膜病变分为糖尿病视网膜病变组和糖尿病眼底正常对照组,采用全自动生化检测仪测定甘油三酯、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、血尿酸,骨密度采由美国Norland公司XR-36型双能X线骨密度仪测定,分别测定腰椎正位(L2、L3、L4)、左侧股骨颈、大粗隆区、Ward’s三角区的骨密度。结果:1)糖尿病视网膜病变组股骨颈、大粗隆区、Ward’s三角区的骨密度低于对照组,差异有统计学意义(P<0.05);而在腰椎正位两者的差异无统计学意义(P>0.05);2)糖尿病患者的骨密度与体重指数、尿酸呈正相关,与年龄、糖尿病病程、甘油三脂、总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇呈负相关。结论:2型糖尿病合并视网膜病变其骨密度降低。 相似文献
16.
Krause MP Hallage T Gama MP Goss FL Robertson R da Silva SG 《International journal of medical sciences》2007,4(5):288-292
BACKGROUND: Diabetes incidence in people with advanced age is increasing at an alarming rate, and for this reason the screening of high-risk individuals such as elderly women is critically important. OBJECTIVE: To analyze the association of adiposity, cardiorespiratory fitness and exercise practice with type 2 diabetes (T2D) in elderly Brazilian women. METHODS: Participated of this cross sectional study 1,059 elderly women (mean 69.5 yr; SD 6.1), who self-reported family history of cardiovascular disease, smoking status, hypertension, and T2D diagnosed previously by a physician. The following independent variables were assessed: exercise practice, body mass index, waist circumference, and cardiorespiratory fitness. Logistic regression analysis was used to investigate the association between each independent variable with T2D using adjusted-models. RESULTS: T2D prevalence was 16%. General and central adiposity were directly associated with T2D, whereas cardiorespiratory fitness was inversely related with T2D. The joint effect of exercise practice and central adiposity showed that inactive women had higher odds ratio for T2D when compared with active ones, within the same WC group. Inactive women with WC > or = 94.0 cm had an odds ratio of 5.8 (95%IC 1.3-25.3). CONCLUSIONS: A direct positive association was found between general and central adiposity, as well as an inverse relation between CRF and exercise practice with T2D. Elderly women who practice exercise regularly had lower odds for T2D. Health professionals should encourage individuals of all ages to engage on regular exercise practice, which could reduce body fatness and may be beneficial in reducing the prevalence of T2D in older ages. 相似文献
17.
Introduction: The objective of this study was to evaluate glucose transport into lymphocytes in healthy subjects and patients with type
2 diabetes mellitus (DM) treated either with diet only or with insulin and to propose peripheral blood lymphocytes as a convenient
model for cellular glucose transport studies.
Materials and Methods: Sixty subjects with type 2 DM, 30 treated with diet only and 30 with insulin, were investigated. Thirty healthy subjects matched
for age, weight, and sex served as a control group. Deoxy-D-glucose, 2-[3H(G)] transport was studied in isolated peripheral blood lymphocytes. Expression of glucose transporters was ascertained by
immunocytochemical identification and by Western blotting.
Results: In lymphocytes from the control group, deoxy-D-glucose uptake increased gradually with the duration of the experiment. In
diabetics treated with insulin, the maximal increase in deoxy-D-glucose uptake was observed after 30 min of the investigation,
followed by a plateau phase. In diabetics treated with diet, deoxy-D-glucose uptake increased slowly during the first 30 min.
The presence of GLUT1 and GLUT3 in lymphocytes was confirmed in this study.
Conclusions: Glucose transport into lymphocytes is altered in type 2 DM. In lymphocytes from diabetics, the dynamics of deoxy-D-glucose
uptake significantly differed from that in healthy subjects. There was also a significant difference between the diabetic
groups, representing different modes of therapy and stages of the disease. Glucose transport into lymphocytes is apparently
influenced by DM as well as by the mode of therapy. We suggest that peripheral blood lymphocytes may become a promising model
for studies on glucose transport in diabetes. 相似文献
18.
Selifanova E. I. Barer G. M. Mkrtumyan A. M. Denisov A. B. 《Bulletin of experimental biology and medicine》2004,138(9):305-307
Crystal aggregations of oral fluid from normal subjects and patients with type 2 diabetes mellitus were examined. Morphological
signs characterizing crystal aggregations of salivary pools from patients with type 2 diabetes mellitus are described and
classified.
Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 9, pp. 345–347, September, 2004 相似文献