慢性间歇低氧对大鼠肝细胞IRS-2、 FoxO1表达的影响

目的 观察慢性间歇低氧条件下,大鼠肝细胞形态学变化及胰岛素受体底物-2 (IRS-2)、叉头框蛋白O1(FoxO1)的蛋白表达,并探讨IRS-2、FoxO1与胰岛素抵抗的相关性.方法 取24只6周龄健康雄性Sprauge-Dawley大鼠,采用随机数字表法分为正常对照组(NC组)、慢性间歇低氧4周组(CIH4组)、慢性间歇低氧8周组(CIH8组),每组8只.CIH4组和CIH8组暴露于间歇低氧舱内:最低氧浓度6％ ～ 8％,持续时间8 h/d.NC组无间歇低氧暴露正常饲养,CIH4组、CIH8组和NC组分别于第4周、第8周及第8周禁食12 h后测定空腹血糖、空腹胰岛素水平,并采用稳态模型评估-胰岛素抵抗指数(HOMA-IR)和胰岛素敏感性指数(ISI)评价胰岛素抵抗,对肝组织行HE染色观察形态学变化,采用免疫组织化学方法测定肝细胞IRS-2、FoxO1蛋白表达,以平均灰度值表示其蛋白表达量,二者成反比关系.结果 与NC组相比,CIH4组、CIH8组空腹血糖、胰岛素、HOMA-IR升高,ISI降低,且CIH8组更为显著,差异有统计学意义(F=50.23 ～90.26,P均＜0.05).与NC组相比,CIH4组与CIH8组IRS-2蛋白表达降低,FoxO1蛋白表达增高且在核内重新分布,CIH8组更为显著,差异有统计学意义(F=69.46,618.94,P均＜0.05).Pearson相关分析显示:HMOA-IR与IRS-2平均灰度值呈正相关(r=0.857,P＜0.05),与FoxO1平均灰度值呈负相关(r=-0.926,P＜0.05),ISI与IRS-2平均灰度值呈负相关(r=-0.823,P＜0.05),与FoxO1平均灰度值呈正相关(r=0.848,P＜0.05).结论 慢性间歇低氧条件下,大鼠肝细胞受损并发生胰岛素抵抗,同时IRS-2和FoxO1蛋白表达异常,且随暴露时间延长肝细胞损伤程度及胰岛素抵抗程度均逐渐加重.     

慢性间歇低氧对大鼠糖代谢及肝脏 TRB3、P-AKT 表达的影响

目的：通过建立慢性间歇低氧(chronic intermittent hypoxia,CIH)大鼠模型,观察CIH 对大鼠糖代谢的影响以及肝脏胰岛素相关信号通路 Tribbles 同源蛋白3(TRB3)、磷酸化蛋白激酶 B (P-AKT)的变化。方法将40只健康雄性 SD 大鼠随机分为5组,每组8只。正常对照组(NC组)、慢性间歇 低 氧 2 周 组(CIH2组)、慢 性 间 歇 低 氧 4 周 组(CIH4组)、慢性间歇低氧6周组(CIH6组)、慢性间歇低氧8周组(CIH8组),实验组每天给予8 h 间歇低氧处理。实验结束后检测5组大鼠空腹血糖,采用酶联免疫吸附试验(ELISA)检测空腹胰岛素,用稳态模型胰岛素抵抗指数(HOMA-IR)系统评价胰岛素抵抗。采用 HE 染色观察各组肝脏组织形态变化,SABC 法免疫组织化学试剂盒检测大鼠肝细胞 TRB3蛋白以及胰岛素信号通路中关键激酶蛋白激酶 B (AKT)磷酸化水平蛋白的表达,以平均灰度值表示 TRB3、P-AKT 的蛋白表达量。结果随着间歇低氧暴露时间延长,各组与 NC 组比较,其空腹血糖水平(F =116.185,P <0.05)、胰岛素水平(F =45.189,P <0.05)、HOMA-IR (F =110.876,P <0.05)、TRB3蛋白表达水平(F =11 5.253,P <0.05)升高,而 P-AKT 蛋 白 表 达 水 平(F =99.553,P <0.05) 降 低,且以 CIH8组 最 为 显 著 (P <0.05)。Pearson 相关分析显示： HMOA-IR 与 TRB3平均灰度值呈负相关(r =-0.828,P <0.05),与P-AKT平均灰度值呈正相关(r =0.903,P <0.05)。结论 CIH 可导致大鼠肝细胞受损,糖代谢异常,发生胰岛素抵抗,并随着间歇低氧暴露时间的延长,胰岛素抵抗程度加重。CIH 使肝脏中 TRB3蛋白表达增加,P-AKT 显著降低,且与 HOMA-IR 具有明显的相关性,TRB3的激活可能在 CIH 所致的糖代谢异常中起重要作用。     

间歇低氧大鼠肝细胞GLUT-2、GCK表达与胰岛素抵抗的相关性研究

目的 检测葡萄糖转运蛋白-2(GLUT-2)、葡萄糖激酶(GCK)在间歇低氧大鼠模型肝细胞中表达的变化,探讨间歇低氧引起胰岛素抵抗的相关机制.方法 24只6周龄健康雄性SpragueDawley(SD)大鼠按照随机数字表法分为对照组、间歇低氧4周组(IH4组)和间歇低氧8周组(IH8组),每组8只.间歇低氧组按预设通气模式每天给予间歇低氧暴露8h,对照组给予间歇压缩空气,暴露时间同IH4组.实验结束后测定各组大鼠空腹血糖、空腹胰岛素,计算稳态模型评估-胰岛素抵抗指数(HOMA-IR)及胰岛素敏感性指数(ISI).免疫组织化学染色观察肝细胞GLUT-2、GCK蛋白表达变化,并利用平均灰度值对蛋白进行定量分析.结果 与对照组相比,IH4组及IH8组空腹血糖、空腹胰岛素、HOMA-IR均升高,ISI均降低,且IH8组更明显(F=161.92、51.46、126.99、83.87,P均＜0.05).与对照组相比,IH4组及I-H8组肝细胞GLUT-2、GCK蛋白表达均降低,且IH8组更显著(F=184.91、240.85,P均＜0.05).Pearson相关分析显示,GLUT-2、GCK平均灰度值与ISI呈负相关(r=-0.886、-0.906,P均＜0.05),与HOMA-tR呈正相关(r=0.894、0.869,P均＜0.05).结论 间歇低氧暴露使大鼠肝细胞GLUT-2、GCK蛋白表达下调,可能参与间歇低氧条件下胰岛素抵抗的发生.     

间歇低氧对大鼠肝脏GSK-3及mTOR表达的影响

目的 测定间歇低氧大鼠肝脏糖原合成酶激酶-3(GSK-3)及哺乳动物雷帕霉素靶蛋白(mTOR)的表达,观察间歇低氧对胰岛素信号转导通路的影响.方法 将24只健康雄性Sprague-Dawley大鼠按照随机数字表法分成间歇空气组(NC组)、间歇低氧4周组(IH4组)、间歇低氧8周组(IH8组),每组8只.于上午9:00至下午5:00将IH4组及IH8组暴露于间歇低氧舱内,NC组则给予间歇压缩空气.检测各组大鼠空腹血糖、空腹胰岛素(FINS),并以稳态模型评估-胰岛素敏感指数(HOMA-IS)及稳态模型评估-胰岛素抵抗指数(HOMA-IR)评价胰岛素抵抗;免疫组化法测定大鼠肝脏GSK-3及mTOR的表达,以平均灰度值评价二者的蛋白表达量.结果 与NC组相比,IH4组、IH8组HOMA-IS降低,空腹血糖、FINS、HOMA-IR升高,以IH8组更为显著(F值分别为62.52,100.37,68.90,8549,P均＜0.01);与NC组相比,IH4组、IH8组GSK-3及mTOR蛋白表达均升高,以IH8组更明显(F值分别为72.25,148.01,P均＜0.01).Pearson相关分析显示GSK-3、mTOR平均灰度值与HOMA-IS呈正相关(r =0.786,0.811,P均＜0.01),与HOMA-IR呈负相关(r=-0.882,-0.889,P均＜0.01).结论 间歇低氧暴露使大鼠肝脏GSK-3、mTOR表达增加,从而引起胰岛素抵抗.     

慢性间歇低氧对大鼠肝细胞SOCS3表达的影响

目的通过构建慢性间歇低氧大鼠模型,检测模型大鼠空腹血糖、胰岛素水平及胰岛素抵抗指数并检测大鼠肝细胞SOCS3蛋白及其mRNA表达量的变化,探讨慢性间歇低氧对胰岛素抵抗的影响。方法选取健康雄性SD大鼠24只,按随机数字表法分为正常对照组（NC组）、慢性间歇低氧2周组（CIH2组）、慢性间歇低氧5周组（CIH5组）,每组8只。NC组无间歇低氧暴露,CIH2组、CIH5组暴露于间歇低氧环境中（每日8h,舱内最低氧浓度为6％～7％）。分别于第15天、第36天测定大鼠空腹血糖、放射免疫法测空腹胰岛素水平并按稳态模型评估法（HOMA）计算胰岛素抵抗指数,SABC法免疫组织化学试剂盒检测大鼠肝细胞SOCS3蛋白表达,以平均灰度值表示SOCS3蛋白表达量,荧光定量-PCR法检测SOCS3-mRNA基因表达量。结果与NC组比较,CIH2与CIH5组空腹血糖水平（差异有统计学意义,F=33．582,P〈0．05）、胰岛素水平（差异有统计学意义,F=35．633,P〈0．05）及HOMAIR（差异有统计学意义,F=49．045,P〈0．05）升高,且CIH5组最为显著（P〈0．05）;与NC组比较,CIH2与CIH5组SOCS3蛋白表达升高（差异有统计学意义,F-9．472,PG0．05）,CIH2与CIH5组差异无统计学意义（P〉0．05）;与NC组及CIH2组比较,CIH5组SOCS3-mRNA表达升高（差异有统计学意义,F=8．665,P〈0．05）,CIH2组升高不明显（差异无统计学意义,P〉0．05）。Pearson相关分析显示HOMA—IR与sOCS3平均灰度值呈负相关（r=-0．759,P〈0．001）,HOMA-IR与SOCS3-mRNA呈正相关（r=-0．603,P=0．01）。结论①CIH暴露使大鼠胰岛素水平及血糖水平升高且发生胰岛素抵抗,且随间歇低氧暴露时间延长,胰岛素抵抗程度加重。②CIH导致大鼠肝细胞内SOCS3蛋白表达增高,SOCS3-mRNA基因表达上调,CIH可能通过SOCS3参与了胰岛素抵抗的发生发展。     

间歇低氧对大鼠胰岛素抵抗及骨骼肌细胞GLUT4、Akt2的影响

目的 检测不同间歇低氧暴露时间对骨骼肌葡萄糖转运蛋白(GLUT)4与蛋白激酶B(PKB/Akt)2表达的影响,探讨二者在间歇低氧导致胰岛素抵抗中的作用.方法 选取健康雄性Sprague-Dawley大鼠40只,按照随机数字表法分为5组:常氧对照组(NC组),间歇低氧2周组(IH2组),间歇低氧4周组(IH4组),间歇低氧6周组(IH6组),间歇低氧8周组(IH8组),每组8只.IH2组、IH4组、IH6组、IH8组每天给予8h间歇低氧暴露(9:00～17:00),NC组室内环境正常饲养.检测各组空腹血糖和空腹胰岛素水平,计算稳态模型评估-胰岛素抵抗指数(HOMA-IR).采用免疫组织化学法检测大鼠骨骼肌GLUT4及Akt2蛋白的表达,蛋白表达量用平均灰度值表示,并分析GLUT4与Akt2的相关性.结果 与NC组相比,IH2组、IH4组、IH6组、IH8组空腹血糖、HOMA-IR升高,骨骼肌GLUT4与Akt2灰度值升高,并且随间歇低氧暴露时间的延长而升高明显(F =87.67～288.63,P均＜0.05);与NC组相比,IH2组、IH4组、IH6组、IH8组空腹胰岛素升高,其中IH2组、IH4组、IH6组,随间歇低氧暴露时间的延长而升高明显,IH8组较IH6组下降(F=86.04,P＜0.01).Pearson相关分析显示GLUT4与Akt2的表达呈正相关(r=0.895,P ＜0.05).结论 随着间歇低氧暴露时间的延长胰岛素抵抗程度增加,GLUT4与Akt2蛋白表达水平下降,二者在间歇低氧导致胰岛素抵抗的过程中起协同作用.     

高铝暴露致大鼠肌肉胰岛素抵抗作用及机制

目的观察高铝暴露对大鼠糖代谢、胰岛素抵抗水平及肌肉组织胰岛素受体底物(IRS)-1、葡萄糖转运蛋白(GLUT)-4表达的影响,探讨高铝暴露致大鼠胰岛素抵抗作用及部分机制。方法 SPF级Wistar大鼠60只大鼠随机分为高铝暴露组和对照组各30只,高铝暴露组予三氯化铝、对照组予生理盐水尾静脉注射,连续7 d,分别测定空腹血糖(FBG)、空腹胰岛素(FINS)水平,计算胰岛素抵抗指数(HOMA-IR)及胰岛素敏感指数(ISI),同时免疫组化法测定骨骼肌IRS-1、GLUT4表达。结果实验后,高铝暴露组较对照组FBG、FINS、HOMA-IR水平明显升高,ISI水平下降,肌肉组织IRS-1、GLUT-4表达显著下降(P0. 05或P0. 01)。结论高铝暴露可导致大鼠胰岛素抵抗、糖代谢异常发生,其机制可能与高铝暴露后IRS-1、GLUT-4表达下降有关。     

高脂饮食诱导的肥胖大鼠胰腺蛋白酪氨酸磷酸酶1B表达增高

目的观察高脂饮食诱导的肥胖大鼠胰腺中蛋白酪氨酸磷酸酶1B（PTP-1B）的表达。方法选取SD大鼠20只，随机分为正常对照组10只，给予常规饲料；肥胖模型组10只，给予高脂饲料，共喂养12周。测定大鼠空腹胰岛素、血糖、甘油三酯、总胆固醇，附睾脂肪垫重量；观察肝脏形态学改变；进行葡萄糖耐量试验和胰岛素释放试验；用免疫组化和蛋白印迹法检测大鼠胰腺组织中PTP-1B蛋白的表达。用免疫沉淀法检测胰岛素受体（IR）和胰岛素受体底物1（IRS-1）磷酸化程度。结果（1）肥胖组胰岛素敏感指数显著低于对照组（0．36±0．18 vs 0．91±0．28，P〈0．05）；（2）肥胖组大鼠葡萄糖耐量受损，葡萄糖刺激的胰岛素Ⅰ相分泌反应受损；（3）肥胖组大鼠胰腺中PTP-1B蛋白与对照组相比，含量增加86％（P〈0．01）。肥胖组胰腺中胰岛素诱导的IR和IRS-1磷酸化程度都降低。结论高脂饮食诱导的肥胖大鼠胰腺中PTP-1B蛋白表达量升高，从而使胰岛素诱导的IR和IRS-1磷酸化程度降低，可能是肥胖状态下引发胰岛产生胰岛素抵抗的机制之一。     

高脂饮食诱导肥胖大鼠胰腺中蛋白酪氨酸磷酸酶1B的表达和活性增高

目的：观察不同时间肥胖大鼠胰腺组织中蛋白酪氨酸磷酸酶1B（PTP-1B）的表达和活性变化，以及其底物蛋白IR和IRS-1经胰岛素刺激后磷酸化程度的变化，探讨肥胖大鼠胰岛胰岛素抵抗发生的可能机制。     

吡格列酮对高脂饮食诱导的胰岛素抵抗大鼠肝组织蛋白酪氨酸磷酸酶-1B及胰岛素受体底物-2表达的影响

目的 观察毗格列酮对高脂饮食诱导的IR大鼠肝组织蛋白酪氨酸磷酸酶-1B（PTP-1B）及胰岛素受体底物-2（IRS-2）表达的影响。方法40只SD大鼠随机分为高脂饮食（HF）组30只和正常对照（Nc）组10只,其中HF组又分为高脂对照（HFN）亚组和毗格列酮（HFP）亚组,每组各15只。喂养12周后,HFP亚组给予吡格列酮灌胃2周,并测定大鼠体重、FPG、Fins、TG、TC、IS。应用免疫组化、免疫印迹、免疫沉淀技术检测肝组织PTP-1B及IRS-2的表达。结果免疫组化：HFN亚组PTP-1B表达较NC组增高（P〈0．01）,HFP亚组较HFN亚组降低（P〈0．01）;免疫印迹：HFN、HFP亚组PTP-1B表达均高于NC组（P〈0．01或P〈0．05）,且HFP亚组低于HFN亚组（P〈0．01）;免疫沉淀：HFN亚组IRS-2磷酸化程度较NC组降低（P〈0．01）,HFP亚组较HFN亚组增高（P〈0．05）。结论吡格列酮能够改善IR,其作用机制可能与抑制PTP-1B表达,从而使胰岛素信号转导分子IRS-2表达增强有关。     

重组人胰岛素样生长因子1的促糖代谢作用研究

目的 研究胰岛素样生长因子１对糖代谢的影响。方法 分别以Ｂａｌｂ／ｃ ３Ｔ３成纤维细胞和昆明种小鼠为对象,研究重组人胰岛素样生长因子１的降糖作用。结果 （１）ＩＧＦ１使Ｂａｌｂ／ｃ３Ｔ３细胞培养液和葡萄糖浓度降到对照组的６５％,与胰岛素的降糖能力相似;（２）ＩＧＦ１能使小鼠血糖降到正常值２０％左右,降糖作用呈剂量－效应曲线。     

Determinants of daily insulin use in Type 1 diabetes

OBJECTIVE: Insulin need for a given degree of glucose control varies markedly among individuals. We examined which factors determine daily insulin use in patients with Type 1 diabetes. METHODS: A cross-sectional study was performed in 416 patients. Clinical parameters, medication use, physical activity, smoking, alcohol consumption, and laboratory parameters were determined. RESULTS: Body mass index and waist circumference were positively related to daily insulin use (2.3 U/kg/m(2), 95% CI=1.9-2.7 and 0.8 U/cm, 95% CI=0.6-0.9, adjusted for age and sex). Age, female sex, and duration of diabetes were inversely related to daily insulin dose. There was an increase of 3.6 U of insulin per mmol/l triglycerides (95% CI=1.04-6.2) and a decrease of 5.9 U of insulin per mmol/l high-density lipoprotein cholesterol (95% CI=-10.0 to -1.8), adjusted for age, sex, and weight. For blood pressure-lowering drugs, the strongest relation was found for thiazide diuretics (difference of 7.1 U insulin/day, 95% CI=0.2-14.2, adjusted for age, sex, and weight). The use of an insulin pump and physical activity were related to lower daily insulin need: -8.7 U/day (95% CI=-11.8 to -5.5) and -1.7 U/day per activity score unit (95% CI=-3.2 to -0.2), respectively, adjusted for age, sex, and weight. Smoking was related to an increased need of 5.3 U/day (95% CI=1.5-9.0), adjusted for age, sex, and weight. CONCLUSIONS: Our results show that components of the metabolic syndrome are positively related to daily insulin use. Also, decreased physical activity, smoking, and the use of blood pressure-lowering drugs, which influence insulin sensitivity, are associated with an increased insulin need. These findings suggest that the presence of insulin resistance in Type 1 diabetes or "double diabetes" plays a key role in determining daily insulin need.     

固醇调节元件结合蛋白1c对骨骼肌细胞胰岛素受体底物1表达调控的影响

目的 探讨固醇调节元件结合蛋白1c（SREBP-1c）对大鼠骨骼肌细胞胰岛素受体底物1（IRS-1）表达调控的影响.方法 采用酶联合消化法取2～3 d SPF级雄性SD大鼠原代骨骼肌细胞,将原代细胞分为对照组（C）、对照＋胰岛素组（C＋I）、高脂组（PA）及高脂＋胰岛素组（PA＋I）.将表达SREBP-1c腺病毒转染L6细胞,根据感染复数（MOI）分为含绿色荧光蛋白阴性载体（GFP）组、MOI值为5、50、100、200组.将靶基因为SREBP-1c的干扰RNA （siRNA）转染L6细胞,并分为空白对照组、阴性siRNA组及SREBP-1c siRNA组.Western blotting和实时定量聚合酶链反应（RT-PCR）检测SREBP-1c、IRS-1、蛋白激酶B（Akt）基因及蛋白表达,油红O染色法检测细胞内脂质沉积情况.多组资料比较采用方差分析,两两比较采用最小显著差异法.结果 与C组相比,PA组SREBP-1c基因和蛋白水平升高（分别为2.72±0.08比1.00±0.18,3.02 ±0.19比1.00±0.05,t=15.240、18.289,均P＜0.05）,IRS-1基因和蛋白水平降低（分别为0.71 ±0.04比1.00 ±0.05,0.82 ±0.04比1.00±0.04,t=-7.960、-6.052,均P＜0.05）,丝氨酸磷酸化IRS-1蛋白表达升高,丝氨酸磷酸化Akt（p-Akt）蛋白表达下降（t=20.987、-5.869,均P＜0.05）.与GFP组相比,MOI值为50、100和200组的SREBP-1c基因和蛋白表达呈剂量依赖性上升（均P＜0.05）,IRS-1基因和蛋白表达水平呈剂量依赖性下降（均P＜0.05）.与空白对照组和阴性siRNA组相比,SREBP-1c siRNA组SREBP-1c基因和蛋白水平降低,IRS-1蛋白表达升高（均P＜0.05）.结论 SREBP-1c可抑制骨骼肌IRS-1胰岛素信号通路,参与肌细胞胰岛素抵抗的发生.     

Symptomatic hypoglycaemia in 411 type 1 diabetic patients

The frequency of symptomatic hypoglycaemic episodes was studied in 411 randomly selected conventionally treated Type 1 diabetic out-patients. Between two consecutive visits to the out-patient clinic each patient filled in a questionnaire at home. The number of hypoglycaemic episodes was then recorded prospectively in a diary for 1 week. From the questionnaires, the (retrospective) frequencies of mild and severe symptomatic hypoglycaemia were 1.6 and 0.029 episodes patient-1 week-1. From the diaries, the (prospective) frequencies of mild and severe hypoglycaemic episodes were 1.8 and 0.027 patient-1 week-1. Symptomatic hypoglycaemia was more frequent on working days than during weekends (1.8:1) and more frequent in the morning than during the afternoon, evening, and night (4.5:2.2:1.4:1). The symptoms of hypoglycaemia were non-specific, heterogeneous, and weakened with increasing duration of diabetes. During their diabetic life, 36% of the patients had experienced hypoglycaemic coma. The frequency of hypoglycaemia was positively, but only weakly, correlated with insulin dose, number of injections, percentage unmodified insulin of the total dose, and HbA1c (mild hypoglycaemia only). The frequency was also negatively, but weakly, correlated with age and HbA1c (episodes with coma only), but not correlated with sex, duration of diabetes, or patients' ratings of worries about mild and severe hypoglycaemia.     

甲状旁腺素受体1表达对高糖状态下INS-1细胞功能影响研究

目的 观察甲状旁腺受体1(PTH1R)的表达对胰岛β细胞胰岛素合成与分泌功能影响.方法 构建出PTH1R基因沉默的细胞模型后,分别应用放射免疫法观察25 mmol/L D-葡萄糖处理后对照组、阴性基因克隆组(siPTH1R-NC)、PTHrP组及阳性基因序列组(siPTH1R)细胞内胰岛素含量、葡萄糖刺激胰岛素分泌能力、应用Fluo-3/AM 检测INS-1细胞内钙离子浓度及应用INS-1细胞2-脱氧-[3H]-葡萄糖摄入率检测INS-1细胞葡萄糖转运能力.结果 PTHrP组胰岛素分泌能力高于其他3组,siPTH1R组则低于对照组及siPTH1R-NC组(均P＜0.01);PTHrP组中细胞内胰岛素含量显著高于对照组、siPTH1R-NC及siPTH1R组(均P＜0.01),其他3组间差异无统计学意义;PTHrP组中钙离子浓度水平高于其他3组,siPTH1R组低于对照组及siPTH1R-NC组.PTHrP组中细胞2-脱氧-[3H]-葡萄糖摄入率高于其他3组.结论 高糖状态下PTH1R表达水平与INS-1细胞胰岛素合成与分泌功能有关,可能为INS-1细胞自我保护的一种作用.

Abstract：

Objective To observe insulin synthesis and secretion in INS-1 under high glucose, and to clarify the effect of PTH1R. Methods After successful construction of recombinant PTH1R-siRNA vectors in INS-1 cell, insulin secretion and intracellular insulin content of control group, siPTH1R-Negative control group, PTHrP group, and siPTH1R group under 25 mmol/L glucose were measured by radioimmunoassay in INS-1 cell. Intracellular calcium were detected by Fluo-3/AM and the capability of glucose transport was calculated by assaying the uptake of [3H]-2-deoxy-D-glucose in cells.Results Compared with control group, and siPTH1R-NC group, PTHrP group showed increased capability of insulin secretion; PTHrP group had higher intracellular insulin levels than others; PTHrP group showed increased intracellular calcium; the uptake of [3H]-2-deoxy-D-glucose under high glucose after 48h of PTHrP group was increased(all P＜0.01). Conclusion There is a close relationship between PTH1R activation and insulin secretion and synthesis, PTH1R activation may be one of the protective mechanisms in maintaining function of β-cell under high glucose.     

多种胰岛素过敏的1型糖尿病患者脱敏一例及文献复习

目的报告对多种胰岛素过敏的1型糖尿病患者脱敏随访治疗情况，并复习国内外报道的相关资料，以提高对该病的诊治认识。方法对该患者用过小剂量序贯皮下注射胰岛素、胰岛素泵持续泵入胰岛素（诺和灵R、猪胰岛素）、地塞米松加入胰岛素泵诺和灵R中持续泵人等方法进行胰岛素脱敏治疗。监测指标为患者胰岛素注射部位的红斑、硬结直径及瘙痒程度以及胰岛素抗体水平。结果胰岛素泵治疗时，过敏反应较前明显减轻，尤其是方波输注模式时瘙痒明显减少。使用诺和灵R＋地塞米松胰岛素泵治疗时最少发生过敏反应，表现为注射部位无红斑，无硬结或偶有直径0．5cm的硬结，不伴瘙痒；胰岛素泵治疗结束3个月，胰岛素笔注射后，皮肤过敏反应逐渐减轻至消失，无红斑和瘙痒，大腿部位有时有小硬结，胰岛素抗体逐渐降低至正常，但出现右侧腹部局部脂肪萎缩。结论地塞米松与胰岛素混合加入胰岛素泵的方法胰岛素过敏反应最轻微，胰岛素泵方波输注模式有助减轻胰岛素过敏症状。     

Relationship Between Insulin Sensitivity and Insulin Receptor Substrate-1 Mutations in Non-diabetic Relatives of NIDDM Families

Insulin receptor substrate-1 (IRS-1) occupies a key position in the insulin-signalling pathway. Two mutations of the IRS-1 gene (Gly₉₇₂Arg and Ala₅₁₃Pro) have been described, although their roles in the development of insulin resistance and non-insulin-dependent diabetes mellitus (NIDDM) remain controversial. Insulin resistance has been described in non-diabetic relatives of NIDDM families, suggesting that it may be due to an inherited defect of insulin action. We therefore examined the relationships between the two mutations and insulin senstivity in 93 non-diabetic first degree relatives from North European families with 2 or more living NIDDM subjects. Anthropometric measurements, an oral glucose tolerance test, and an insulin tolerance test to assess insulin sensitivity (K_ITT) were performed. Basal insulin sensitivity was assessed by homeostasis model assessment (HOMA). Comparisons were made between the following relative subgroups: with (n = 9) and without (n = 84) the 972 mutation; with (n = 5) and without (n = 88) the 513 mutation; and with either one or both mutations (n = 13) or without either (n = 80). General linear model analysis was used to compare K_ITT and HOMA between the subgroups with the anthropometric variables known to influence insulin sensitivity as covariates. There were no significant differences between the subgroups for K_ITT and HOMA. In conclusion, the 513 and 972 mutations, alone and in combination, are not associated with decreased insulin sensitivity in non-diabetic relatives of NIDDM families.     

Insulin increases plasma somatomedin C (IGF-1) concentrations in adult type 1 diabetic patients

The role of insulin in the control of somatomedin release has been investigated in people with Type 1 diabetes. Six patients underwent insulin-induced hypoglycaemia of 20 min duration and 8 patients were studied using the hyperinsulinaemic euglycaemic clamp technique at insulin infusion rates of 0.25, 1.25, 2.5, and 0.25 mU kg-1 min-1 for 1 h at each rate. In the first study plasma insulin concentrations rose from (median, range) 23 (10-36) to 114(60-200) mU l-1 at the onset of hypoglycaemia, and fell to 53 (23-100) mU l-1 after 20 min hypoglycaemia and 30 (15-73) mU l-1 on return to normoglycaemia. Plasma IGF-1 rose from 140 (96-292) to 179 (127-352) micrograms l-1 (p less than 0.05) at the onset of hypoglycaemia and fell to 131 (125-173) micrograms l-1 after 20 min and to 154 (121-287) micrograms l-1 at the end of the study. During hyperinsulinaemia plasma insulin rose from 23 (19-40) mU l-1 at the lowest infusion rate to 61 (33-84) and 148 (68-200) mU l-1 at the two higher infusion rates. Over the same period, plasma IGF-1 increased from 91 (13-203) to 123 (98-182) micrograms l-1 (p less than 0.05) and 109 (84-160) micrograms l-1. There was no correlation between growth hormone levels and IGF-1 in either study. These results suggest that insulin produces short-term increases in IGF-1 levels in man in the absence of a growth hormone response.     

Human Insulin Receptor Substrate-1: Variant Sequences in Familial Non-insulin-dependent Diabetes Mellitus

The aetiology of NIDDM is uncertain, although family and twin studies indicate an important role for genetic factors in disease onset. The function and position of IRS-1 within the insulin signalling pathway make it a prime candidate gene for the development of insulin resistance and NIDDM. Insulin resistant families were identified by studying unaffected first degree relatives from families with 2 or more living NIDDM subjects. Insulin sensitivity was determined in the relatives using the insulin tolerance test, and 15 families were identified as insulin resistant. One NIDDM subject from the 10 most resistant families was selected and the entire coding region of IRS-1 analysed by SSCP analysis. Four normoglycaemic subjects with no family history of diabetes served as controls. Five variant sequences of IRS-1 were identified within the NIDDM subjects; 2 silent polymorphisms at codons 235 (GGG to GGA) and 893 (CCG to CCC): 2 non-conservative mutations (Ala₅₁₃Pro; Gly₉₇₂Arg) and a codon deletion (Ser_681-7 to Ser_681-6). The influence of the non-conservative mutations alone, and in combination with other abnormalities of the insulin signalling pathway on peripheral insulin action, remains to be determined.