甲亢与甲减患者血浆同型半胱氨酸水平和MTHFR基因多态性研究

本研究观察了 5 0名正常人 ,3 2例甲状腺功能减退 (甲减 )患者和 48例甲状腺功能亢进 (甲亢 )患者血浆同型半胱氨酸 (Hcy)水平和 5 ,10 亚甲基四氢叶酸还原酶 (MTHFR)基因的多态性。与正常组相比 ,血浆Hcy水平在甲减组升高 (P <0 .0 1) ,而在甲亢组降低 (P <0 .0 5 ) ;在不同甲状腺功能人群中血浆Hcy水平与FT4水平呈负相关 (r =-0 .3 5 ,P <0 .0 1)。在 3组对象中 ,MTHFR均以C/C基因型为主 ,各基因型 (C/C ,C/T ,T/T)、各等位基因 (C ,T)分布差异无显著性 ,但各组中T/T基因型者血浆Hcy水平均高于同组的其它基因型 (P <0 .0 1)。     

不同甲状腺功能患者血浆总同型半胱氨酸水平的临床研究

目的 了解不同甲状腺功能用者血浆总同型半胱氨酸水平，探讨其与甲状腺功能的相关性。方法 收集12例甲状腺功能减退(甲减)患者、28例甲状腺功能亢进(甲亢)患者及30例正常体检人群的血浆，用高效液相色谱法测定总同型半胱氨酸水平，用放射免疫法测定叶酸和VitBl2，酶法测定胆固醇。结果 甲减组总同型半胱氨酸和胆固醇水平较正常对照组显著升高(P＜0.01)，甲减组叶酸水平较正常对照组降低(P＜0．01)；甲亢组总同型半胱氨酸和胆固醇水平较正常对照组降低(P＜0．01)，叶酸水平在此两组间无显著性差异(P＞0．05)；甲减组总同型半胱氨酸较甲亢组显著升高(P＜0．01)，甲减组胆固醇水平较甲亢组显著升高(P＜0．01)，甲减组叶酸水平较甲亢组显著降低(P＜0．01)；三组间VitBl2水平均无显著性差异(P＞0．05)。不同甲状腺功能人群血浆总同型半胱氨酸与其游离T4呈负相关。结论 血浆总同型半胱氨酸水平可能对判断甲状腺功能有辅助作用，甲减思者高同型半胱氨酸血症是其易思心血管疾病的一个独立危险因素。     

太原地区健康体检人群甲状腺功能紊乱患病情况调查

目的　调查太原地区人群中甲状腺功能紊乱的患病率。方法　测定太原地区 812 5名体检人群的TSH ,然后再测定FT3、FT4 和甲状腺抗体。结果　在此体检人群中 ,甲状腺功能亢进(甲亢 )患病率为 1.2 0 % ,亚临床甲亢患病率为 0 .87% ,甲状腺功能减退 (甲减 )患病率为 1.0 3 % ,亚临床甲减患病率为 0 .95 %。各种甲状腺功能紊乱的患病率女性均高于男性 (P <0 .0 5～ <0 .0 1)。结论　报道太原地区人群中甲状腺功能紊乱的患病率 ,无论是甲亢和亚临床甲亢或甲减和亚临床甲减 ,女性的患病率均高于男性     

老年甲状腺功能异常患者糖脂代谢特征及与氧化应激的关系

目的探讨老年甲状腺功能异常状态下糖、脂代谢特征及其与氧化应激的关系。方法选择在该院确诊的老年甲状腺功能异常患者104例,甲亢组54例,甲减组50例,健康组(对照组)50例;青年甲状腺功能异常患者98例,甲亢组51例,甲减组47例,均行糖耐量试验(OGTT)并测定血脂,游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺素(STSH)等甲状腺功能指标,空腹血浆测定丙二醛(MDA)和超氧化物歧化酶(SOD),氧化型低密度脂蛋白(OX-LDL)水平,并进行比较分析。结果老年甲亢组1 h血糖(PG)、2 h PG明显高于对照组(P0.05),1 h PG明显高于青年甲亢组(P0.01)。老年甲亢血脂各组分均低于对照组(P0.05或P0.01);除血清高密度脂蛋白-胆固醇(HDL-C)和载脂蛋白(Apo A)1外,其余指标均高于青年组(P0.05或P0.01)。老年甲减患者甲减组HDL-C低于老年对照组(P0.05),除Apo A1外,其余血脂指标均高于老年对照组(P0.05或P0.01);总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、Lp(a)明显高于青年甲减组(P0.05或P0.01)。老年甲亢组MDA、SOD明显高于老年对照组和青年甲亢组(P0.01),MDA与FT4独立相关。老年甲减组MDA、SOD、OX-LDL显著高于老年对照组,MDA、OX-LDL明显高于青年甲减组(P0.01),MDA与LDL-CFT4独立相关。老年和非老年甲亢组、甲减组SOD/MDA均显著低于对照组,老年组低于青年组。结论老年甲亢患者氧化应激发生于氧化损伤程度与糖脂代谢紊乱有关,甲减患者主要与脂代谢紊乱有关。     

老年人不同甲状腺功能状态下脂代谢特征与氧化应激的关系

目的 探讨老年人不同甲状腺功能状态下脂代谢特征与氧化应激的关系.方法 初诊老年甲状腺疾病患者86例[甲状腺功能亢进(甲亢)47例,甲状腺功能减退(甲减)39例]、非老年甲状腺疾病患者83例(甲亢43例,甲减40例)和老年健康对照组20例.检测空腹血浆丙二醛(MDA)和超氧化物歧化酶(SOD),氧化型低密度脂蛋白(OX-LDL)水平,同时测定血脂指标及甲状腺功能,计算SOD/MDA比值.结果 老年甲亢组血脂各组分均高于非老年甲亢组、低于老年对照组(P＜0.05或P＜0.01);老年甲亢组与非老年甲亢组、老年对照组比较,丙二醛[分别为(10.23±6.29)、(7.37±4.58)μmol/L和(3.66±2.53)μmol/L]、游离脂肪酸(FFA)[分别为(0.86±0.58)、(0.61±0.46)mmol/L和(0.45士0.12)mmol/L]和SOD显著升高(P＜0.01或P＜0.05).老年甲减组与非老年甲减组和老年对照组比较,MDA[(9.03±5.98)、(6.59±3.18)μmol/L和(3.66±2.53)μmol/L]、OX-LDL[(387.36±71.04)、(355.22±45.01)μg/L和(324.53±56.19)μg/L]及部分血脂组分均显著增高(P＜0.05或P＜O.01).老年甲亢组、甲减组SOD/MDA比值均低于老年对照组和非老年组(均为P＜0.01).多元回归分析,甲亢组游离甲状腺素(FT4)和FFA是影响MDA的因素,甲减组非HDL-C和LDL-C与MDA独立相关.结论 初诊老年甲亢和甲减患者氧化应激增强,氧化损伤程度与脂代谢紊乱有关.     

不同甲状腺功能状态下游离脂肪酸与胰岛素抵抗的关系

44例甲状腺功能亢进症(甲亢)、23例甲状腺功能减退症(甲减)和30例甲状腺功能正常人的研究显示,甲亢患者存在胰岛素抵抗,甲亢和甲减患者HOMA-IR与游离三碘甲状腺原氨酸(FT3)和游离甲状腺素(FT4)正相关,甲状腺功能正常者HOMA-IR与游离脂肪酸正相关。     

甲状腺功能异常新型冠状病毒感染临床应对指南

<正>近期,新型冠状病毒(新冠)感染高峰在全国多地出现。甲状腺功能(甲功)亢进症(甲亢)和甲功减退症(甲减)是常见病,导致甲亢的最常见病因是Graves病,甲减的最常见病因是桥本甲状腺炎,两者均为自身免疫性甲状腺疾病^[1-2]。新冠感染除直接破坏甲状腺外,     

甲状腺疾病患者直肠肛门生理功能异常研究

25例甲状腺功能亢进(甲亢)伴腹泻和14例甲状腺功能减退(甲减)伴便秘患者的直肠肛门生理功能测定显示，甲亢患者肛管静息压和收缩压，排便初始感觉阈值和最大直肠耐受容量明显低于21例正常对照组者。甲减患者这些测定值与对照组差异无显著性。     

补碘对缺碘机体甲状腺功能及亚临床性甲状腺疾病发病的研究

目的研究补碘对缺碘人群甲状腺功能及甲状腺疾病发病的影响。方法动态观察了缺碘机体口服碘油前后甲状腺激素水平及其异常值变化和受检者的临床表现。结果补碘使缺碘人群的甲状腺肿大率和患病率显著下降．但早期引起缺碘机体甲状腺激素水平异常变化导致甲状腺功能紊乱，后期因缺碘造成的甲状腺功能高代偿状态趋于正常。补碘前TSH和FT3高于正常值上限的比例均明显多于低于下限的比例，FT4低于下限的比例则明显低于高于上限的比例。补碘3个月TSH和FT3高于上限的比例均明显下降．低于下限的比例则均明显增多；6、12个月FT4高于上限的比例显著增多。补碘前临床甲亢、甲减和甲状腺瘤的检出率分别为0．1l％、0．06％和0．17％，亚临床甲减检出率为1、4％。3、6、12个月的流行病学调查均未发现有甲状腺疾病新发病例．但是亚临床甲亢的检出率则分别升为5．1％、9．4％、6．0％且多发于成年女性甲状腺肿患者和补碘12个月内，亚临床甲减的检出率分别为16、5％、1．6％、2．4％，且多发于成年女性和补碘3个月内。结论补碘虽未增加缺碘人群临床甲亢或甲减发病率，但早期可造成部分机体甲状腺功能紊乱出现亚临床甲亢和甲减发病率一过性升高；其检出率与性别、年龄、有无甲状腺肿和补碘时间有关。     

甲状腺功能与心血管疾病的关系研究

目的:探讨甲状腺功能与心血管疾病的关系。方法:选择在住院期间测定甲状腺功能的患者980例,根据甲状腺功能分为甲状腺功能正常组(正常组,930例),亢进组(甲亢组,18例)及减退组(甲减组,32例),分析3组临床资料,比较血脂,凝血功能各指标。结果:与正常组比较,甲亢组的房颤发生率显著升高,高血压,心功能不全发生率显著降低;TC、TG、LDL-C、HDL-C水平显著降低,部分活化凝血酶原时间显著延长,P均<0.01;甲减组冠心病发生率显著升高,TG、HDL-C水平显著升高,TC、LDL-C水平显著降低,P均<0.01;与甲亢组比较,甲减组高血压、冠心病发生率显著升高,房颤发生率显著显著降低P<0.05或<0.01;TG、LDL-C、HDLC水平显著升高,TC水平显著降低P均<0.01。结论:甲状腺功能与心血管疾病有密切关系,建议甲状腺功能检查作为心血管患者的常规测定,及甲状腺功能异常者的随访指标。     

Troglitazone improves GLUT4 expression in adipose tissue in an animal model of obese type 2 diabetes mellitus

Troglitazone has been shown to improve peripheral insulin resistance in type 2 diabetic patients and animal models. We examined the effect of troglitazone on the expression of glucose transporter 4 (GLUT4) in muscle and adipose tissue from Otsuka Long-Evans Tokushima Fatty (OLETF) rat, an animal model of obese type 2 diabetes mellitus. In addition, the effects of troglitazone on GLUT4 translocation and on glucose transport activity in adipocytes were also evaluated. Muscle and adipose tissues were isolated from 35-week-old male troglitazone-treated and untreated OLETF rats at a dose of 150 mg/kg per day for 14 days. In skeletal muscle, the protein and mRNA levels of GLUT4 were not significantly different between OLETF and control rats and they were not affected by troglitazone. On the other hand, GLUT4 protein and mRNA levels in adipose tissue from OLETF rats were significantly decreased (P<0.01) compared with control rats and they were significantly increased (1.5-fold, P<0.01) by troglitazone. Troglitazone had no major effect on GLUT4 translocation in adipocytes, but it significantly increased (1.4-fold, P<0.05) the basal and insulin-induced amounts of GLUT4 in plasma membrane (PM) in adipocytes from OLETF rats. Consistent with these results, the basal and insulin-induced glucose uptakes in adipocytes from troglitazone-treated OLETF rats were significantly increased (1.5-fold, P<0.05) compared with untreated OLETF rats. Our results suggest that troglitazone may exert beneficial effects on insulin resistance by increasing the expression of GLUT4 in adipose tissue.     

酒精联合高脂饮食对大鼠胰岛素敏感性的影响及其分子机制

研究酒精和高脂对大鼠胰岛素敏感性的影响.测大鼠血糖、血胰岛素和葡萄糖转运蛋白4(GLUT-4)mRNA及蛋白表达水平.结果 示各剂量组血糖、胰岛素抵抗指数升高(均P<0.05),GLUT-4mRNA及蛋白表达显著降低(均P<0.05).     

胰岛素促进在体犬心肌GLUT1移位及其意义

目的 :观察胰岛素能否刺激心肌葡萄糖转运子 1（GL UT1）移位和葡萄糖摄取。方法 :利用自动分析仪测定生理代谢参数 ,应用免疫印迹和免疫荧光法检测 GL UT1。结果 :胰岛素使心肌细胞质膜 GL UT1增加 [从 （42± 5 ） %至 （6 3± 8） % ,P<0 .0 5 ]。细胞器膜 GL U T1则相应减少 ,同时伴随葡萄糖摄取量增加 （P<0 .0 1）。结论 :胰岛素刺激引起 GL UT1移位 ,使心肌葡萄糖摄取增加。应用胰岛素有助于增加心肌葡萄糖的摄取和利用。     

Glucose rapidly decreases plasma membrane GLUT4 content in rat skeletal muscle

We have previously demonstrated that chronic hyperglycemia per se decreases GLUT4 glucose transporter expression and plasma membrane content in mildly streptozotocin- (STZ) diabetic rats (Biochem. J. 284, 341-348, 1992). In the present study, we investigated the effect of an acute rise in glycemia on muscle GLUT4 and GLUT1 protein contents in the plasma membrane, in the absence of insulin elevation. Four experimental groups of rats were analyzed in the postabsorptive state: 1. Control rats. 2. Hyperglycemic STZ-diabetic rats with moderately reduced fasting insulin levels. 3. STZ-diabetic rats made normoglycemic with phlorizin treatment. 4. Phlorizin-treated (normoglycemic) STZ-diabetic rats infused with glucose for 40 min. The uniqueness of the latter model is that glycemia can be rapidly raised without any concomitant increase in plasma insulin levels. Plasma membranes were isolated from hindlimb muscle and GLUT1 and GLUT4 proteins amounts determined by Western blot analysis. As predicted, STZ-diabetes caused a significant decrease in the abundance of GLUT4 in the isolated plasma membranes. Normalization of glycemia for 3 d with phlorizin treatment restored plasma membrane GLUT4 content in muscle of STZ-diabetic rats. A sudden rise in glycemia over a period of 40 min caused the GLUT4 levels in the plasma membrane fraction to decrease to those of nontreated STZ-diabetic rats. In contrast to the GLUT4 transporter, plasma membrane GLUT1 abundance was not changed by the acute glucose challenge. It is concluded that glucose can have regulatory effect by acutely reducing plasma membrane GLUT4 protein contents in rat skeletal muscle. We hypothesize that this glucose-induced downregulation of plasma membrane GLUT4 could represent a protective mechanism against excessive glucose uptake under hyperglycemic conditions accompanied by insulin resistance.     

Elevated GLUT 1 level in crude muscle membranes from diabetic Zucker rats despite a normal GLUT 1 level in perineurial sheaths

Summary Recently, we demonstrated that approximately 60 % of GLUT 1 in a crude membrane fraction of rat skeletal muscle originates from perineurial sheaths. To study the in vivo regulation of GLUT 1 expression in different tissues in muscles, we measured the level of GLUT 1 in crude muscle membranes and in perineurial sheaths in diabetic (fa/fa) Zucker rats and lean controls, with and without metformin treatment. The GLUT 1 concentration in perineurial sheaths was identical in all four groups of rats, both when measured by quantitative immunofluorescence and by immunoblotting and densitometry. In a fraction of crude membranes of soleus muscles GLUT 1 expression was more than two-fold higher in (fa/fa) rats than in lean controls (p<0.005). Metformin treatment significantly elevated GLUT 1 in control rats (p<0.05) and tended to decrease GLUT 1 in diabetic rats (p<0.075). The expressions of GLUT 1 and GLUT 4 in crude muscle membranes were inversely correlated (p<0.01), and GLUT 1 expression correlated positively with fasting glucose (p<0.05). In conclusion, GLUT 1 expression in perineurial sheaths is unaffected by alterations in glucose homeostasis and by the genes responsible for obesity and diabetes in the Zucker rat. GLUT 1 expression in a crude membrane fraction of soleus muscle is increased in the diabetic animals, likely due to an increased expression in muscle cells proper. [Diabetologia (1994) 37: 443–448] Received: 17 June 1993 and in revised form: 19 November 1993     

姜黄素促进骨骼肌GLUT4转位改善糖尿病大鼠胰岛素抵抗

目的:研究姜黄素对STZ诱导糖尿病大鼠骨骼肌胰岛素抵抗的影响及其机制。方法:雄性SD大鼠腹腔注射STZ诱导糖尿病大鼠模型。成模大鼠分为糖尿病组(DM),糖尿病＋姜黄素组(DM＋Cur),糖尿病＋缓冲液对照组(DM＋NC)。以正常SD大鼠为正常对照组(NC)。DM＋Cur组予姜黄素灌胃治疗,DM＋NC组给予等体积缓冲液灌...     

Irisin通过激活AMPK促进C2C12细胞葡萄糖摄取

目的研究鸢尾素(irisin)对C2C12细胞葡萄糖摄取的影响及机制。方法将C2C12细胞分为:Control组,不同浓度的irisin组(分为0.1μg/ml,0.3μg/ml和1μg/ml组),高糖/高脂(HG/HF)处理组,HG/HF+不同浓度的irisin组(分为0.1μg/ml,0.3μg/ml和1μg/ml组),Control+Scramble siRNA组,HG/HF+AMPKα2 siRNA组,HG/HF+scramble siRNA组,HG/HF+scramble siRNA+irisin组,HG/HF+AMPKα2 siRNA+irisin组。采用荧光葡萄糖(2-NBDG)检测细胞的葡萄糖摄取;Western blot检测细胞葡萄糖转运体4(GLUT4)转位情况和AMPK磷酸化水平。结果 (1)与Control组相比,HG/HF组C2C12细胞葡萄糖摄取降低(P0.05),不管是否经过高糖处理,Irisin均增加C2C12细胞葡萄糖摄取(P0.05或P0.01)。与Control组相比,HG/HF降低鼠骨骼肌细胞膜GLUT4表达(P0.01),Irisin显著增加HG/HF孵育骨骼肌细胞细胞膜GLUT4表达(P0.01);(2)与Control组相比,HG/HF降低C2C12细胞细胞膜AMPK磷酸化水平(P0.05),在Control组及HG/HF组,Irisin显著增加骨骼肌细胞AMPK的磷酸化水平(P0.05);(3)与HG/HF+scramble siRNA+irisin组相比,HG/HF+AMPKα2 siRNA+irisin转染组细胞葡萄糖摄取及细胞表面GLUT4表达均显著减少(P0.05或P0.01)。结论 Irisin通过激活AMPK促进小鼠骨骼肌细胞葡萄糖摄取。     

Impaired hepatocyte glucose transport protein (GLUT2) internalization in chronic pancreatitis

Chronic pancreatitis (CP) is associated with impaired glucose tolerance and with reduced hepatic sensitivity to insulin. We have previously shown that in normal and sham-operated rats, insulin suppresses hepatic glucose production, and this suppression is associated with a decrease in the hepatocyte plasma membrane-bound quantity of the facilitative glucose transport protein GLUT2. The insulin-mediated reduction in membrane-bound GLUT2 is impaired in CP, and may play a role in the glucose intolerance associated with CP. To determine whether GLUT2 is actively internalized and whether this mechanism is disordered in CP, livers from fed and fasting rats in whom CP had been induced 2-3 months earlier by pancreatic duct oleic acid infusion, and in sham-operated (sham) rats, were fractionated to yield endosome (E)- and plasma membrane (PM)-enriched fractions. Forty-five minutes after duodenal intubation alone (fasting) or intubation plus duodenal feeding, livers were removed, homogenized and ultracentrifuged, and microsomal pellets were separated by sucrose density gradient ultracentrifugation. GLUT2 content of fractions was determined by Western blotting and scanning densitometry. The E:PM ratio of GLUT2 increased from 0.68 +/- 0.11 (mean +/- SEM) in fasting sham livers (n = 8) to 1.04 +/- 0.09 in fed sham livers (n = 8; p < 0.05). However, there was no change in the E:PM ratio of GLUT2 in CP livers after duodenal feeding (0.90 +/- 0.12 vs. 0.86 +/- 0.10; n = 8,8; p = NS). To test our findings using confocal laser scanning microscopy, liver specimens from fed and fasting CP and sham rats were minced, fixed in 4% paraformaldehyde, sectioned, and stained with rabbit antirat GLUT2 antibody followed by rhodamine-labeled secondary antibody. GLUT2 was quantified by mean pixel intensity in an 8 x 16-pixel area of PM and a 16 x 16-pixel area of cytosol (CYT) in each of 30 random cells/field (400x) in each of three rats per group. As in the fractionation study, duodenal feeding increased the CYT:PM ratio of GLUT2 from 0.75 +/- 0.01 in fasting sham liver to 0.86 +/- 0.01 in fed sham liver (p < 0.0001), while the CYT:PM ratio in CP remained unchanged. We conclude that feeding induces a shift in GLUT2 from the plasma membrane to the endosomal pool. The feeding-induced internalization of GLUT2 is absent in livers from rats with CP and may play a role in the glucose intolerance associated with CP.     

Glucose Transporters and Glucose Utilization in Rat Brain after Acute Ethanol Administration

In the normal adult brain, glucose provides 90% of the energy requirements as well as substrate for nucleic acid and lipid synthesis. In the present study, effects of ethanol on glucose transporters (GLUT) and glucose utilization were examined in rat brain. Male Sprague-Dawley rats weighing 250-300 gms were given either ethanol 3 gm/kg BW or saline IP 4 hrs prior to the animal sacrifice and removal of the cerebral cortical tissue. The cortical plasma membranes analyzed by cytochalasin B binding assay showed a decrease in GLUT number but not in GLUT affinity in the ethanol treated rats as compared to the control rats. The estimated Ro values were 70 ± 8.9 Vs 91 ± 8.9 pmoles/mg protein (p < 0.05 N=4) and the estimated Kd values were 0.37 ± 0.03 and 0.28 ± 0.05 M (p: NS) in ethanol and control experiments respectively. Immunoblots of purified cerebral plasma membranes and low density microsomal fraction showed 17% and 71% decrease for GLUT1 and 54% and 21% (p<0.05 or less; n=6) for GLUT3 respectively in ethanol treated rats than in control animals. Immunofluoresence studies also showed reduction of GLUT1 immunoreactively in choroid plexus and cortical microvessels of ethanol treated rats as compared to control rats. The effect of ethanol on regional cerebral metabolic rates for glucose (CMR_Gle) was studied using [6-¹⁴C] glucose and showed statistically insignificant decrease in brain glucose utilization. These data suggest that ethanol invivo decrease GLUT number and protein content in rat cerebral cortex     

肺癌肿瘤抑制因子1基因过表达对肝细胞糖脂代谢相关基因表达的影响

探讨肺癌肿瘤抑制因子1(TSLC1)基因表达上调对小鼠肝癌细胞Hepal-6糖脂代谢相关基因mRNA表达的影响.结果 显示,TSLC1基因过表达降低脂代谢基因脂肪酸合成酶(FAS)、乙酰辅酶A羧化酶(ACC)的表达(P<0.05或P<0.01),增加脂肪组织甘油三酯水解酶(ATGL)的表达(P<0.05),对激素敏感脂肪酶(HSL)、葡萄糖转运蛋白(GLUT)1和GLUT4的表达无显著影响,提示TSLC1过表达可能抑制肝细胞的脂肪生成,促进脂肪分解.

Abstract：

The effects of tumor suppressor in lung cancer-1(TSLC1)upregulation on gene expressions involved in glucose and lipid metabolism in Hepa1-6 cells were investigated.The results showed that TSLC1 overexpression decreased fatty acid synthase and acetyl CoA carboxylase expressions(P<0.05 or P<0.01),increased adipose triglyceride lipase expression(P<0.05),and did not change hormone-sensitive lipase,glucose transporter (GLUT)1,and GLUT4 expressions.These results suggest that TSLC1 overexpression may promote lipolysis and inhibit adipogenesis in liver cells.