2型糖尿病合并非酒精性脂肪性肝病患者血清视黄醇结合蛋白4水平变化及影响因素的研究

目的 研究T2DM合并非酒精性脂肪性肝病（NAFLD）患者血清视黄醇结合蛋白4（RBP4）水平变化.方法 选取单纯T2DM患者（T2DM） 32例,T2DM合并NAFLD者（T2DM＋NAFLD）31例及正常对照（NC）者34名,测定血清RBP4水平,并计算胰岛β细胞功能指数（HOMA-β）及葡萄糖处置指数（DI）.结果 与其他两组比较,T2DM＋ NAFLD组血清RBP4水平最高（P＜0.05或P＜0.01）,而DI最低（P均＜0.01）.且TG、WC、SBP、DI是RBP4的独立影响因素（P均＜0.05）.RBP4是T2DM合并NAFLD独立危险因素（OR=1.142,P=0.057）.结论 血清RBP4在T2DM＋NAFLD组最高,与胰岛β细胞功能密切相关.     

过氧化物酶体增殖物激活受体-γ激动剂对高脂喂养SD大鼠血清视黄醇结合蛋白4水平的影响

目的 观察高脂喂养及吡咯列酮干预对SD大鼠视黄醇结合蛋白4（RBP4）水平的影响.方法 雄性SD大鼠随机分为3组,分别给予普通饮食（NC组）、高脂（F组）及高脂吡咯列酮（F＋Pio组）干预,第8、12周时行OGTT及胰岛素释放试验（ITT）,评价胰岛功能.检测FPG、血脂、肝功能及血清RBP4水平,并对肝脏、附睾脂肪和肾周脂肪称重,计算肝脏质量/体质量及脂肪质量/体质量.结果 8周后,F组FPG、血脂、胰岛素及OGTT血糖曲线下面积（AUCOGTT）、AUCITT均高于NC组（P＜0.05或P＜0.01）,血清RBP4水平升高（P＜0.01）;12周后,与F组相比,F＋Pio组FPG、胰岛素、TG、TC、AUCOOGTT、AUCITT、肝脏质量/体质量及脂肪质量/体质量和血清RBP4水平降低（P＜0.05或P＜0.01）.结论 PPAR-γ激动剂吡咯列酮能减轻糖脂毒性、改善IR并降低体内RBP4水平.     

Association of Plasma Retinol Binding Protein-4 (RBP4) and Sonographic Grading of Fatty Liver in Obese Iranian Children

Background

The prevalence of obesity and its related comorbidities, such as fatty liver, in children is increasing worldwide mostly due to changes in diet and life-style. Many serological markers have been suggested for screening of fatty liver but investigations for finding more reliable factors are still in progress.

Objectives

This study aimed to investigate the correlation between the level of retinol binding protein-4 (RBP4) in the serum and sonographic grading of fatty-liver severity in obese Iranian children.

Patients and Methods

This case-control, double-blind study involved 51 obese children aged between five and 17 years as the case group. In addition, 35 healthy lean children with no liver problems were selected as the control group. Plasma RBP4 (using an ELISA), serum triglycerides (TG), low-density-lipoproteins (LDL), high-density-lipoproteins (HDL), total-cholesterol (Chol), and body mass index (BMI) were measured. Grading the severity of the fatty liver condition was done by an expert radiologist in the case group.

Results

RBP4 levels in obese children (19 482.9 ± 3 302.2 pg/ml) were higher than those found in the lean control group (14 295.68 ± 2 381.3 pg/ml) (P < 0.05). In the obese patients, RBP4 levels showed a significant correlation with the grade of fatty liver and BMI (P < 0.05).

Conclusions

It was found that the level of RBP4 had a strong correlation with the severity of fatty liver. Therefore, RBP4 may be considered as a useful, noninvasive predictive biomarker of intrahepatic lipid content in obese children prior to using radiological investigations. In particular, abdominal sonography, for the evaluation of intrahepatic lipid content in obese patients, as the sensitivity of a sonography is decreased due to the increased thickness of the abdominal wall as a result of fat deposits.     

Specific binding of fluorescein labelled serum retinol-binding protein to its cell surface receptor in isolated,purified bovine pigment epithelial cells

Purified bovine pigment epithelial cells were labelled specifically with fluorescein tagged serum retinol-binding protein. This labelling was specific for serum retinol-binding protein and for pigment epithelial cells. The fluorescent label was confined to the choroidal surface of the cell. The hemicellular labelling pattern was used for a vectorial orientation of isolated cells, using the melanin pigment as an internal filter for fluorescence. Fluorescent labelled hexokinase, an unrelated protein, did not show specific labelling of pigment epithelial cells. Prealbumin, which circulates in plasma as a tight complex with retinol-binding protein, did not bind to pigment epithelial cells. Retinol-binding protein can act as a bridge between the pigment epithelial cell surface receptor and fluorescein tagged prealbumin. This suggests that the topological sites of the retinol-binding protein molecule for binding to the cell surface receptor and to prealbumin are different.     

Characterization of the proteinuria induced by prolonged oral administration of cadmium in female rats

Female Sprague-Dawley rats were given 200 ppm cadmium (Cd) in the drinking water for 11 months. Total proteinuria and the concentrations of Cd in blood, urine, liver and kidney cortex were determined monthly. The proteinuria was characterized by Sephadex G-75 chromatography and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

From the 8th month of treatment, the Cd concentration in the kidney cortex levels off at a value of about 250 μg/g wet wt and this phenomenon coincides with the occurrece of proteinuria. The proteinuria was characterized by an increased urinary excretion of high molecular weight (HMW) proteins, particularly γ-globulins. Aminoaciduria also increased which suggests the existence of a slight tubular dysfunction. The renal dysfunction induced by chronic oral administration of Cd seems different from that observed in a previous study in which Cd was administered by the i.p. route (1 mg Cd/kg, 5 times a week for 2 months). For the same level of Cd in the kidney cortex the proteinuria induced by i.p. injection of Cd was usually of mixed type and in some cases of the tubular type. The development of this proteinuria was coincident with the levelling off of Cd concentration in the kidney cortex and in the liver. The saturation of liver by Cd is very likely at the origin of the extensive tubular lesion and of the mixed type proteinuria observed in the i.p. experiment. These results demonstrate the importance of the mode of Cd administration on the nature of the Cd-induced proteinuria in animal. They support also our proposal that both low and HMW proteins should be determined in urine for the early detection of renal damage occurring in man chronically exposed to cadmium.     

尿半胱氨酸蛋白酶抑制剂用于评价肾小管早期损伤的研究

目的探讨尿半胱氨酸蛋白酶抑制剞C（CYS-C）用于评估肾小管早期损伤的价值。方法对40例肾病患者测定尿中CYS-C、视黄醇结合蛋白（RBP）和N-乙酰-β-D-氨基葡萄糖苷酶（NAG）,分析阳性检出率及三者的相关性。结果所有患者的CYS-C阳性检出率为60．0％,RBP为57．5％,NAG为67．5％;CYS-C与RBP有显著相关性,差异有统计学意义（r=0．743、P〈0．01）,CYS-C与NAG无相关性,差异无统计学意义（r=0．289、P〉0．05）。结论尿CYS-C与RBP均是提示肾小管早期损伤有效的指标,而且CYS-C的敏感性和稳定性较RBP高,测定方法也优于RBP。     

Performance of the CRAFTi portable fluorometer comparing with the HPLC method for determining serum retinol

Objective

To determine the performance of a portable fluorometer for measuring serum retinol (SR) concentration.

Design and methods

Serum samples were obtained from 75 factory worker women and 143 school children. SR concentration was quantified using a portable fluorometer (‘CRAFTi’) and HPLC analysis.

Results

SR by HPLC (1.23 ± 0.43 μmol/L) and CRAFTi (1.16 ± 0.46 μmol/L) was significantly correlated. Sensitivity and specificity were 85.3% and 78.0% (cutoff of 1.05 μmol/L). Kappa statistics showed moderate agreement.

Conclusions

CRAFTi portable fluorometer is a promising field-friendly tool for screening vitamin A deficiency.     

多种血清联合测定在糖尿病肾病中的应用

目的探讨血清胱抑素C(CysC)、视黄醇结合蛋白(RBP)及β2-微球蛋白(β2-MG)联合检测对糖尿病肾病的临床诊断价值。方法测定100例单纯糖尿病患者、92例糖尿病肾病患者血清CysC水平,同时测定RBP、β2-MG、血尿素(Sur)和血肌酐(Scr)水平,并以100例健康体检者作为对照组。结果糖尿病肾病患者血清CysC、RBP、β2-MG、Sur、Scr明显高于单纯糖尿病组和对照组,差异有统计学意义(P<0.01),且血清CysC、RBP、β2-MG的阳性检出率明显高于Sur、Scr,并且CysC、RBP、β2-MG联合检测优于单项检测。结论糖尿病肾病患者血清Cy-sC、RBP、β2-MG及三者联合测定与对照组比较差异有统计学意义。并且从健康对照组到单纯糖尿病再到糖尿病肾病组血清β2-MG含量逐渐升高,呈进展趋势。而且通过血清CysC、RBP、β2-MG联合测定,可以提高早期糖尿病肾病检出率。     

Cyanidin 3-glucoside ameliorates hyperglycemia and insulin sensitivity due to downregulation of retinol binding protein 4 expression in diabetic mice

Adipocyte dysfunction is strongly associated with the development of obesity and insulin resistance. It is accepted that the regulation of adipocytokine expression is one of the most important targets for the prevention of obesity and improvement of insulin sensitivity. In this study, we have demonstrated that anthocyanin (cyanidin 3-glucoside; C3G) which is a pigment widespread in the plant kingdom, ameliorates hyperglycemia and insulin sensitivity due to the reduction of retinol binding protein 4 (RBP4) expression in type 2 diabetic mice. KK-A(y) mice were fed control or control +0.2% of a C3G diet for 5 weeks. Dietary C3G significantly reduced blood glucose concentration and enhanced insulin sensitivity. The adiponectin and its receptors expression were not responsible for this amelioration. C3G significantly upregulated the glucose transporter 4 (Glut4) and downregulated RBP4 in the white adipose tissue, which is accompanied by downregulation of the inflammatory adipocytokines (monocyte chemoattractant protein-1 and tumor necrosis factor-alpha) in the white adipose tissue of the C3G group. These findings indicate that C3G has significant potency in an anti-diabetic effect through the regulation of Glut4-RBP4 system and the related inflammatory adipocytokines.