N-糖链抑制剂对高糖刺激鼠肾系膜细胞粘着斑激酶表达及透明质酸分泌的影响

目的：观察N-糖链抑制剂衣霉素(TM)和1-deoxymannojirimycin(DMM)对高糖刺激肾小球系膜细胞(GMC)增生、粘着斑激酶(FAK)表达及透明质酸(HA)分泌的影响。方法：体外培养大鼠GMC，分为七组：正常组，高糖组，甘露醇组，高糖加衣霉素组，高糖加DMM组，并设TM、DMM对照组。采用四唑盐比色(MTT)法测定细胞增生，免疫组织化学方法测定粘着斑激酶(FAK)，放射免疫法测定透明质酸(HA)含量。结果：高糖可诱导GMC增生、增加FAK表达及HA分泌。相对于正常培养条件下生长的GMC，N-糖链抑制剂TM和DMM对高糖作用条件下的GMC增生、FAK活性及HA分泌有更为明显的抑制作用。结论：N-糖链抑制剂TM和DMM可通过阻断糖链的合成和改变糖链类型抑制高糖诱导的细胞增生、FAK活性及HA分泌的作用。     

A case control study on HDL associated PON1 enzyme level in Northern Indian type 2 diabetes mellitus patients

Aim

To evaluate the serum paraoxonase 1 activity and determine its association with duration in type 2 Diabetes mellitus patients.

急性冠脉综合征患者血糖变异性与冠脉病变程度相关性研究

目的比较合并糖尿病的急性冠状动脉综合征（ACS）患者和无糖尿病ACS患者临床特点的差异，并研究ACS患者住院期间血糖变异性与冠脉狭窄程度相关性。方法记录878例ACS患者基线时各指标、临床特点、住院期间不良事件发生情况以及住院期间所有测得的血糖结果，计算每例患者住院期间血糖的平均值、变异系数。（1）将878例ACS患者按照入院前有无糖尿病史分为合并糖尿病的ACS组和无糖尿病ACS组，对记录的主要资料进行回顾性分析，比较各组临床特点；（2）将所有ACS患者分别按照其住院期间血糖变异性或住院期间平均血糖水平各分4组（四分位法），比较各组冠脉病变特点；（3）多元逐步回归分析冠脉病变严重程度（指标为gensini狭窄分数）的相关因素。结果（1）合并糖尿病的ACS患者较之无糖尿病者年龄更大，体重指数更高，多为女性，吸烟、高血压、高胆固醇血症、高甘油三酯血症所占比例更高，高密度脂蛋白-胆固醇平均水平更低、纤维蛋白原平均水平更高，更少接受经皮冠状动脉介入治疗或冠状动脉旁路移植术等积极心脏治疗措施，住院期间死亡率及其他住院期间不良事件发生率、冠脉狭窄分数更高且上述差异均有显著性；尿酸平均水平、低密度脂蛋白-胆固醇平均水平低于无糖尿病者，但无显著性差异。（2）将所有ACS患者分别按照其住院期间血糖变异性分为4组（四分位法），发现随血糖变异性增大，冠脉病变支数增多、冠脉狭窄分数升高。按照住院期间血糖平均水平分组时其结果也相同。（3）ACS患者住院期间血糖变异性与冠脉狭窄程度独立相关。结论阳性糖尿病史、住院期间平均血糖水平高、血糖变异性大均提示冠状动脉病变程度重、近期预后不良。应临床重视ACS患者血糖的监测并加强对ACS患者的血糖控制。     

Circulating IL-18 concentration is associated with insulin sensitivity and glucose tolerance through increased fat-free mass

Aims/hypothesis Knowledge of the factors which simultaneously contribute to insulin-resistance-related inflammation may contribute to early therapeutic targeting. IL-18 has recently been described as one of the factors which, in addition to insulin resistance, may also contribute to atherosclerosis. However, the source of IL-18 is not well characterised.Materials and methods We aimed to study body composition (bioelectric impedance), glucose tolerance (OGTT) and insulin sensitivity (minimal model method) in relation to serum IL-18 (ELISA) concentration in 144 otherwise healthy men aged 51.9±12.5 years.Results In contrast to previous observations in women, circulating IL-18 was not significantly associated with BMI (r=0.12, p=0.1) or WHR (r=0.08, p=0.3). IL-18 was also not associated with absolute or percent fat mass (bioelectric impedance, p>0.20) but, interestingly, it was significantly linked to fat-free mass (p=0.03). Serum IL-18 increased with each quartile of fat-free mass, corresponding to values of 64.2; >64.2 to 71.6; >71.6 to 80.9; and 80.9 kg (ANOVA, p<0.0001). IL-18 was more closely associated with postload glucose during an OGTT (p=0.04) rather than with fasting glucose (p=0.1). HbA₁c (p=0.03), HDL-cholesterol (p=0.04) and serum triglycerides (p=0.03) and parameters of systemic inflammation (C-reactive protein, p=0.02) were also significantly associated with circulating IL-18. Insulin sensitivity (minimal model analysis) was linked to circulating IL-18 (p=0.01). In a multiple linear regression analysis this relationship remained significant after controlling for BMI, age and glucose tolerance status. In another model, both fat-free mass and insulin sensitivity contributed to 10% of IL-18 variance.Conclusions/interpretation Fat mass does not seem to influence circulating IL-18, as initially proposed. In contrast, the fat-free mass compartment (a well-known confounder in the evaluation of insulin sensitivity) may significantly contribute to the relationship between IL-18 and insulin action.     

Non-enzymatic glycosylation of serum proteins as an indicator of diabetic control

Summary In 44 diabetic patients treated either with insulin or with oral antidiabetic agents, non-enzymatic glycosylation of serum proteins (GSP), expressed as nmol of 5-hydroxymethylfurfural/mg protein, showed higher values than those found in control subjects. In the diabetics GSP was more closely correlated to the degree of glycometabolic control during the 15 days preceding the assay, than to the glycosylated hemoglobin (HbAl). However, GSP values did not correlate significantly with fasting blood glucose levels. It may be concluded that GSP can be used as an index of the medium-term control of diabetes mellitus.     

胰岛素抵抗对糖耐量正常冠心病患者冠脉病变的影响

目的探讨胰岛素抵抗对糖耐量正常冠心病患者冠脉病变的影响。方法以112例冠心病患者为研究对象,采用自我平衡模型分析法(homeostasismodelassessment,HOMA)指数作为评价胰岛素抵抗的指标,将患者分为胰岛素抵抗组和胰岛素敏感组,应用多元逐步回归分析对相关危险因素进行分析。结果两组患者多支冠脉病变的发生率差异有统计学意义,弥漫性病变的发生率差异有极显著性意义,体重指数、收缩压、空腹血浆胰岛素、总胆固醇、甘油三酯与冠脉病变程度正相关,高密度脂蛋白-胆固醇与之呈负相关。结论冠心病合并胰岛素抵抗患者冠脉多支病变、多处病变及弥漫性病变的发生率高,提示胰岛素抵抗及其所造成的肥胖、高血压、脂质代谢紊乱是冠心病的独立危险因素。     

Ischemia-reperfusion model in rat spinal cord: cell viability and apoptosis signaling study

This work aimed at determining the ideal ischemia time in an in vitro ischemia-reperfusion model of spinal cord injury. Rat spinal cord slices were prepared and then exposed or not to oxygen deprivation and low glucose (ODLG) for 30, 45, 60, 75 and 90 minutes. Cell viability was assessed by triphenyltetrazolium (TTC), lactate dehydrogenase (LDH) release, and fluorochrome dyes specific for cell dead (ethidium homodimer) using the apotome system. Glutamate release was enzymatically measured by a fluorescent method. Gene expression of apoptotic factors was assessed by real time RT-PCR. Whereas spinal cord slices exposed to ODLG exhibited mild increase in fluorescence for 30 minutes after the insult, the 45, 60, 75 and 90 minutes caused a 2-fold increase. ODLG exposure for 45, 60, 75 or 90 minutes, glutamate and LDH release were significantly elevated. nNOS mRNA expression was overexpressed for 45 minutes and moderately increased for 60 minutes in ODLG groups. Bax/bcl-xl ratio, caspase 9 and caspase 3 mRNA expressions were significantly increased for 45 minutes of ODLG, but not for 30, 60, 75 and 90 minutes. Results showed that cell viability reduction in the spinal cord was dependent on ischemic time, resulting in glutamate and LDH release. ODLG for 45 minutes was adequate for gene expression evaluation of proteins and proteases involved in apoptosis pathways.     

APPL1 acts as a protective factor against podocytes injury in high glucose environment

APPL1, an intracellular adaptor protein, takes part in numerous metabolic reactions. Although APPL1 plays a key role in glucose metabolism via adiponectin pathway and has been proved associated with type 2 diabetes, little is known about its role in diabetic nephropathy. To explore the role of APPL1 in diabetic nephropathy, we upregulated the expression of APPL1 in cultured mouse podocytes by adenovirus infection and tested the effects of APPL1 overexpression in podocytes treated with high glucose. Here, a mouse podocyte cell line (generated from H-2Kb-tsA58 immortmouse) was cultured and divided into four groups: Group 1 (normal glucose, NG), Group 2 (high glucose, HG), Group 3 (HG and infected with control adenovirus) and Group 4 (HG and infected with Ad-APPL1). Cell vitality of Group 4 is significantly higher than Group 2, but notably lower than Group 1 (P<0.01). The apoptosis rate of Group 4 was much lower (P<0.01) than Group 2 and Group 3. A decrease in phase G0/G1 and an increase in phase S was observed in Group 4 compared with Group 2 (P<0.01). These data suggested the protective role of APPL1 overexpression in high glucose condition. Moreover, the levels of Nephrin, AMPK and p-AMPK were decreased by high-glucose treatment, but increased by APPL1 overexpression. In conclusion, in the experimental high glucose condition, APPL1 acts as a protective factor against podocytes injury through regulating AMPK signaling, and may be a new therapy target for diabetic nephropathy.     

The investigation of glucose metabolism and insulin secretion in subjects of chronic hepatitis B with cirrhosis

Aims: To investigate the situations of abnormal glucose metabolism and dysfunction of pancreatic islet beta cells in subjects of chronic hepatitis B (CHB) with cirrhosis. Methods: 106 hepatitis B virus (HBV) positive subjects with liver cirrhosis as well as with different grade of Child-Pugh and 37 healthy subjects were included in this study. The oral glucose tolerance test (OGTT), C-peptide and insulin release test were detected. Plasma glucose and insulin levels were analyzed periodically for 2 h after oral glucose loading. Results: There was no significant difference in the level of fasting plasma glucose and C-peptide between cirrhosis group and control group (P>0.05). The levels of OGTT 2 h glucose, insulin and C peptide were significantly higher in cirrhosis group than control group (P<0.01). Peak plasma glucose levels were obtained at 60 min in normal group and cirrhosis group. The peak insulin and C-peptide response occurred at 60 min in normal group, whereas it was delayed to 120 min in cirrhosis group. There was a significant difference between two groups in the pattern of plasma glucose levels at corresponding time points (P<0.05). The OGTT 2 h glucose and insulin levels were positively correlated with Child-Pugh Score (r1 = 0.389, r2 = 0.508, P<0.01). Conclusion: These findings implied that there was a certain degree of insulin resistance and abnormal glucose metabolism in the patients with liver cirrhosis.