α-葡萄糖苷酶抑制剂体外筛选方法的研究

以对-硝基苯-α-D-吡喃葡萄糖苷为底物,通过高效液相色谱定量分析水解产物对-硝基苯酚,确定α-葡萄糖苷酶的活性,建立新的α-葡萄糖苷酶抑制剂的体外筛选方法,为了提高筛选方法的灵敏度,对酶促反应条件进行了优化,并用阿卡波糖验证筛选方法的可靠性,结果测得阿卡波糖的IC50为2.07 mg/mL,与文献报道相近,说明该法可替代传统的Trembly法,并可用于α-葡萄糖苷酶抑制剂的高通量筛选。     

Putative association between a new polymorphism in exon 3 (Arg109Cys) of the pancreatic colipase gene and type 2 diabetes mellitus in two independent Caucasian study populations

The protein encoded by the pancreatic colipase (CLPS) gene is an essential cofactor needed by pancreatic triglyceride lipase (PNLIP) for efficient dietary lipid hydrolysis. Since the inhibition of lipase activity was shown to reduce the incidence of type 2 diabetes mellitus, we tested the hypothesis that genetic variations in the CLPS and PNLIP genes are associated with type 2 diabetes; 47 unrelated subjects were screened for polymorphisms of the CLPS and PNLIP genes. A nested-case control study of 192 incident type 2 diabetes subjects and 384 sex- and age-matched controls taken from the European Prospective Investigation into Cancer and Nutrition Potsdam Cohort (EPIC) was employed for association studies. The Metabolic Intervention Cohort Kiel (MICK) consisting of 716 males was used for verification. A novel putative functional polymorphism (Arg109Cys) was identified in the CLPS gene. The frequencies of the Arg/Cys genotype were 2.6% in EPIC and 2.2% in MICK study subjects. No homozygotes for the Cys/Cys genotype were found in either study population. Logistic regression analysis showed a statistically significant association of the Arg/Cys genotype with an increased risk of type 2 diabetes. The odds ratios estimated by the model were 3.75 (95%CI = 1.13-12.49, p = 0.03) in EPIC and 4.86 (95%CI = 1.13-20.95, p = 0.03) in MICK. No comparable associations were found with other traits of the insulin-resistance syndrome (e. g.; body mass index, waist to hip ratio). In conclusion, we obtained evidence in two German Caucasian study populations that the variant of the rare CLPS Arg109Cys polymorphism might contribute to increased susceptibility of type 2 diabetes.     

L-阿拉伯糖对正常及高糖高脂喂养大鼠生长及糖脂代谢的影响

目的观察L-阿拉伯糖对正常大鼠和高糖高脂喂养大鼠生长及糖脂代谢的影响。方法雄性Wistar大鼠60只,按体重和空腹血糖随机分为6组(n=10):空白对照组、高剂量对照组、模型对照组以及L-阿拉伯糖低、中、高剂量实验组,分别以普通饲料和高糖高脂饲料喂养6周,观察大鼠的体重、食物利用率,测定大鼠的糖脂代谢指标。结果L-阿拉伯糖对正常大鼠的体重、体脂、食物利用率、空腹血糖均无影响;能显著提高正常大鼠的糖耐量(P<0.01);降低正常大鼠的血清甘油三酯(P<0.05)并增高血清高密度脂蛋白胆固醇(P<0.01)。模型对照组和各实验组大鼠的体重、体脂、糖耐量、血清总胆固醇均显著高于空白对照组(P<0.05)。以87.5、175、525mg/kgBW剂量的L-阿拉伯糖灌胃高糖高脂饲料喂养的肥胖模型大鼠6周,各剂量L-阿拉伯糖均能显著改善肥胖模型大鼠的糖耐量(P<0.01),高剂量组大鼠的体脂含量明显下降(P<0.05)。结论L-阿拉伯糖能显著增强正常和高糖高脂喂养大鼠的糖耐量,降低大鼠血清甘油三酯,增高血清高密度脂蛋白胆固醇,并有降低大鼠体脂含量和减缓体重增加的趋势。     

The Health Benefits of Selected Culinary Herbs and Spices Found in the Traditional Mediterranean Diet

The Mediterranean diet is considered one of the healthiest diets in the world. This is often attributed to low saturated fat consumption, moderate wine consumption, and high vegetable consumption. However, herbs and spices associated with these diets may also play an important role in the quality of this diet. This review summarizes the most recent research regarding the anti-diabetic, anti-inflammatory, anti-hyperlipidemic and anti-hypertensive properties of this collection of culinary species. Additionally, this review briefly summarizes studies performed on lesser known herbs from around the world, with the goal of identifying new culinary species that may be useful in the treatment or prevention of diseases.     

Hydro‐ethanolic extract of cashew tree (Anacardium occidentale) nut and its principal compound,anacardic acid,stimulate glucose uptake in C2C12 muscle cells

Scope: Products of cashew tree (Anacardium occidentale) are used in traditional medicine for various ailments, including diabetes. Methods and results: The anti‐diabetic properties of cashew plant parts were studied using differentiated C2C12 myoblasts (myotubes) and rat liver mitochondria. Hydroethanolic extract of cashew seed (CSE) and its active component, anacardic acid (AA), stimulated glucose transport into C2C12 myotubes in a concentration‐dependent manner. Extracts of other parts (leaves, bark and apple) of cashew plant were inactive. Significant synergistic effect on glucose uptake with insulin was noticed at 100 μg/mL CSE. CSE and AA caused activation of adenosine monophosphate‐activated protein kinase in C2C12 myotubes after 6 h of incubation. No significant effect was noticed on Akt and insulin receptor phosphorylation. Both CSE and AA exerted significant uncoupling of succinate‐stimulated respiration in rat liver mitochondria. Conclusion: Activation of adenosine monophosphate‐activated protein kinase by CSE and AA likely increases plasma membrane glucose transporters, resulting in elevated glucose uptake. In addition, the dysfunction of mitochondrial oxidative phosphorylation may enhance glycolysis and contribute to increased glucose uptake. These results collectively suggest that CSE may be a potential anti‐diabetic nutraceutical.     

Novel α-glucosidase inhibitors from Macaranga tanarius leaves

One of the hyperglycaemic remedies is glucose absorption reduction by suppressing carbohydrate digestion due to utilisation of α-glucosidase inhibitors (AGIs). Determination of prospecting herbs done in vitro by using enzyme assay resulted in the finding of Macaranga tanarius, which showed a potent inhibitory activity. An EtOAc-soluble extract of M. tanarius leaves was chromatographed by a Diaion HP-20 column and the active fractions were further purified with high performance liquid chromatography (HPLC) to isolate active principles against α-glucosidase. Five ellagitannins were successfully isolated and identified. Structure determination revealed that these isolated compounds were mallotinic acid (IC₅₀ > 5.00 mM), corilagin (IC₅₀ = 2.63 mM), chebulagic acid (IC₅₀ = 1.00 mM), and two novel compounds named macatannins A (IC₅₀ = 0.80 mM) and B (IC₅₀ = 0.55 mM). AGIs play an important role for the treatment of diabetes, therefore this research results may suggest novel alternatives for diabetes treatment management.     

燕麦β-葡聚糖对2型糖尿病大鼠肠黏膜屏障的影响

目的:探究燕麦β-葡聚糖对2型糖尿病大鼠肠黏膜屏障的影响。方法:雄性SD大鼠高脂饲料喂养4周,腹腔注射链脲佐菌素(streptozotocin,STZ)建立2型糖尿病模型,成模后随机分为模型对照组和燕麦β-葡聚糖低、中、高剂量组。低、中、高剂量组由基础饲料添加燕麦β-葡聚糖至其质量分数分别为0.275%、0.550%、1.100%,模型对照组和正常对照组均以基础饲料喂养。10周后,测定其空腹血糖、肠道菌群以及结肠β-防御素-2、分泌型免疫球蛋白A(secretory immunoglobulin A,s Ig A)、紧密连接蛋白Occludin含量。结果:高剂量组较模型对照组血糖水平显著降低(P0.05);燕麦β-葡聚糖各干预组结肠紧密连接蛋白Occludin的表达水平显著高于模型对照组(P0.05),β-防御素-2水平显著低于模型对照组(P0.05),结肠s Ig A水平与模型对照组之间的差异不显著(P0.05);中、高剂量组结肠大肠杆菌数量上升幅度减小(P0.05),燕麦β-葡聚糖各干预组双歧杆菌、乳酸杆菌数量上升幅度增大(P0.05)。结论:燕麦β-葡聚糖可以改善2型糖尿病大鼠肠黏膜机械屏障和生物屏障的损伤,起到保护肠黏膜屏障的作用。     

Association of Serum Uric Acid Concentration with Diabetic Retinopathy and Albuminuria in Taiwanese Patients with Type 2 Diabetes Mellitus

Patients with type 2 diabetes mellitus (DM) may experience chronic microvascular complications such as diabetic retinopathy (DR) and diabetic nephropathy (DN) during their lifetime. In clinical studies, serum uric acid concentration has been found to be associated with DR and DN. The goal of this study was to evaluate the relationship between the increases in serum uric acid level and the severity of DR and albuminuria in Taiwanese patients with type 2 DM. We recorded serum uric acid concentration, the severity of DR, and the severity of albuminuria by calculating urinary albumin-to-creatinine ratio (UACR) in 385 patients with type 2 DM. In multivariate logistic regression analysis, a high uric acid concentration was a risk factor for albuminuria (odds ratio (OR), 1.227; 95% confidence interval (CI) = 1.015–1.482; p = 0.034) and DR (OR, 1.264; 95% CI = 1.084–1.473; p = 0.003). We also demonstrated that there was a higher concentration of serum uric acid in the patients with more severe albuminuria and DR. In conclusion, an increased serum uric acid level was significantly correlated with the severity of albuminuria and DR in Taiwanese patients with type 2 DM.     

Evaluation of Oxidative Stress Biomarkers,Pro-Inflammatory Cytokines,and Histological Changes in Experimental Hypertension,Dyslipidemia, and Type 1 Diabetes Mellitus

The present study aims to compare the oxidative stress biomarkers, pro-inflammatory cytokines, and histological changes induced by three cardiovascular risk factors, namely, hypertension, dyslipidemia, and type 1 diabetes mellitus. Hypertension was induced with 40 mg/kg body weight (b.w.) of N omega-nitro-L-arginine-methyl (L-NAME) administered orally. Dyslipidemia was induced by the administration of a diet with a high cholesterol (2%) content. Diabetes mellitus was induced by intraperitoneal administration of a single dose of streptozocin (65 mg/kg). Malondialdehyde (MDA) and total oxidative status (TOS) are increased by all three cardiovascular risk factors (up to 207%). The indirect assessment of NO synthesis (NOx) is observed to be reduced after L-NAME administration (43%), and dyslipidemia induction (16%), while type 1 diabetes mellitus is associated with the highest levels of NOx (increased 112%). Hypertension, dyslipidemia, and type 1 diabetes reduced the total antioxidative capacity (TAC) and total thiol (SH) levels (up to 57%). The values of evaluated pro-inflammatory cytokines, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), assessed from the ascending aorta were elevated by all three cardiovascular risk factors, with the highest levels induced by type 1 diabetes mellitus (up to 259%). The histopathological examination of the ascending and descending aorta revealed reversible pro-atherogenic changes consisting of the accumulation of lipid droplets in the subendothelial connective tissue on rats with hypertension and dyslipidemia. Irreversible pro-atherogenic changes consisting of a reduction of the specific elasticity of the arteries were observed in rats with type 1 diabetes mellitus. Type 1 diabetes mellitus demonstrates an alteration of the oxidative stress parameters, the elevation of tissue levels of the pro-inflammatory cytokines and causing irreversible pro-atherogenic changes on the aortic wall.     

Innate Lymphoid Cells: Emerging Players in Pancreatic Disease

Common pancreatic diseases have caused significant economic and social burdens worldwide. The interstitial microenvironment is involved in and plays a crucial part in the occurrence and progression of pancreatic diseases. Innate lymphoid cells (ILCs), an innate population of immune cells which have only gradually entered our visual field in the last 10 years, play an important role in maintaining tissue homeostasis, regulating metabolism, and participating in regeneration and repair. Recent evidence indicates that ILCs in the pancreas, as well as in other tissues, are also key players in pancreatic disease and health. Herein, we examined the possible functions of different ILC subsets in common pancreatic diseases, including diabetes mellitus, pancreatitis and pancreatic cancer, and discussed the potential practical implications of the relevant findings for future further treatment of these pancreatic diseases.