妊娠期糖尿病的发病机制

妊娠期糖尿病(GDM)为糖尿病的一种特殊类型,对母亲和胎儿都有不利影响。GDM孕妇存在比正常孕妇更强烈的胰岛素抵抗,并且胰岛β细胞功能存在缺陷。C反应蛋白、白细胞介素6等炎性因子参与了GDM孕妇慢性炎症的发生。免疫失衡造成细胞毒性因子的释放增加,增加了GDM发生的风险。人类白细胞抗原分子作为免疫调节分子,可能与GDM有一定的关系,GDM孕妇某些人类白细胞抗原基因型频率是增加的。     

抵抗素研究的新进展

抵抗素是一种由脂肪细胞和巨噬细胞分泌的多肽类激素,起初作为肥胖和胰岛素抵抗或糖尿病间的关联物质被提出,最新证据提示抵抗素是一种前炎性细胞因子。过去几年,通过对抵抗素在肥胖、胰岛素抵抗、代谢和心血管等相关并发症模型中的结构、表达、分泌、调节和循环水平的分析,试图解释抵抗素在啮齿类动物和人体中的生理功能。本文综述了目前对抵抗素在这些条件下研究的最新进展。     

脉泰颗粒择时给药对胰岛素抵抗高脂模型家兔的影响

目的:观察脉泰颗粒择时给药对胰岛素抵抗(IR)高脂模型家兔的影响。方法:用高脂高糖饲料喂养家兔诱导产生IR,对造模后有关指标进行分析。结果:模型组与正常组比较,TG、TC、LDL-C、ApoB明显升高(P<0.01),ApoAI显著降低(P<0.01),HDL-C无明显变化。中药组与模型组比较,TG、TC、LDL-C、ApoB明显减少(P<0.01),ApoAI、HDL-C明显增加(P<0.01)。结论:高脂高糖饮食可造成家兔脂代谢紊乱,脉泰颗粒可有效调节血脂,减轻胰岛素抵抗,防止动脉粥样硬化形成,预防心脑血管疾病发生。     

高血压病患者胰岛素抵抗与其他代谢异常的关系

目的探讨高血压病患者胰岛素敏感性与其他代谢异常的关系。方法用正常血糖胰岛素钳夹技术测定26例健康者和84例高血压病患者的葡萄糖代谢率，用盐负荷升压及减钠降压试验测定盐敏感性。结果高血压病患者葡萄糖代谢率比正常人明显降低（P〈0．01），84例高血压病患者中有47例（55.9％）存在胰岛素敏感性降低，50例（59.5％）存在盐敏感。按葡萄糖代谢率数值把84例高血压病患者分为两组：高血压病合并胰岛素敏感性降低组（降低组）47例，胰岛素敏感性正常组（正常组）37例。经方差分析，纠正体重指数后，降低组的各项代谢指标仍比正常组高，盐敏感发生率分别为58．1％，21．7％（P〈0．01）。结论胰岛素敏感性降低加重了高血压病患者盐、血脂及血尿酸等的代谢紊乱，胰岛素抵抗可能是其他各项代谢异常的根源。     

参芪复方对GK大鼠早期动脉硬化胰岛素抵抗的影响

目的:观察参芪复方对GK大鼠2型糖尿病早期动脉硬化胰岛素抵抗的影响.方法:SPF级GK大鼠(自发性糖尿病大鼠)44只及Wistar大鼠11只按血糖水平随机分为正常对照组、模型组、雷米普利组、参芪复方低剂量组、参芪复方高剂量组.4组GK大鼠组造模:10 mg·kg-1·d-1腹腔注射N-硝基-L-精氨酸甲酯(L-NAME),同时给高脂饮食,连续14 d造模.正常对照组给生理盐水.2周后开始给药,各组分别给相应受试药物28 d.用放免法测IL-6、INS,计算IAI、IRI,光镜下观察胸主动脉内膜病变的数目和程度.结果:参芪复方高、低剂量组的血清IL-6、INS含量较模型组下降,IRI明显降低(P＜0.01),IAI明显升高,胸主动脉内膜病变数目与程度均有明显减少(P＜0.01).结论:以益气养阴、清热生津、活血化瘀为治则的参芪复方能明显下调GK大鼠内皮细胞损伤的周围血的IL-6及INS的表达,降低IRI,升高IAI,减少胸主动脉内膜病变的数目和程度,在一定程度上保护了胰岛庀赴墓δ芎脱a管内皮细胞,防止动脉粥样硬化的发生和发展.     

妊娠不同时期低蛋白饮食对子代大鼠激素抵抗的影响

目的 探讨低蛋白对大鼠出生体重影响的关键时间、成年后是否出现多种激素抵抗以及各自的特点。方法 妊娠鼠随机分为五组（每组12只）：正常对照组、妊娠早期低蛋白组、妊娠中期低蛋白组、妊娠晚期低蛋白组以及全程低蛋白组，足月自然分娩后观察新生鼠体重及数目。再以各组小于孕龄（small for gestational age，SGA）鼠为研究对象（每组9只），于生后12周时测体重（body weight，BW），双侧肾周脂重（fat weight，FW），计算FW／BW；并采用ELISA法测定血糖、胰岛素及瘦素，计算胰岛素敏感指数（insulin sentivity index，ISI）。结果 早期低蛋白饮食组所分娩的新生鼠平均体重（8．72±0．51）g，与正常对照组（7．10±0．62）g比较显著升高（P〈0．05）；全程低蛋白饮食组所分娩的新生鼠数目明显减少，且体重（4．87±0．3）g明显低于正常对照组（P均〈0．01）。晚期低蛋白组大鼠生后12周时体重（6．79±0．56）g升高但无统计学意义（P〉0．05），但胰岛素、瘦素[分别为（4．96±2．11）μg／L和（6．36±0．68）μg／L]升高及ISI（4．29±0．18）水平明显降低（P〈0．05），而全程低蛋白组鼠体重（223．64±17．91）g、肾周脂重（2．36±1．51）g及FW／BW（11．03士6．17）‰、胰岛素、瘦素水平升高[分别为（5．43±1．32）μg／L、（8．07±0．91）μg／L]，而ISI（3．91±0．42）低于对照组（P〈0．05或〈0．01）。结论 妊娠早期低蛋白可能导致出生体重的增加，全程低蛋白导致低出生体重；妊娠晚期的低蛋白及全程低蛋白引起的低出生体重鼠在成年后更容易发生胰岛素及瘦素的抵抗。     

4-Hydroxyisoleucine: effects of synthetic and natural analogues on insulin secretion

4-Hydroxyisoleucine, a peculiar amino acid extracted from fenugreek seeds and never found in mammalian tissues, exhibits interesting insulinotropic activity. To investigate the structural requirements for this stimulating effect, the insulinotropic activity of the major isomer (2S,3R,4S) of 4-hydroxyisoleucine, in the presence of 8.3 mM glucose, was compared to that of (1) its minor isomer (2R,3R,4S) (2) its lactone form, (3) classical structurally related amino acids, and (4) synthetic monomethylated analogues. In the isolated, ex vivo, perfused rat pancreas, only the major isomer of 4-hydroxyisoleucine (200 μM) potentiated insulin release. On incubated isolated rat islets, the threshold concentration for a significant increase (P<0.05) in insulin release was 200 μM for (2S,3R,4S) 4-hydroxyisoleucine, 500 μM for (2S,4R) and (2S,4S) γ-hydroxynorvalines as well as (2S,3S) and (2S,3R) γ-hydroxyvalines, and 1 mM or more for other congeners. In conclusion, the insulinotropic properties of 4-hydroxyisoleucine, in the micromolar range, are seen only in the presence of the linear major isoform; they also require carbon in S-configuration, full methylation and carbon γ-hydroxylation.     

Pharmacodynamics and pharmacokinetics of intravenous glibenclamide in Caucasian and Chinese patients with type-2 diabetes

Objective: We analysed the kinetics and effects of glibenclamide (Gb) on glucose, insulin and proinsulin secretion in two ethnic groups (10 in each) of type-2 diabetic patients, one of Caucasian, the other of Chinese origin. Background: Diabetes mellitus type 2 is a global disease affecting all ethnic groups. There are ethnic differences in both the prevalence and metabolic characteristics of the disease. Important interethnic pharmacodynamic and pharmacokinetic differences have been reported for several drugs. With few exceptions, detailed studies on sulphonylurea are lacking. Material and methods: The patients were studied on two occasions when either no Gb (control) or 1.25 mg Gb was administered i.v., immediately before the administration of a 75-g oral glucose tolerance test. Concentrations of insulin and proinsulin were determined by means of radioimmunoassay without cross-reactivities. Gb concentration was determined using high-performance liquid chromatography. Pharmacodynamic results were calculated using net areas under the curves, with basal values set as zero. A P value less than 0.05 was considered significant. Results: When glucose was administered orally without Gb, Chinese patients had higher plasma glucose increases at 10 min (7.6 mmol/l × min vs 2.6 mmol/l × min) and higher increases of plasma insulin levels than Caucasians at both 10 min (198 pmol/l × min vs 54 pmol/l × min) and 30 min (2286 pmol/l × min vs 1198 pmol/l × min). When Gb was administered, the plasma glucose increases were reduced, and the increases of serum insulin and proinsulin levels were greater in both ethnic groups. Compared with the basal values (−1 min), proinsulin/insulin ratios (RPI) were lowest at 10–30 min, followed by an increase. Chinese patients had higher increases of serum insulin levels at 10 min (1109 pmol/l × min vs 550 pmol/l × min) and a lower RPI at 30 min (6.0% vs 7.6%) and 240 min (15.0% vs 21.0%) relative to Caucasians. Serum Gb data were best fitted to a biexponential i.v. model. There were no interethnic differences in any of the pharmacokinetic parameters. Conclusion: In summary, following oral glucose administration without Gb, Chinese type-2 diabetic patients had higher plasma insulin levels but also higher plasma glucose levels during the first 10 min, which might reflect reduced insulin sensitivity or more rapid glucose absorption. Gb augmented glucose-induced release of both insulin and proinsulin in both ethnic groups; the effect on insulin secretion was more pronounced. In conclusion, minor pharmacodynamic but no pharmacokinetic differences were found between the two groups. It seems appropriate to employ the same dosage principles when using Gb in Caucasians and Chinese. Received: 15 June 1999 / Accepted in revised form: 9 August 1999     

胰岛素昏迷治疗精神分裂症致精神衰退100例

目的：研究影响精神衰退的相关因素。方法：对曾用正规胰岛素昏迷疗法治疗的１００例精神分裂症患者的临床疗效进行评估,并设对照组进行对比分析研究。结果：精神病的精神衰退与胰岛素昏迷疗法相关。临床资料,胰岛素昏迷治疗衰退比例８６．０％,服用抗精神病药物治疗的衰退比例为１２．０％,经ｔ检验差异极显著（Ｐ〈０．０１）。结论：胰岛素昏迷治疗加速加重精神分裂症的精神衰退,对照组中单纯型、青春型患者由于未能长期服药     

Insulin secretion in children with growth retardation

The effect of tolbutamide administration on insulin secretion was studied in 69 children with growth retardation. Diminished insulin secretion was found in all the patients, compared to the control group. This insulin deficit was most evident in patients with isolated, total GH deficiency and least evident in children with idiopathic short stature. Intermediate values were found in dwarfism due to isolated, partial GH deficiency.These results favour the hypothesis that hypoinsulinism contributes to the somatotropin deficiency in causing growth retardation.Abbreviations PD pituitary dwarfism - FSS familial short stature - GR growth retardation - GH growth hormone - ISS idiopathic short stature - tbt tolbutamide - GHtd isolated, total GH deficiency - GHpd isolated, partial GH deficiency