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11.
目的探讨免疫抑制剂对体外培养的大鼠胰岛细胞的毒性作用以及抗凋亡基因Bc l-2对胰岛细胞的保护作用。方法腺病毒介导的基因转染后表达Bc l-2的大鼠胰岛细胞和对照胰岛细胞分别加入不同浓度的他克莫司培养基中,48 h后检测胰岛细胞的凋亡率和分泌胰岛素的功能。结果低剂量和高剂量的他克莫司都能诱导胰岛细胞凋亡,减少胰岛素分泌,Bc l-2能抑制凋亡,改善胰岛素分泌。结论他克莫司对体外培养的大鼠胰岛细胞有直接的损害作用,而Bc l-2能防治这种损害作用。 相似文献
12.
球形脂联素、葡萄糖和游离脂肪酸对胰岛β细胞单磷酸腺苷激活的蛋白激酶和乙酰辅酶A羧化酶磷酸化的影响 总被引:1,自引:0,他引:1
目的:探讨不同浓度的葡萄糖和游离脂肪酸对胰岛β细胞内单磷酸腺苷激活的蛋白激酶(adenosine-5'-monophosphate activated protein kinase,AMPK)和乙酰辅酶A羧化酶(acetyl CoA carboxylase,ACC)磷酸化的影响,以及球形脂联素对AMPK和ACC磷酸化的作用.方法:培养INS-1胰岛细胞系,用5 mmol/L葡萄糖和0.25 mmol/L游离脂肪酸处理,确定在不同时间对AMPK和ACC磷酸化的影响;观察不同浓度葡萄糖和游离脂肪酸对AMPK和ACC磷酸化的影响;在葡萄糖和游离脂肪酸存在的条件下观察AMPK的药理激活剂氨基咪唑-4-甲酰胺核苷酸(AICAR)和球形脂联素对AMPK和ACC磷酸化的影响.结果:不同浓度的葡萄糖和游离脂肪酸都能够在60 min时抑制AMPK和ACC的磷酸化水平,采用AMPK的药理激动剂AICAR能够明显升高AMPK和ACC的磷酸化水平.2.5 mg/L球形脂联素可以使基础状态的AMPK和ACC磷酸化水平分别增加23%(P<0.05)和50%(P<0.05).在5 mmol/L葡萄糖的基础上加用球形脂联素使AMPK和ACC磷酸化水平分别增加1.4倍(P<0.05)和3倍(P<0.01),在0.25 mmol/L游离脂肪酸的基础上加用球形脂联素使AMPK和ACC磷酸化水平分别增加3倍(P<0.05)和5倍(P<0.01).结论:在体外培养的胰岛INS-1细胞中,不同浓度的葡萄糖和游离脂肪酸能够降低AMPK和ACC的磷酸化水平,而AMPK的药理激动剂氨基咪唑-4-甲酰胺核苷酸(5'-aminoimidazole-4-carboxamide riboside,AICAR)和2.5 mg/L球形脂联素可以提高AMPK和ACC的磷酸化水平,此作用可以进一步增强胰岛β细胞内的脂肪酸氧化水平,减轻甘油三酯聚集,保护胰岛β细胞功能. 相似文献
13.
目的:观察1型糖尿病(T1DM)患儿行早期胰岛素(INS)持续静脉输注加三餐前皮下注射短效INS强化治疗对胰岛D细胞功能的影响。方法:T1DM并酮症酸中毒(DKA)患儿12例(强化组),采用早期INS持续输注加三餐前皮下注射短效INS强化治疗。连续观察治疗开始及治疗3个月时空腹血糖(FBG)、餐后2h血糖(2hPBG)、糖化血红蛋白(HbA1c)、空腹C肽/FBG(C-P/FBG)及INS用量。比较治疗前后上述指标的差异,TlDM并DKA患儿10例(非强化组),行非持续静脉强化治疗,对比两组治疗开始及治疗3个月时上述指标的差异;观察急性期患儿进入蜜月期的百分率。结果:①治疗3个月时,强化组FBG、2hPBG及HbAlc均较治疗开始时显著改善,且均达到强化治疗目标;C-P/FBG显著升高,达正常范围;3个月时INS用量显著低于急性期;②非强化组FBG、2hPBG、HbA1c均较开始治疗时明显改善,但未达到强化治疗目标;C-P/FBG升高,但未达正常范围;INS用量无明显减少;③两组治疗开始FBG、2hPBG、HbAlc、C-P/FBG比较差异均无统计学意义,但INS用量强化组显著高于非强化组:治疗3个月时强化组2hPBG、HbA1c、INS用量均显著低于非强化组,C-P/FBG显著高于非强化组(约是后者的8.6倍),两者FBG比较差异无统计学意义;④强化组12例中11例进入蜜月期,非强化组仅3例进入蜜月期。两组比较)χ^2=6.50,P〈0.05。站论:早期INS持续输注加三餐前皮下注射短效INS强化治疗儿童T1DM可促进B细胞的修复及再生,使基础C-P/FBG恢复正常。 相似文献
14.
Sylvie Durant Véronique Alves Josiane Coulaud Françoise Homo-Delarche 《Autoimmunity》2013,46(7):449-455
In the Nonobese diabetic (NOD) mouse, a spontaneous model of type 1 diabetes, the pathogenic process is classically thought to start at 3-4 weeks of age with an accumulation of antigen-presenting cells (APC), especially CD11c+ dendritic cells (DC), around the pancreatic islets of Langerhans. Concomitantly, hyperinsulinemia and slight hyperglucagonemia are observed, which may be either the cause or consequence of the initial APC infiltration. To determine whether infiltrating DC can affect islet activity in control (C57BL/6) and NOD mice, we performed experiments in which islets and DC were isolated and co-cultured. We first showed that, immediately after isolation, islets from 8-week-old prediabetic NOD mice had significantly higher insulin and glucagon contents than those from C57BL/6 controls. Moreover, as is the case in vivo, prediabetic NOD mouse islets secrete more insulin in vitro at 11.1 mM glucose than C57BL/6 ones. In DC-islet co-cultures, insulin secretion was significantly increased for NOD mice only, while that of glucagon was not significantly affected. These findings indicate that NOD DC are good candidates for stimulating the NOD mouse g -cell hyperactivity that is observed both in vivo and in vitro, and might, consequently, sensitize NOD islets to an autoimmune attack. 相似文献
15.
16.
Birger Petersson Claes Hellerström Rolf Gunnarsson Arne Andersson 《Acta diabetologica》1973,10(4):725-736
Summary An enzymatic method for isolation of single cells from the islets of Langerhans is described. The isolated cells appeared
well preserved and survived for at least 7 days when maintained in culture. The dry mass of the isolated islet cells was found
to be decreased 30 min after administration of alloxan to obese-hyperglycemic mice. Isolated individual islet cells from obese-hyperglycemic
mice had a higher dry mass than those from their lean litter mates.
Traduzione a cura di G. U. 相似文献
17.
Summary The content of phosphoenolpyruvate (PEP) has been measured in isolated rat islets of Langerhans incubated in vitro. Islet PEP was higher in islets incubated with 16.7 mmol/l glucose than in islets incubated with zero or 2.8 mmol/l glucose. Islet PEP content was also increased in islets incubated with 5 mmol/l D-glyceraldehyde. Mannoheptulose abolished the glucose-induced rise in PEP content but not that elicited by D-glyceraldehyde. These results are consistent with a role for PEP as an intracellular mediator of glucose- and glyceraldehyde-induced insulin release. The kinetics of pyruvate kinase in extracts of rat islets were studied. The maximal extractable activity was considerably higher than known rates of glycolytic flux. The Km values were found to be 0.16 mmol/l for PEP and 0.5 mmol/l for ADP. The control of islet PEP content and the possible role of PEP in insulin release are discussed. 相似文献
18.
胰岛自身抗体与1型糖尿病 总被引:2,自引:0,他引:2
1617例糖尿病患者中自身抗体阳性率29.7%。单一抗体的阳性率明显低于3种抗体联合检测。多种胰岛自身抗体联合检测可提高1型糖尿病早期诊断的敏感性。谷氨酸脱羧酶抗体为成年糖尿病患者预示胰岛素依赖的较好的筛查试验,与酪氨酸蛋白磷酸酶抗体联合检测可达近100%的预报价值;而青少年糖尿病患者则还需检测胰岛细胞抗体。 相似文献
19.
Summary DNA content seems to be an ideal reference parameter for data on secretory function or metabolism of pancreatic islets. The approved fluorometric DNA assay with diaminobenzoic acid (DABA) of Kissane and Robins comprises repeated ethanol extractions of the tissue for removal of lipids from which some DABA-reactive aldehydes may originate. In the present study it is demonstrated that only negligible amounts of DABA-positive material are extractable from islets of Langerhans. Furthermore, it is shown that various substances used in experiments on the endocrine pancreas do not interfere with the DABA-DNA reaction. A modification of the original DABA procedure which does not include ethanol extractions and which is thus more simple and accurate is described for application to pancreatic islets in the absence as well as in the presence of incubation medium. A close linear correlation between islet dry weight and islet DNA content is demonstrated. Islets from rats, normal mice, and ob/ob mice contain 38.3–39.2 ng DNA per g dry weight. 相似文献
20.
《Immunopharmacology and immunotoxicology》2013,35(1):109-122
During the development of the autoimmune disease, insulin-dependent diabetes mellitus (IDDM) islet cell death is thought to be mediated in part by oxygen and nitrogen free radicals and interleukin 1β (IL-1β), secreted by activated macrophages. Free radicals disrupt the homeostasis of biological systems by damaging major constituent molecules such as lipids, proteins, and DNA. Islet cells are quite susceptible to oxidative damage due to low levels of antioxidant enzymes involved in free radical consumption. If IDDM is associated with an imbalance of oxidative stresses and antioxidant responses in islet cells, then it may be possible to ameliorate disease by supplementating antioxidant defenses. In this study, the antioxidants coenzyme Q10 and lipoic acid were able to block IL-1β-mediated inhibition of glucose-stimulated insulin secretion from islet cells at 10? 12 M and 10? 9 M, respectively. 相似文献