Unaltered insulin sensitivity during calcium channel blockade with amlodipine

Summary The sensitivity of peripheral tissues to insulin is of pathophysiological, therapeutic and possibly also of prognostic relevance. Calcium channel blockers are widely used in the treatment of cardiovascular disorders that are commonly associated with decreased insulin sensitivity (S_I). To evaluate the effects of calcium channel blokkade on S_I, glucose homoeostasis and lipid profiles, studies were made of S_I (determined by the Minimal Model Method of Bergman), basal glucose and insulin levels, serum total triglyceride (Tg) and lipoprotein cholesterol (C) fractions and certain other variables in 38 healthy young men (24 y) during placebo and after 3 weeks of calcium channel blockade with amlodipine 5 mg once daily. Measurements were made after 3 days on a standard diet (2200 kcal · day^–1, 45% carbohydrates, 40% fat and 15% proteins) and after an overnight fast. Compared to placebo, amlodipine decreased supine systolic blood pressure (P<0.01). Heart rate, body weight and 24 h urinary sodium excretion were unaltered, and so were fasting plasma glucose (placebo vs amlodipine: 4.86 vs 4.83 mmol·1^–1, respectively) and insulin levels (7.7 vs 7.9 U·ml^–1), S_I (10.5 vs 9.6·10^–4 × min^–1 pro U·ml^–1), serum total Tg, C and lipoprotein C fractions.The findings demonstrate unchanged insulin sensitivity and secretion, as well as lipoprotein regulation, during maintenance administration of 5 mg amlodipine daily to healthy young men.This work was supported in part by the Swiss National Science Foundation     

Devices for the treatment of diabetes: today

Although single or multiple daily subcutaneous injections of insulin with syringes are the mainstay of insulin delivery techniques for the treatment of diabetes mellitus, several other methods are now available. The present paper will review the main problems occurring with the classical subcutaneous insulin therapy and the possible solutions given by the use of new devices, including more particularly insulin jet injectors, pens, and portable pumps. This review has to be considered as an introduction to the presentations of this symposium devoted to implantable pumps, glucose sensors, and artificial pancreas, respectively.     

转化生长因子-β1和胰岛素对人鼻中隔软骨细胞增殖和分化影响的研究

目的 了解转化生长因子-β1(transforminggrowth factor-beta 1,TGF-β1)和胰岛素对人鼻中隔软骨细胞增殖和分化的影响。方法 体外培养人鼻中隔软骨细胞,采用四甲基偶氮唑蓝(MTT)代谢和35S-Na2SO4掺入的检测比较不同浓度TGF-β1和胰岛素对人鼻中隔软骨细胞的增殖以及软骨基质蛋白多糖合成的影响,观察TGF-β1和胰岛素对软骨细胞表型的影响。结果在15％血清的培养条件下,TGF-β1和胰岛素均能显著促进软骨细胞增殖,且在各自一定的浓度范围内呈量效关系,联合作用效果累加;TGF-β1、TGF-β1和胰岛素联合作用促使软骨基质蛋白多糖的合成量明显提高;TGF-β1使传代软骨细胞去分化提前。结论一定浓度的TGF-β1、胰岛素和TGF-β1 胰岛素对体外培养的人鼻中隔软骨细胞具有显著的促增殖作用。     

2001年—2003年第1季度北京地区门诊患者降血糖用药动态分析

目的 :了解北京地区糖尿病患者的用药需求 ,并对降血糖药物进行分析。方法 :采用《医院处方分析》课题 (北京地区 )2 0 0 1年～ 2 0 0 3年每年第 1季度门诊降血糖用药的处方数据进行比较。结果与结论 :通过统计 ,北京地区糖尿病患者人数不断增多 ,且人们更多选用了新型降糖药。在临床应用中 ,口服制剂以磺酰脲类用量居主导地位 ,而α-葡萄糖苷酶抑制剂用量逐年上升 ;使用基因合成人胰岛素较动物胰岛素的用量逐年增多 ,为控制糖尿病用药及合理应用提供了依据     

Postprandial glycaemia after regular and lispro insulin in children and adolescents with diabetes

We compared the postprandial blood glucose (BG)-levels following preprandial regular insulin or lispro insulin before and after eating in adolescents with diabetes. Lispro is a rapidly absorbed insulin analogue. Lispro insulin injected immediately before breakfast reduced the postprandial BG-rise significantly compared to the 20 min preprandially administered regular insulin (P<0.01). Postprandial lispro injection resulted in similar BG values as the standard treatment with regular insulin 20 min preprandially. Conclusion Lispro insulin injected immediately before the meal leads to lower postprandial BG levels and seems to be an option for teenagers who use multiple preprandial insulin injections. Postprandial lispro administration could be a benefit in certain situations since it resulted in similar BG values to preprandial regular insulin. Received: 13 March 1997 / Accepted: 26 May 1997     

Familial hyperproinsulinaemia due to a mutation substituting histidine for arginine at position 65 in proinsulin: identification of the mutation by restriction enzyme mapping

Familial hyperproinsulinaemia is a rare genetic disorder characterized by point mutations in the insulin gene which impair the conversion of proinsulin to insulin. We report here three members of a two-generation Caucasian family in whom this syndrome was identified by unexplained hyperinsulinism associated with normal glucose tolerance and normal insulin sensitivity. Plasma insulin immunoreactivity showed a reduced affinity for the insulin receptor and eluted mainly, on Biogel chromatography, at the position of proinsulin. Analysis of the PCR-amplified insulin gene by restriction enzyme mapping revealed a new recognition site for the enzyme Nla III, indicating a Arg⁶⁵ to His mutation. Sequence analysis of exon 3 confirmed this mutation in one allele of the gene. Conclusion This study reports a two-generation European-Caucasian family with hyperproinsulinaemia due to a substitution of His for Arg at position 65 in proinsulin, the seventh now identified worldwide and the second from Europe. The mutation generated a new restriction site on the insulin gene suggesting the usefulness of restriction enzyme mapping as a screening procedure. Received: 27 June 1997 / Accepted in revised form: 28 November 1997     

2型糖尿病糖耐量实验与胰岛素释放实验关系的探讨

目的 探讨2型糖尿病血糖与胰岛素释放的关系,以及血糖水平对血糖刺激的胰岛素释放的影响.方法 对50例2型糖尿病患者停用口服药24 h后,口服75 g葡萄糖行葡萄糖耐量实验(OGTT)及胰岛素释放实验(IRT).血糖采用cobas Integra 400 plus全自动生化分析仪测定,胰岛素采用美国Becoman Coulter Access2化学发光仪测定.结果 50例2型糖尿病患者按血糖水平与胰岛素释放的变化方向可分为4组:①A组:血糖水平与胰岛素水平曲线平行,均于1 h达峰值16例.②B组:胰岛素水平峰值延迟9例.③C组:血糖水平与胰岛素水平均于2 h达峰值,峰值延迟19例.④D组:血糖峰值延迟6例.结论 血糖水平与血清胰岛素水平呈负相关,但由于胰岛B细胞的个体差异很大,可以出现不同的分离现象,体现了糖尿病发病的异质性或个体差异性.     

50例妊娠合并糖尿病孕妇的妊娠期管理分析

目的 :探讨妊娠合并糖尿病孕妇的妊娠期管理方法。方法 :将 5 0例妊娠合并糖尿病孕妇与 4 8例正常孕妇比较。结果 :5 0例妊娠期糖尿病孕妇中有 38例 ( 76 % )经饮食疗法后血糖控制效果良好 ,另 12例需饮食疗法加胰岛素治疗方能将血糖控制在正常范围内。经临床治疗后 ,5 0例妊娠合并糖尿病的孕妇 ,除早产发病率高于非糖尿病组孕妇外(P <0 0 5 ) ,妊高征、感染、产后出血、羊水过多、羊水过少、胎儿窘迫、巨大儿、胎儿生长受限 (FGR)、新生儿窒息、新生儿高胆红素血症等发病率与非糖尿病组孕妇无区别。结论 :加强妊娠合并糖尿病孕妇的妊娠期管理 ,用饮食疗法或胰岛素治疗控制血糖 ,适时终止妊娠 ,可有效降低母婴并发症的发生     

A natural lipopeptide of surfactin for oral delivery of insulin

Abstract

Surfactin, a natural lipopeptide produced by Bacillus, is gaining attention for potentially biomedical and pharmaceutical applications. Here, surfactin was assayed for oral delivery of insulin (INS) by its ability to bind to and promote protein to penetrate through the cell membrane. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, surfactin was found to form co-precipitates with INS to protect it from acidic and enzymatic attack in the gastrointestinal tract. Further analysis by non-reductive electrophoresis showed surfactin could bind to INS forming heteropolymers. Analysis with circular dichroism, we found this binding significantly influenced the INS structure with decreased rigid α-helix and β-turn, but with increased flexible β-sheet and random coil. The change with more flexible structure was favorable for INS to penetrate through the cell membrane. Fluorescence spectra analysis also showed surfactin could lead Phe and Tyr in the inner of INS exposed outside, further promoting INS permeabilization by improving the hydrophobic-lipophilic interactions between INS and cell membrane. As a result, the effective permeability (Peff) of INS plus surfactin was 4.3 times of that of INS alone. In vivo assay showed oral INS with surfactin displayed excellent hypoglycemic effects with a relative bioavailability of 12.48% and 5.97% in diabetic mice and non-diabetic dogs, respectively. Summary, surfactin is potential for oral delivery of INS by its role as an effective protease inhibitor and permeability enhancer.     

雷公藤多甙对成人隐匿性自身免疫性糖尿病患者谷氨酸脱羧酶抗体和B细胞功能的影响

目的探讨雷公藤多甙（GTT）对成人隐匿性自身免疫性糖尿病（LADA）患者谷氨酸脱羧酶抗体（GAD-Ab）和B细胞功能的影响。方法60例LADA患者随机分为GTT组和对照组，应用GTT观察3个月前后空腹C肽、GAD-Ab和胰岛素抗体（IAA）的变化。结果①GTT组患者应用GTT治疗3个月后GAD-Ab阳性率下降，转阴率为43％，与对照组比较差异有显著性（P〈0．01）。②IAA治疗前后，2组组内和组间比较差异均无显著性。③GTT组患者治疗后C肽水平略有上升，组内治疗前后比较差异无显著性，而与对照组比较差异有显著性（P〈0．05）。结论研究提示GTT对GAD-Ab具有免疫抑制作用，并有一定的改善B细胞功能的趋势。