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1.
两步法高胰岛素-正常葡萄糖钳夹技术的建立   总被引:1,自引:1,他引:1  
目的 建立两步法高胰岛素 正常葡萄糖钳夹技术。 方法 应用两步法高胰岛素-正常葡萄糖钳夹术(第一阶段胰岛素输注速率为 30 mU·m-2 ·min-1,第二阶段为 120 mU·m-2 ·min-1),评估10名健康女性志愿者的胰岛素敏感性,同时监测钳夹试验过程中循环血内源性升糖激素(胰高血糖素、皮质醇、生长激素)和游离脂肪酸(FFA)浓度变化。 结果 (1)两步法高胰岛素 正常葡萄糖钳夹术第一阶段(60~90 min)和第二阶段(150~180 min) 稳态血胰岛素分别维持在(46±7)mU/L和(218±27)mU/L,稳态葡萄糖利用率分别为(7.2±1.4)mg·kg-1·min-1和(13.1±1.2)mg·kg-1·min-1;(2)钳夹试验过程中,血清胰高血糖素、皮质醇和 FFA水平较基础值均有显著下降,而生长激素和C肽水平无明显改变。 结论 成功建立了两步法高胰岛素 正常葡萄糖钳夹术;钳夹试验过程中高浓度的胰岛素抑制了胰高血糖素、皮质醇的分泌,并减少脂肪分解。  相似文献   

2.
目的应用高葡萄糖钳夹技术评估短期胰岛素强化治疗对新诊断的2型糖尿病(T2DM)患者胰岛素分泌时相的影响。方法对12例正常人及6例新诊断糖尿病患者行高葡萄糖钳夹试验评价胰岛β细胞功能。6例糖尿病患者进行2周胰岛素强化治疗后重复高葡萄糖钳夹试验。结果正常组第一时相胰岛素分泌(1PH)257±36mU/L,第二时相胰岛素分泌(2PH)63±5mU/L,最大胰岛素分泌80±6mU/L。糖尿病组治疗前胰岛素分泌分别为95±19mU/L、34±9mU/L、39±12mU/L显著低于正常组(P均<0·01)。糖尿病组治疗后与治疗前相比,1PH显著改善(135±27vs95±19mU/L,P=0·01),2PH及最大胰岛素分泌量轻度改善,但差异无统计学意义(40±9mU/Lvs34±9mU/L,P=0·09;46±11mU/Lvs39±12mU/L,P=0·08)。结论对新诊断的T2DM患者2周胰岛素强化治疗能够明显改善胰岛素1PH分泌,并对2PH分泌及最大分泌可能也有改善作用。  相似文献   

3.
目的评价高甘油三酯(甘油三酯≥2.3 mmol/L)、正常葡萄糖耐量人群的胰岛素分泌和胰岛素敏感性。方法筛选正常糖耐量的高甘油三酯血症患者12名(高甘油三酯组,HTG组)和性别、年龄、体重指数相匹配的正常糖耐量、正常血脂者12名(正常对照组,NC组),应用高葡萄糖钳夹技术评价胰岛β细胞功能及胰岛素敏感性。结果HTG组和NC组在钳夹过程中胰岛素呈双相分泌,第一时相胰岛素分泌均于4 ~6 min达到高峰,在10 ~30 min下降,之后随钳夹时间延长逐渐升高,稳态期(120 ~150 min)达到最高。HTG组第一时相胰岛素分泌水平低于NC组[(224.7±133.2) mIU/Lvs(252.6±108.9 )mIU/L,P=0.58],但差别无统计学意义;第二时相胰岛素分泌[(98.6±37.7) mIU/Lvs(65.2±20.0 ) mIU/L,P<0.05]和最大胰岛素分泌率[(135.1±45.2) mIU/Lvs(84.5±29.8) mIU/L,P<0.01]均明显高于NC组,胰岛素敏感性指数则显著低于NC组[(9.89±4.05vs21.97±9.62,P<0.01)。结论正常糖耐量的高甘油三酯血症人群中已经出现明显胰岛素抵抗和代偿性胰岛素分泌增加,高葡萄糖钳夹试验中胰岛素分泌曲线异常。  相似文献   

4.
目的观察非诺贝特对高甘油三酯(TG)血症人群的胰岛素抵抗和胰岛β细胞分泌功能的影响。方法正常糖耐量、高TG血症(TG≥12.3 mmol/L)患者12例(HTG组),予非诺贝特200 mg/d治疗3个月,于治疗前后应用高葡萄糖钳夹技术评价胰岛素敏感性和胰岛β细胞功能。并与正常糖耐量、正常血脂志愿者12名(NC组)进行比较。结果HTG组胰岛素敏感性指数(ISI)显著低于NC组;第一时相胰岛素分泌(1PH)稍低于NC组;第二时相胰岛素分泌(2PH)和最大胰岛素分泌(INS120-150)均明显高于NC组。HTG组非诺贝特治疗后,ISI较治疗前显著升高(18.35±1.76 vs 9.40±1.76,P<0.01);1PH变化无统计学意义[(247.7±32.9)mIU/L vs (225.7±36.7)mIU/L,P=0.94];2PH和INS120-150较治疗前降低[分别为(73.2±9.0)mIU/L vs (106.0±11.3)mlU/L,p=0.014;(89.2±8.9)mIU/L vs (141.6±13.8) mIU/L,P=0.005]。结论非诺贝特调脂治疗能显著改善高TG血症人群的胰岛素抵抗及高葡萄糖钳夹试验中的胰岛素分泌。  相似文献   

5.
目的探讨胰岛素及磷脂酰肌醇3-激酶(PI3-K)途径对NO生成的影响。方法检测胰岛素、葡萄糖以及PI3-K活性不可逆的抑制剂(Wortmannin)对培养的人脐静脉内皮细胞(HUVECs)PI3-K表达以及NO、超氧阴离子(O_2~-)产生和内皮型一氧化氮合酶(eNOS)活性的影响。实验分为对照组、10 mU/L胰岛素组、100 mU/L胰岛素组、甘露醇组、5 mmol/L葡萄糖+10 mU/L胰岛素组(5 mmol/L G1组)、25 mmol/L葡萄糖+100 mU/L胰岛素组(25 mmol/L G2组)、50 nmol/L Wortmannin组(50 nmol/L W组)、50 nmol/L Wortmannin+10 mU/L胰岛素组(50 nmol/L W1组)和50 nmol/L Wortmannin+100 mU/L胰岛素组(50 nmol/L W2组)。结果与对照组比较,不同浓度胰岛素组eNOS活性及NO水平显著升高(P<0.01);25 mmol/L G2组、50 nmol/L W组、50 nmol/LW1组和50 nmol/L W2组eNOS活性及NO水平均显著降低,O_2~-生成明显增加(P<0.01);与对照组比较,不同浓度胰岛组、50 nmol/L W组、50 nmol/L W1组和50 nmol/L W2组PI3-K蛋白表达显著升高(P<0.05,P<0.01)。结论 PI3-K信号途径对于促进NO产生、维持血管内皮细胞的正常功能具有重要作用,在高糖、高胰岛素状态下该条途径受损并由此引发内皮功能障碍。  相似文献   

6.
目的 探讨内脂素基因过表达对大鼠胰岛素敏感性和血浆成纤维细胞生长因子21(FGF-21)的影响.方法 构建大鼠内脂素基因重组真核表达质粒,将该质粒转染大鼠.在转染前后采用正糖-高胰岛素钳夹技术评价大鼠胰岛素敏感性变化,并采用放射免疫法测定其血浆FGF-21浓度.结果 在质粒注射后3 d大鼠血清内脂素水平明显升高(1.49±0.06 vs 0.99±0.04,P<0.01);葡萄糖输注率(GIR)[(35.3±1.4 vs 27.6±1.7)mg·kg-1·min-1,P<0.01]较注射前明显升高;基础血浆胰岛素水平明显下降[(14.5±3.7 vs 24.4±6.2)mU/L,P<0.05];总胆固醇、高密度脂蛋白胆固醇明显降低[(1.31±0.10 vs1.76±0.22)mmol/L和(0.59±0.04 vs 0.95±0.15)mmol/L,均P<0.05];血浆FGF-21也降低[(2.25±0.19 vs 2.59±0.23) μg/L,P<0.05];在转染前后基础血糖和血浆脂联素水平无明显变化.结论 内脂素质粒转染使大鼠血浆vsfatin水平升高和FGF-21水平降低,胰岛素敏感性增强.  相似文献   

7.
目的探讨炎性细胞因子白细胞介素1β(IL-1β)、干扰素γ(IFN-γ)对小鼠胰岛β细胞株βTC-6胰岛素分泌功能的影响。方法将βTC-6细胞培养于高糖DMEM培养基,48h后换用无糖KRBH缓冲液培养30min,分别于含0、1.38、5.50和11.10mmol/L葡萄糖的KRBH缓冲液中孵育60min,放射免疫法检测细胞上清液中胰岛素水平(GSIS)。在BTC-6细胞中分别加入不同浓度的IL-1β(0.15、1.50μg/L)和(或)IFN-γ(10、100U/m1),24h后换用无糖KRBH缓冲液培养30min,在含1.38mmol/L葡萄糖的KRBH缓冲液中孵育60min,放射免疫法检测细胞上清液中胰岛素水平。多组间数据比较采用单因素方差分析,两组间数据比较采用t检验。结果βTC-6细胞在1.38mmol/L葡萄糖刺激时胰岛素分泌达高峰,与无葡萄糖刺激时相比差异有统计学意义[(151±14)对(120±4)mU/L,t=-4.215,P=0.006];5.50、11.10mmol/L葡萄糖刺激时胰岛素分泌较1.38mmol/L葡萄糖刺激时明显下降(均P〈0.05)。与单纯1.38mmol/L葡萄糖刺激组相比,IL-1β(0.15μg/L)组[(85.53±5.06)mU/L对(103.11±0.27)mU/L,t=4.897,P=0.039]、IL-1β(1.50μg/L)组[(62.62±0.64)mU/L对(103.11±0.27)mU/L,t=212.66,P〈0.001]葡萄糖刺激下胰岛素分泌水平显著下降,下降程度与IL-1β的剂量呈正相关;与单纯葡萄糖刺激组相比,IFN-γ(100U/m1)组葡萄糖刺激下胰岛素分泌显著下降[(73.2±1.6)对(105.2±1.8)mU/L,t=19.52,P:0.003];与IL-1β(0.15μg/L)组及IFN-γ(100U/m1)组相比,IL-1β联合IFN-γ组葡萄糖刺激下胰岛素分泌显著下降(F=77.38,P〈0.001)。结论IL-1β和IFN-γ对13TC-6细胞的胰岛素分泌功能有抑制作用,且两者间具有协同效应。  相似文献   

8.
检测36例孕24~36周妊娠糖尿病患者和同期30例健康孕妇凌晨3:00、5:00及75 g葡萄糖负荷后血游离脂肪酸和胰岛素水平,比较两组胰岛素敏感性和胰岛素分泌功能.结果提示凌晨及糖负荷后高游离脂肪酸均与妊娠糖尿病患者胰岛素抵抗相关[胰岛素:(7.18±3.19)对(5.05±1.80)mIU/L(3:00)、(8.19±4.42)对(5.31±1.82)mIU/L(5:00)、(59.18±30.85)对(40.52±15.07)mIU/L(糖负荷后);游离脂肪酸:(0.39±0.20)对(0.23±0.11)mmol/L(3:00)、(0.46±0.17)对(0.29±0.12)mmol/L(5:00)、(0.19±0.13)对(0.09±0.06)mmol/L(糖负荷后);均P<0.01],糖负荷后30 min(早期相)的高水平的游离脂肪酸可能与妊娠糖尿病患者早期胰岛素分泌功能缺陷有关.  相似文献   

9.
糖毒性对TC1-6细胞胰升糖素分泌的影响   总被引:1,自引:0,他引:1  
目的 探讨长期糖毒性对胰岛α细胞胰升糖素分泌的影响及其与α细胞胰岛素抵抗的关系.方法 TC1-6细胞(α细胞株)分别培养于含低浓度(5.5 mmoL/L)、中浓度(11.1 mmol/L)和高浓度(25 mmoL/L)葡萄糖的培养基中1~5天,检测胰升糖素分泌及其mRNA表达;加入不同浓度胰岛素6 h后,观察对培养5天的TC1-6细胞胰升糖素分泌的影响并以Western印迹检测高糖对TC1-6细胞Akt磷酸化的影响.结果 (1)与低糖培养相比,中、高浓度葡萄糖培养1天和3天的TC1-6细胞胰升糖素分泌无明显改变,而高糖培养5天时TC1-6细胞的胰升糖素分泌明显增高[(136.80±10.94 vs 78.62±4.72)ng/106细胞,P<0.05];另外,培养5天时胰升糖素mRNA的表达较1天时明显升高(P<0.05);(2)10-7mol/L胰岛素抑制低糖组TC1-6细胞胰升糖素的分泌[(21.59±1.30 vs 55.12±3.86)ng/106细胞],但仅能轻微抑制高糖组胰升糖素的分泌[(106.58±8.53 vs 117.18±10.55)ng/106细胞];当胰岛素增至10-5mol/L时,高糖组胰升糖素的分泌也受到抑制[(46.55±3.72 vs 118.61±10.68)ng/106细胞];(3)加入10-5mol/L胰岛素2h后,两组TC1-6细胞磷酸化Akt水平分别升高180%和70%,但高糖组明显低于低糖组,给予磷脂酰肌醇3激酶抑制剂后两组TC1-6细胞磷酸化Akt水平在低糖组抑制率明显高于高糖组.结论 高糖可增加TC1-6细胞胰升糖素的分泌,其可能的机制与TC1-6细胞胰岛素抵抗有关.  相似文献   

10.
[英]/Vella A…//Diabet es.-2000,49.-611-617   众多研究已证实胰升糖素样肽1(7-36)酰胺(GLP-1)对2型糖尿病患者和健康志愿者的胰岛素分泌均有强的刺激作用,但GLP-1对胰岛素作用和葡萄糖效应的影响还存在诸多争论,以下进行了相关研究。   对象与方法 12名体重稳定且健康状态良好的2型糖尿病患者为研究对象,其中3名口服降血糖药,3名联用胰岛素和二甲双胍,另外6名单用胰岛素治疗,在研究开始前3周和48h分别停用口服药和长效胰岛素。所有研究对象于18:00进入研究中心,摄取标准食物后禁食至研究结束,并静脉输注足量人胰岛素以维持整个晚上血糖正常。于次日晨05:30(-270min)抽静脉血获取血样,06:00(-240min)开始静脉输注生长激素释放抑制因子(120ng.kg-1.min-1)、人生长激素(3ng.kg-1.min-1)和胰升糖素(0.65ng.kg-1.min-1),08:00(-120min)再持续输注[3-3H]葡萄糖(0.12μCi/min)至研究结束,调整滴速使葡萄糖浓度保持在约5.5 mmol/L。餐时葡萄糖输注在10:00(0min)进行,6例续用胰岛素,另外6例模拟非糖尿病患者餐后胰岛素水平曲线,采用随机顺序分别输注GLP-1(1.2pmol.kg-1.min-1)和生理盐水,并分别测定血浆胰岛素、氢化考的松、生长激素、胰升糖素、C-肽和GLP-1浓度。   结果 两组胰岛素浓度在基础量和餐时量的胰岛素输注期间均无差异,平均C-肽浓度及胰升糖素、生长激素浓度也基本相同;但输注GLP-1后明显增加氢化考的松水平,同时还引起GLP-1免疫反应性的增加,输注生理盐水者则无GLP-1免疫反应性的改变。此期间输注GLP-1组和输注生理盐水组各自葡萄糖浓度的峰值[(10.5±0.4)vs(10.6±0.5)mmol/L和(8.1±0.7)vs(8.2±0.5)mmol/L)]和血糖曲线下面积[(1.21±0.16)vs(1.31±0.19)mol/L和(0.47±0.16)vs(0.55±0.11mol/L]均无差异;同时在输注葡萄糖后两组葡萄糖消失迅速增加至相同的比率,两组内源性葡萄糖的产生受抑制也同样相似[基础量的胰岛素:(-2.7±0.3)vs(-3.1±0.2)mmol/kg和餐时量的胰岛素:(-3.1±0.4)vs(-3.0±0.6)mmol/kg]。   讨论 当胰岛素和胰升糖素浓度相匹配时,GLP-1对2型糖尿病患者胰岛素作用或葡萄糖效应的影响都可以忽略不计,这些数据有力地支持GLP-1是通过增加胰岛素分泌、抑制胰升糖素分泌和延长胃排空而不是通过改变胰腺外葡萄糖代谢来改善对血糖的控制。 (易春涛摘 陈智民校)  相似文献   

11.
The immunoneuroendocrine role of melatonin   总被引:19,自引:0,他引:19  
Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.  相似文献   

12.
13.
Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.  相似文献   

14.
Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.  相似文献   

15.
Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.  相似文献   

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Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the Mr range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [125I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (Ka of 4.7 ± 0.2 × 109 M-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of Mr 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.  相似文献   

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PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.  相似文献   

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