口服胰岛素研究进展

胰岛素 (Insulin)是治疗糖尿病的一个重要药物 ,尤其是治疗 1型糖尿病的必备药物。有学者在 1 997年报道 ,胰岛素的给药方式最主要的是通过皮下注射途径 ,另外大约有 1万到 2万病人是通过胰岛素泵途径 [1 ] 。上述传统的胰岛素给药方法与正常的药代动力学过程不同 ,经皮下和静脉注射后先经毛细血管、静脉系统回心脏 ,再经动脉系统到肝脏代谢及全身各效应细胞发挥作用 ,使胰岛素在外周血管滞留较长 ,不能模仿生理性胰岛素分泌。而体内胰岛素从胰岛 β细胞分泌后经门脉系统到肝脏代谢 ,经下腔静脉回心脏 ,再经动脉系统到全身各效应细胞发挥作…     

胰岛素给药途径的研究进展

近年来，随着DNA重组技术的发展及人工胰岛素(INS)的合成成功，INS正由单一的注射剂向非注射给药和可调式给药方向发展。现将INS给药途径的进展作一综述。     

走近口服胰岛素

诺和诺德公司最近已经开始进行胰岛素药片的Ⅰ期试验,如果试验成功,将会帮助糖尿病患者摆脱每日注射胰岛素的命运。诺和诺德公司已经招募了80名德国受试者,初步结果预计在2011年上半年即可获得。     

纳米粒体内靶向性的研究进展

纳米粒（Nanoparticle）一般指由天然或合成的高分子材料制成的、粒度为纳米级的（1～1000nm）固态胶体微粒。靶向给药指运用载体将药物选择性地浓集定位于靶器官、靶组织或靶细胞,使其药物浓度高于其他正常组织。纳米粒的体内靶向性一般分为被动靶向性和主动靶向性。被动靶向性是利用纳米粒的大小、质量、表面疏水性、静电作用、磁力作用等物理因素实现靶向给药。主动靶向性是指对纳米粒进行表面修饰,如在其表面耦联特异性的靶向分子（特异性的配体、单克隆抗体等）,通过靶向分子与细胞表面特异性受体结合,实现主动靶向治疗。自20世纪90年代以来．纳米粒作为靶向给药的载体一直是药物制剂研究的热点之一。现将纳米粒在肝脏、脑、骨髓和肿瘤中的药物靶向性研究进展综述如下。     

口服型胰岛素微囊研制的初步报告

目的 观察改变了材料分子量、微囊粒径的的聚丙交酯胰岛素微囊（ＰＬＡ－ＭＣＩ）体外释药及大鼠口服后血糖的变化。方法 体外释药在磷酸盐缓冲液（ＰＢＳ）中进行,胰岛素测定用福林－酚法。体内实验由糖尿病大鼠口服ＰＬＡ－ＭＣＩ后每小时血糖测定反映,并与口服纯胰岛素的二组对照及同期饥饿对照组血糖进行比较。结果 ＰＬＡ－ＭＣＩ在ＰＢＳ中３～７小时内释放了５１．０％～７３．４％的胰岛素,１１小时后释放达稳态。口服     

介绍婴幼儿口服给药的方法

由于各种原因使许多婴幼儿需要口服给药，给药方法不当容易造成浪费且影响治疗效果，给家长和护理工作带来很大麻烦，现将我们常用的三种喂药方法介绍如下。     

利威口服植物胰岛素：降糖真金不怕火炼

苦瓜作为一种蔬菜和药用植物，几千年来一直用作糖尿病的辅助治疗。但由于其作用弱、起效慢，根本无法与动物胰岛素及降糖西药媲美。近年来，中国科学家在世界上第一次采用“生物酶切”技术，对从苦瓜中提取的类胰岛素多肽进行生物工程处理，获取了具有高效活性的口服植物胰岛素，使每粒胶囊的胰岛素活性含量高达200μIU（国际单位）以上。这是美国、日本等发达国家都做不到的。     

多肽介导肿瘤靶向纳米粒载体的制备及其特性

目的 探讨多肽介导的肿瘤靶向纳米粒载体的制备方法,并评价该载体的特性.方法 合成多肽载体,用磁共振鉴定载体结构,用超声乳化法制备纳米粒载体,电镜下观察纳米粒载体形态,检测粒径和电位.用分光光度法筛选纳米粒临界胶束浓度,用琼脂糖凝胶电泳实验检测多肽载体羧基荧光素标记的小干扰RNA(FAM-siRNA)的包裹能力,用流式细...     

NIDDM患者胰岛素治疗改善口服降糖药的疗效

对于非胰岛素依赖型糖尿病(NIDDM)的治疗,目前国内、外通常提倡的顺序是:(1)基础治疗,即饮食控制和运动疗法;(2)口服降糖药;(3)胰岛素。作者对1组基础治疗恒定、口服降糖药疗效欠佳的病例与用胰岛素后口服降糖药治疗进行自身对照实验,并就NIDDM的药物治疗进行了比较、讨论。     

苦瓜降糖与口服植物胰岛素

近年来,糖尿病药学界对苦瓜的研究日益深入,其中植物胰岛素的发现令人振奋。但新生事物的出现免不了会引起种种猜疑和议论:苦瓜降糖仅仅是登不了大雅之堂的"民间偏方",苦瓜没有胰腺     

Glargine insulin loaded lipid nanoparticles: Oral delivery of liquid and solid oral dosage forms

Background and aimsThe oral administration of insulin has so far been precluded by gastro-intestinal enzyme degradation and poor intestinal absorption. Preliminary evidence for peptide uptake by the gut has recently been obtained, by our research group, following the administration of nanostructured lipid-carrier suspensions loaded with glargine insulin in healthy animal models.Methods and resultsIn this experimental study, glargine insulin-loaded nanostructured lipid carriers have been converted into solid oral dosage forms (tablets, capsules), that are more suitable for administration in humans and have prolonged shelf-life. The liquid and solid oral dosage forms were tested for glargine insulin uptake and glucose responsivity in healthy and streptozotocin-induced diabetic rats (6 animals in each group).A suitable composition gave redispersible solid oral dosage forms from glargine insulin-loaded carriers, using both spray-drying and freeze-drying. It was observed that the liquid and solid formulations had relevant hypoglycaemic effects in healthy rats, while only capsules were efficacious in diabetic rats; probably because of gut alterations in these animal models. Detected glargine insulinaemia was consistent with a glycaemic profile.ConclusionThe formulations under study showed their potential as oral glucose-lowering agents, particularly when used as capsules. However, further study is needed to produce a useful orally-active insulin preparation.     

Effect of oral insulin on insulin autoantibody levels in the Diabetes Prevention Trial Type 1 oral insulin study

Aims/hypothesis Our aim was to evaluate insulin autoantibody (IAA) levels over time in the Diabetes Prevention Trial Type 1 (DPT-1) oral insulin study to determine the effect of oral insulin compared with placebo on IAA levels. Subjects and methods The DPT-1 trial randomised 372 relatives of subjects with type 1 diabetes, positive for IAA and with normal IVGTTs and OGTTs, to oral insulin 7.5 mg daily or placebo. Subjects were followed with IVGTTs, OGTTs and serial IAA measurements. The change in IAA level over time was modelled statistically using mixed model longitudinal data analysis with spatial exponential law for unevenly spaced data. In a separate analysis, subjects were divided into four groups by treatment and diabetes status at the end of the study. IAA levels were compared amongst the groups at randomisation, last sampling and at the maximum level. Results Longitudinal data analysis showed that treatment did not affect levels of IAA over time. After controlling for age, the IAA levels at randomisation and the last visit and the maximum values were different in the four groups. Significantly higher levels were noted in groups that developed diabetes compared with those that did not, with no significant difference by treatment group. Conclusions/interpretation This suggests that IAA levels over time were not influenced by oral insulin in subjects already positive for IAA at the start of treatment. ClinicalTrials.gov ID no.: NCT00004984. Electronic supplementary material The online version of this article (doi:) contains supplementary material, including a list of the members of the DPT-1 Study Group. This is available to authorised users.     

Changes in serum apolipoprotein B concentration after oral glucose or intramuscular insulin

Summary An oral glucose load or a single i.m. insulin injection given to normal human subjects was followed within 1 h by a fall in total serum apolipoprotein B concentration. Although both procedures caused a concomitant drop in serum albumin concentration, the apolipoprotein-B/albumin ratio fell significantly, indicating that the drop in serum apolipoprotein B concentration cannot be explained by hemodilution.     

地特胰岛素用于治疗口服降糖药控制不佳的2型糖尿病患者疗效观察

目的观察地特胰岛素对口服降糖药（OAD）控制不佳的2型糖尿病（T2DM）患者临床疗效。方法33例OAD血糖控制不佳的T2DM患者,加用地特胰岛素每日睡前皮下注射,共24周。观察用药前后FBG、2hBG、HbA1c、BMI等的变化。结果治疗后T2DM患者FBG、2hBG、HbA1C均明显下降（P〈0．01）。日间低血糖发生率9．1％,无夜间症状性低血糖发生,体重无明显增加。结论OAD控制不佳的T2DM患者加用地特胰岛素可有效控制血糖,低血糖发生率低,体重增加不明显。     

Changes of ghrelin following oral glucose tolerance test in obese children with insulin resistance

AIM： To characterize changes in ghrelin levels in response to oral glucose tolerance test （OGTT） and to correlate changes in ghrelin levels with changes in insulin and glucose following OGTT in Chinese obese children of Tanner Ⅰ and Ⅱ stage with insulin resistance. METHODS： 22 obese children with insulin resistance state were divided into four groups according to their Tanner stage and gender： boys of Tanner Ⅰ （fir- Ⅰ ）, boys of Tanner Ⅱ（BT-Ⅱ ）, girls of Tanner Ⅰ （GT- Ⅰ ）, girls of Tanner Ⅱ （GT-Ⅱ）. Ghrelin, insulin and glucose were measured at 0, 30, 60 and 120 rain following OGTT. The control children with normal BMI were divided into control boys of Tanner Ⅰ （CBT- Ⅰ, n = 6）, control boys of Tanner Ⅱ （CBT-Ⅱ, n = 5）, control girls of Tanner Ⅰ （CGT- Ⅰ, n = 6）, control girls of Tanner Ⅱ （CGT-Ⅱ, n = 5）. Fasting serum ghrelin levels were analyzed. RESULTS： Ghrelin levels were lower in obese groups. Ghrelin levels of control group decreased in Tanner Ⅱ stage （CGT- Ⅰ vs CGT-Ⅱ t = -4.703, P = 0.001; CBT- Ⅰ vs CBT- Ⅱ t = -4.794, P = 0.001）. Basal ghrelin levels in fir-Ⅱ decreased more significantly than that in BT- Ⅰ group （t = 2.547, P = 0.029）. Ghrelin levels expressed a downward trend after OGTT among obese children. The decrease in ghrelin levels at 60 min with respect to basal values was 56.9% in BT- Ⅰ. Ghrelin concentrations at 0 min correlated directly with glucose level at 0 min in fir- Ⅰ （r = 0.898, P = 0.015）. There wasn＇t a significant correlation of ghrelin changes with glucose changes and insulin changes during OGTT in obese children with insulin resistance. CONCLUSION： In conclusion, in obese children with insulin resistance, ghrelin levels decreased with advancing pubertal stage. Ghrelin secretion suppression following OGTT was influenced by gender and pubertal stage. Baseline ghrelin levels and ghrelin suppression after OGTT did not significantly correlate with the degree of insulin resistance     

正常糖耐量者口服葡萄糖-胰岛素释放试验的胰岛素分泌曲线特点的研究

目的研究口服葡萄糖一胰岛素释放试验（OGIRT）的胰岛素（Ins）分泌曲线特点,初步探讨适用于I临床评价个体胰岛素敏感性和8细胞分泌功能的方法。方法对12例正常糖耐量者行OGIRT和静脉糖耐量试验（IVGTT）,观察OGIRT、IVGTT血浆Ins分泌峰值时间分布频数,分析胰岛素敏感性和B细胞功能各指标相关指数。结果OGIRT血浆Ins分泌高峰出现于35-45min,无明显第二分泌峰。经多因素线性回归分析表明20、30、35minIns增值与葡萄糖增值的比值（ΔI20／ΔG20、ΔI30／ΔG30、ΔI35／ΔG35）与第一相（1PH）胰岛素分泌、葡萄糖及胰岛素曲线下面积比值（SGI）、胰岛素作用指数（IAI）、HOMA—IR、胰岛素分泌指数均不相关（P〉0．05）,ΔI40／ΔG40与SGI、IAI、HOMA-IR显著相关（P均〈0．01）。结论OGIRT可能不能反映1PH;OGIRTΔI40／ΔG40比I20／ΔG20、△I30／ΔG30能更好地评估β细胞功能。     

Interference at work: a case report of a malfunctioning insulin pump

Insulin pumps operate almost universally in the work environment. Tubeless insulin pumps are a relatively recent development for management of insulin-dependent diabetes. This is the first report of location-dependent failure of insulin pump function, possibly due to external interference, occurring only in the setting of a medical center. A successful solution to this problem was designed and implemented. In conclusion, heightened awareness of this possibility in individuals who use tubeless insulin pumps in a medical environment would seem prudent, as when identified, it can be easily corrected.     

Accurate method to estimate insulin resistance from multiple regression models using data of metabolic syndrome and oral glucose tolerance test

Aims/Introduction

How to measure insulin resistance (IR) accurately and conveniently is a critical issue for both clinical practice and research. In the present study, we tried to modify the β‐cell function, insulin sensitivity, and glucose tolerance test (BIGTT) in patients with normal glucose tolerance (NGT) and abnormal glucose tolerance (AGT) by oral glucose tolerance test (OGTT) and metabolic syndrome (MetS) components.

Materials and Methods

There were 327 participants enrolled and divided into NGT or AGT. Data from 75% of the participants were used to build the models, and the remaining 25% were used for external validation. Steady‐state plasma glucose (SSPG) concentration derived from the insulin suppression test was regarded as the standard measurement for IR. Five models were built from multiple regression: model 1 (MetS model with sex, age and MetS components); model 2 (simple OGTT model with sex, age, plasma glucose, and insulin concentrations at 0 and 120 min during OGTT); model 3 (full OGTT model with sex, age, and plasma glucose and insulin concentrations at 0, 30, 60, 90, 120, and 180 min during OGTT); model 4 (simple combined model): model 1 and model 2; and model 5 (full model): model 1 and 3.

Results

In general, our models had higher r² compared with surrogates derived from OGTT, such as homeostasis model assessment‐insulin resistance and quantitative insulin sensitivity check index. Among them, model 5 had the highest r² (0.505 in NGT, 0.556 in AGT, respectively).

Conclusions

Our modified BIGTT models proved to be accurate and easy methods for estimating IR, and can be used in clinical practice and research.     

口服降糖药与胰岛素对妊娠糖尿病患者分娩方式及新生儿影响的荟萃分析

目的评价口服降糖药与胰岛素对妊娠糖尿病患者分娩方式及新生儿的影响。方法检索1990年1月～2011年2月发表的有关口服降糖药与胰岛素对妊娠糖尿病患者剖宫产率、新生儿低血糖、新生儿出生体重、大于胎龄儿出生率影响的随机对照试验。结果纳入荟萃分析的文献共8篇,包含1538个研究对象。口服降糖药组与注射胰岛素组剖宫产发生率、新生儿低血糖、新生儿出生体重及大于胎龄儿出生率比较差异无统计学意义（P〉0．05）。结论口服降糖药与胰岛素对妊娠糖尿病患者分娩方式及新生儿影响无显著性差异。     

Oestrogens and insulin secretion

There is a persistent perception that oestrogens have an adverse effect on carbohydrate metabolism. It might therefore be expected that their use would result in a corresponding increase in the incidence of diabetes. Recent evidence from clinical trials suggesting that women on postmenopausal oestrogen hormone replacement therapy (HRT) have a reduced incidence of type 2 diabetes therefore appears paradoxical. Short-term supraphysiological oestrogen administration has an adverse effect on glucose tolerance, resulting from suppression of first-phase insulin secretion and increased insulin resistance. Oestrogen-induced increases in glucocorticoid activity could account for these effects. Oestrogen-induced deterioration in glucose tolerance is, however, accompanied by a reduction in fasting glucose, an effect that could be accounted for by glucagon antagonism. These short-term effects contrast with long-term preservation of insulin secretion and glucose homeostasis by oestrogens. In animal studies, ovariectomy is associated with decreased insulin secretion and increased risk of diabetes, whereas oestrogen administration protects against diabetes and increases the insulin response to glucose. The mechanism is uncertain, but direct effects on the pancreas via steroid receptors or indirect effects via oestrogen-induced glucagon antagonism and subclinical increases in glucocorticoids and growth hormone could all contribute. Recent evidence that HRT increases the risk of cardiovascular disease suggests that it should not be used for the prevention of diabetes, but the mechanism responsible for this benefit merits further investigation and might lead to new therapies.Electronic Supplementary Material Supplementary material is available in the online version of this article at