糖尿病性视网膜病变与脂联素的研究进展

糖尿病性视网膜病变是糖尿病最常见的微血管并发症之一,是造成糖尿病患者失明的主要原因,其发生机制尚不完全清楚.从目前已发现脂肪细胞因子参与了糖尿病性视网膜病变的新生血管形成及细胞增殖等一系列病理改变特性出发,对脂联素在糖尿病性视网膜病变的发生发展中的重要作用进行了综述.     

液相色谱-串联质谱法检测人血浆及脂蛋白唾液酸的含量

建立了液相色谱-串联质谱(LC-MS/MS)检测人血浆脂蛋白唾液酸的方法,并比较了糖尿病患者与健康人血浆脂蛋白唾液酸的差异。采用pH=2的醋酸水解唾液酸,高速离心后采用优化的条件进行LC-MS/MS分析。结果表明:在负离子模式下,唾液酸的检出限和定量限分别为7.4和24.5 pg。唾液酸在2.5~80 ng/mL范围内呈良好的线性关系,相关系数R²大于0.998。糖尿病患者(平均年龄51.6岁)和健康人(平均年龄50.7岁)血浆中唾液酸的含量分别为(548.3±88.9)和(415.3±55.5)mg/L;两组实验人群中极低密度脂蛋白、低密度脂蛋白和高密度脂蛋白唾液酸的含量分别为(4.91±0.19)、(6.95±0.28)、(3.61±0.22)μg/mg和(2.90±0.27)、(7.03±0.04)、(2.40±0.09)μg/mg。糖尿病患者极低密度脂蛋白和高密度脂蛋白唾液酸含量显著高于同龄健康人水平(P<0.01)。该法可快速检测血浆中脂蛋白唾液酸含量,省时省力。     

基于血浆中脂肪酸代谢谱及非线性判别分析方法的糖尿病中医证候分型

糖尿病是严重威胁人类健康的代谢综合征之一,中医因在治疗糖尿病方面有着自身的优势和特色而广泛受到重视。该文以血浆中脂肪酸代谢谱及血脂代谢指标为研究对象,结合化学计量学方法,对5种糖尿病中医证候(气虚、阴虚、气阴两虚、热盛和血瘀)进行关联分析。通过正交信号校正的偏最小二乘(OSC-PLS)方法将5种证候与健康组较明显地区分开。同时,采用非线性判别分析(ULDA)对健康组、中医虚证(气虚、阴虚、气阴两虚)、中医实证(热盛、血瘀)进行分析,3组样本体现明显的聚类效果,正判率达到95.7%。其中对分类贡献较大的标志物为二十碳二烯酸(C20:2)、二十碳五烯酸(C20:5)、甘油三酯(TG)和高密度脂蛋白(HDL),这一结果为辅助糖尿病中医临床诊断提供了重要的信息。     

Is the placental proteome impaired in well‐controlled gestational diabetes?

In pregnancy complicated by gestational diabetes mellitus (GDM), the human placenta shows several pathological functional and structural changes, but the extent to which maternal glycemic control contributes to placental abnormalities remains unclear. The aim of this study was to profile and compare the proteome of placentas from healthy pregnant women and those with GDM, to investigate the placenta‐specific protein composition and possible changes of its function in presence of GDM. Quantitative proteomic analysis, based on LC‐MS^E approach, revealed that higher (approximately 15% increase) levels of galectin 1 and collagen alpha‐1 XIV chain (although the difference regarding the latter was at the limit of significance) were present in GDM samples, while heat shock 70 kDa protein 1A/1B was less abundant in GDM placental tissue. These data seem to indicate that GDM, when well controlled, did not markedly affect the placental proteome.     

The hypoglycemic and antioxidant activities of garden cress (Lepidium sativum L.) seed on alloxan-induced diabetic male rats

The hypoglycemic and antioxidants activities of the methanol extract of Lepidium sativum seeds was tested in alloxan-induced diabetic male rats. Thirty male albino rats weighing 190–200 g were divided into five groups as follows: negative control, positive control and three diabetic groups treated with three concentrations of L. sativum methanol extract for four weeks. Induction of hyperglycemia in the positive control group increased blood glucose, glycated hemoglobin A1c, immunoglobulins, liver enzyme, lipid peroxide and kidney function, total cholesterol, low-density lipoproteins, very low-density lipoproteins and decreased antioxidants and high-density lipoproteins compared with the negative control. Furthermore, pancreas tissues showed pathological changes compared with the negative control. Treating the diabetic rats with L. sativum methanol extract decreased blood sugar and restored all biochemical and histological changes to the normal. It could be concluded that L. sativum methanol extract succeeded in controlling diabetes, increasing antioxidants and ameliorating lipid profile.     

Simultaneous determination of five isoflavones in rat plasma by LC‐MS/MS: Comparative pharmacokinetic characteristics of Puerariae lobatae radix in normal and type 2 diabetic rats

A rapid and sensitive liquid chromatography with tandem mass spectrometry method was developed and validated for simultaneous determination of puerarin, daidzin, daidzein, 3′‐hydroxy puerarin, and genistein in rat plasma after oral administration of Puerariae lobatae radix extract. The method of protein precipitation with acetonitrile was used for sample preparation. Chromatographic separation was achieved on a C₁₈ column with the mobile phases of acetonitrile/water containing 0.1% formic acid. The analytes were detected by mass spectrometer with an electrospray ionization source operating in the negative ion mode. The linearity, precision, accuracy, dilution reliability, recovery, matrix effects, and stability of the method were within acceptable ranges. The developed method was successfully used to compare the pharmacokinetic characteristics of five analytes in normal and type 2 diabetics rats after oral administration of Puerariae lobatae radix extract. Several pharmacokinetic alterations were observed and this might be caused by the pathological state of type 2 diabetes.     

A tolbutamide–metformin salt based on antidiabetic drug combinations: synthesis,crystal structure analysis and pharmaceutical properties

A drug–drug anhydrous pharmaceutical salt containing tolbutamide {systematic name: 3‐butyl‐1‐[(4‐methylbenzene)sulfonyl]urea, TOL, C₁₂H₁₈N₂O₃S} and metformin (systematic name: 1‐carbamimidamido‐N,N‐dimethylmethanimidamide, MET, C₄H₁₁N₅) was created based on antidiabetic drug combinations to overcome the poor pharmaceutical properties of the parent drugs. Proton transfer and the proportion of the two components were confirmed by ¹H NMR spectroscopy and single‐crystal X‐ray diffraction analysis. Comprehensive characterization of the new pharmaceutical salt crystal, 2‐[(dimethylamino)(iminiumyl)methyl]guanidine (butylcarbamoyl)[(4‐methylbenzene)sulfonyl]azanide, C₄H₁₂N₅⁺·C₁₂H₁₇N₂O₃S^?, was performed and showed enhancement of the pharmaceutical properties, such as lower hygroscopicity and greater accelerated stability than the parent drug MET, and higher solubility and dissolution rate than TOL. The property alterations were correlated with the crystal packing features and potential hydrogen‐bonding sites through observed changes in the crystal structures.     

Beneficial Effect of Quercetin on Erythrocyte Properties in Type 2 Diabetic Rats

Diabetes mellitus is characterized by tissue oxidative damage and impaired microcirculation, as well as worsened erythrocyte properties. Measurements of erythrocyte deformability together with determination of nitric oxide (NO) production and osmotic resistance were used for the characterization of erythrocyte functionality in lean (control) and obese Zucker diabetic fatty (ZDF) rats of two age categories. Obese ZDF rats correspond to prediabetic (younger) and diabetic (older) animals. As antioxidants were suggested to protect erythrocytes, we also investigated the potential effect of quercetin (20 mg/kg/day for 6 weeks). Erythrocyte deformability was determined by the filtration method and NO production using DAF-2DA fluorescence. For erythrocyte osmotic resistance, we used hemolytic assay. Erythrocyte deformability and NO production deteriorated during aging—both were lower in older ZDF rats than in younger ones. Three-way ANOVA indicates improved erythrocyte deformability after quercetin treatment in older obese ZDF rats only, as it was not modified or deteriorated in both (lean and obese) younger and older lean animals. NO production by erythrocytes increased post treatment in all experimental groups. Our study indicates the potential benefit of quercetin treatment on erythrocyte properties in condition of diabetes mellitus. In addition, our results suggest potential age-dependency of quercetin effects in diabetes that deserve additional research.     

钒化合物抗糖尿病作用的研究进展*

在糖尿病的治疗研究中,体内和体外的研究表明,钒化合物可以降低I型和II型糖尿病血糖,促进葡萄糖转运和糖原合成,具有“类胰岛素作用”。本文综述了近年来钒化合物在降低和改善糖尿病症状的生物效应及其通过胰岛素信号通路在降糖作用的分子机制的研究进展。     

糖尿病治疗模型中技术时滞诱发的双Hopf分岔

本文研究了利用外部辅助设备来治疗糖尿病的生理模型,其中存在着两个时滞;辅助设备的技术时滞τ1和肝脏的生理时滞τ2。发现由于技术时滞τ1的出现,使模型存在着共振和非共振的双Hopf分岔。应用非线性动力学理论,对由此产生的非共振分岔的动力学行为进行了分类。结果表明,随着技术时滞τ1和糖尿病人患病程度α的变化,利用该模型可以预测不同的医疗结果：血糖稳定（康复）、简单的和复杂的血糖波动。结果对分析、预测、优化糖尿病治疗方案的医疗结果、评估该方案的医疗风险和可行性等有着潜在的应用价值。本文结果的意义在于针对糖尿病患者患病的不同程度,可以定性的调节辅助设备的技术时滞τ1,以达到更好的治疗效果。