Alterations of proteasome activities in skeletal muscle tissue of diabetic rats

During the last years many investigations have shown that a major catalyst within the mechanism of skeletal muscle wasting occuring under conditions like sepsis, injuries, trauma, cancer cachexia, chronic acidosis, fasting, glucocorticoid treatment, and insulinopenia is the ubiquitin-proteasome system. Evidence for this was obtained by findings that the rate of ATP-dependent protein degradation is increased, that m-RNA concentrations of several proteasome subunits and ubiquitin are increased and the amount of ubiquitin-protein conjugates is elevated under these conditions. Additionally, the enhanced protein breakdown was shown to be suppressed by proteasome inhibitors. In the present report we show that most but not all of the proteolytic activities of partially purified 20S/26S proteasomes from skeletal muscle of rats increase after induction of Diabetes mellitus. This finding suggests that part of the mechanism of acceleration of muscle protein breakdown is due to changes in proteasome activities.     

孕期个性化营养干预对妊娠期糖尿病孕妇糖脂水平及妊娠结局的影响

目的:探讨孕期个性化营养干预对妊娠期糖尿病孕妇糖脂水平及妊娠结局的影响。方法:选择2016年8月-2017年10月期间于我院产检的妊娠期糖尿病孕妇160例,以随机数字表法分为研究组(n=80)和对照组(n=80)。对照组给予常规营养干预,研究组则予以孕期个性化营养干预。比较两组干预前后空腹血糖、餐后2h血糖、总胆固醇(TC)、三酰甘油(TG)、高密低脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平,观察孕妇及新生儿并发症发生情况。结果:干预后两组孕妇空腹血糖、餐后2 h血糖显著降低,且研究组低于对照组(P0.05)。干预后对照组孕妇TC、TG、LDL-C较干预前显著升高(P0.05),HDL-C差异无统计学意义(P0.05),研究组血脂水平与干预前比较差异无统计学意义(P0.05),与对照组比较,研究组孕妇TC、TG、LDL-C水平更低(P0.05)。研究组妊娠期高血压、胎膜早破发生率均明显低于对照组(P0.05),两组感染、产后出血发生率比较无统计学差异(P0.05)。与对照组比较,研究组新生儿窘迫、巨大儿、新生儿低血糖、早产儿的发生率降低(P0.05)。结论:孕期个性化营养干预可有效改善妊娠期糖尿病孕妇的糖脂水平,且能够有效降低并发症发生率,从而改善妊娠结局。     

Na+/Ca2+ exchange of isolated sarcolemmal membrane: effects of insulin,oxidants and insulin deficiency

In this study we prepared sarcolemmal fractions from bovine and rat hearts; their Na⁺K⁺ ATPase activities, measured in the presence of saponin to unmask latent Na⁺K⁺ ATPase, were 59.4 and 48.8 µ mol Pi/mg protein · h, respectively. The rate of Na⁺dependent Ca2⁺ uptake was linear for the first 10 s and a plateau was reached in 3 min. Oxidation by free radical generation either with H₂O₂, FeSO₄ plus DTT or xanthine oxidase plus hypoxanthine stimulated Na⁺/Ca²⁺ exchange in a time-dependent manner. The stimulation was abolished by deferoxamine or o-phenanthroline. By contrast, oxidation by HOCI inhibited Na⁺/Ca²⁺ exchange in proportion to its concentration, and this inhibition was antagonized by DTT. DTT alone had no effect on the exchange. Insulin stimulated Na⁺/Ca²⁺ exchange, its maximal effect was attained after 30min incubation with 100 µ units/ml. N-ethylmaleimide inhibited the exchange both in the presence and in the absence of insulin. Sarcolemmal fractions prepared from hearts of alloxan-treated, acutely diabetic rats showed a significant decrease in Na⁺/Ca²⁺ exchange. Addition of insulin in vitro significantly stimulated Na⁺/Ca²⁺ exchange of both diabetic and control groups. The results indicate that sarcolemmal Na⁺/Ca²⁺ exchange function is modulated by oxidation-reduction states and by the presence of insulin.     

糖适平对2 型糖尿病合并糖尿病肾病4 期患者血糖、肌酐清除率及尿蛋白水平的影响

目的:探讨糖适平对2型糖尿病合并糖尿病肾病4期患者血糖、肌酐清除率及尿蛋白水平的影响。方法:选择我院收治的2型糖尿病合并糖尿病肾病4期患者100例,按照用药情况分为糖适平实验组和胰岛素对照组,每组50例。对照组患者给予预混人胰岛素及阿卡波糖片,实验组患者给予糖适平及阿卡波糖片。比较治疗前后两组患者空腹血糖(FBG)、肌酐清除率(CCr)、血清肌酐(SCr)、血尿素氮(BUN)及24小时尿蛋白定量(24 h Upro)水平的变化情况。结果:与治疗前相比,两组患者治疗后空腹血糖、血清肌酐、血尿素氮及24小时尿蛋白定量、肌酐清除率均明显改善,差异具有统计学意义(P0.05),但实验组与对照组比较差异无统计学意义(P0.05)。结论:糖适平对2型糖尿病合并糖尿病肾病4期患者无药物积蓄问题,用于治疗2型糖尿病合并糖尿病肾病4期安全有效。     

雌性小鼠不适于构建HFD-STZ联合诱导的2型糖尿病模型

目的 探讨雌性小鼠在高脂饲料(HFD)-链脲佐菌素(STZ)联合诱导2型糖尿病模型中的可行性.方法 分别以高脂饲料、高脂饲料-果糖饮水(HFDF)和常规饲料(对照)喂养3周龄的封闭群ICR和近交系C57BL/6J (B6)小鼠6周后,HFD和HFDF组腹腔注射STZ,对照组注射相应体积柠檬酸钠溶液,然后分别以相应饲料继续喂养6周.每周测定小鼠体重,于注射前1周和注射后1～4周测定非空腹血糖浓度.结果 实验结束时各组小鼠体重较初始体重均显著增加.ICR小鼠HFD和HFDF组体重与对照组S无差异,HFD与HFDF组间也无显著变化.虽然B6小鼠HFD与HFDF组体重组间差异不显著,但两组体重均显著低于对照组.注射STZ后1～4周,两品系小鼠HFD与HFDF组血糖水平没有显著升高,组间也没有显著差异,且均没有达到2型糖尿病小鼠成模非空腹血糖标准(11 mmol/L).结论 果糖饮水不能促进高脂饲料诱导的育肥作用,而雌性小鼠也不是HFD-STZ联合诱导2型糖尿病模型的理性选择.     

Interleukin-1ß is a positive regulator of TIARP/STAMP2 gene and protein expression in adipocytes in vitro

The impact of interleukin (IL)-1ß on tumor necrosis factor α-induced adipose-related protein (TIARP)/six-transmembrane protein of prostate 2 (STAMP2) was determined in adipocytes. TIARP/STAMP2 mRNA synthesis was significantly stimulated by IL-1ß in a dose- and time-dependent fashion in 3T3-L1 adipocytes. Signaling studies suggested that janus kinase 2, nuclear factor κB, and p44/42 mitogen-activated protein kinase are involved in IL-1ß-induced TIARP/STAMP2 mRNA expression. Furthermore, IL-1ß, TNFα, and IL-6 showed synergistic stimulatory effects on TIARP/STAMP2 gene expression. Moreover, both TIARP/STAMP2 mRNA synthesis and protein expression were induced by IL-1ß in fully differentiated human mesenchymal stem cell-derived adipocytes (hMSC-Ad). Taken together, TIARP/STAMP2 is highly upregulated in 3T3-L1 cells and hMSC-Ad by IL-1ß and might, therefore, modulate proinflammatory and insulin resistance-inducing effects of IL-1ß.     

测定糖尿病患者血清LDL-C水平的方法学比较

目的：比较不同方法检测糖尿病患者血清LDL-C水平,为临床诊疗提供准确可行的检验方法。方法：采用沉淀法、匀相法、电泳法及超速离心法对233例糖尿病患者和102例健康人群的血清LDL-C水平进行测定,比较各方法之间的相关性,同时分析导致结果差异的因素。结果：四种方法检测健康人群LDL-C水平,结果间无统计学差异（P〉0.05）;糖尿病组,当TG≤2.26mmol/L时,四种方法检测LDL-C结果间相关性良好。高胆红素、血红蛋白、高TG及乳糜等干扰因素存在时,与其他方法相比,电泳法和超速离心法检测血清LDL-C结果受影响较小（P〉0.05）。结论：超速离心法虽耗时、价格贵,但仍为检测LDL-C的经典方法,电泳法受高胆红素、血红蛋白、高三酰甘油等干扰因素的影响相对较小,适用于糖尿病合并高血脂患者血清LDL-C水平检测。     

Molecular and cellular key players in human islet transplantation

Human islet transplantation could represent an attractive alternative to insulin injections for the treatment of diabetes type 1. However, such an approach requires a better understanding of the molecular and cellular switches controlling β-cell function in general as well as after transplantation into the liver. Although much research has been done into the suitability of stem or progenitor cells to generate a limitless supply of human β-cells, a reproducible and efficient protocol for the differentiation of such cells into stably insulin-secreting β-cells suitable for transplantation has yet to be reported. Fueled by recent findings showing that mature β-cells are able to regenerate, many efforts have been undertaken to expand this cell pool. Unfortunately, also these approaches had problems to yield sufficiently differentiated human islet cells. The aim of this review is to summarize recent findings describing some of the molecular and cellular key players of islet biology. A more complete understanding of their orchestration and the use of new methods such as real time confocal imaging for the assessment of islet quality may yield the necessary advancements for more successful human islet transplantation.     

Increase in DPP-IV in the intestine, liver and kidney of the rat treated with high fat diet and streptozotocin

High fat diet or insulin deficiency is commonly seen in Type II diabetes, while the mechanism remains unclear. To test our hypothesis that DPP-IV contributes to Type II diabetes, we examined the expression and activity of DPP-IV in rats (n=8 to each group) treated for 12 weeks with 3 separate diets: a) normal control; b) a high fat diet; and c) a high fat diet plus streptozotocin, a chemical for induction of insulin-deficient diabetes. Compared to rats on the normal diet, the rats with a high fat diet significantly increased DPP-IV's expression and activity about 142-152% in the intestine (P<0.05) and 153-240% in kidneys (P<0.05), but there was no change in the liver. Administration of streptozotocin to the rats treated with the high fat diet showed an insufficient insulin secretion and higher blood glucose in response to glucose/insulin tolerance test, and an increase in expression of DPP-IV and activity by 188-242% in the intestine (P<0.01); 191-225% in liver (P<0.01); and 211-321% in the kidneys (P<0.01). Immunohistochemistry studies confirmed the above results, showing increased DPP-IV immunostaining localized primarily in intestinal epithelium, hepatocytes and renal tubular cells. This study, for the first time reports an increase in DPP-IV associated with a high fat diet, as well as in the combination of a high fat diet with an insulin deficiency. Since both high fat diet and insulin deficiency are closely linked with etiology of Type II diabetes, the evidence in this study suggests a role of DPP-IV in development of Type II diabetes.     

测定糖尿病患者血清LDL-C 水平的方法学比较

目的:比较不同方法检测糖尿病患者血清LDL-C水平,为临床诊疗提供准确可行的检验方法。方法:采用沉淀法、匀相法、电泳法及超速离心法对233例糖尿病患者和102例健康人群的血清LDL-C水平进行测定,比较各方法之间的相关性,同时分析导致结果差异的因素。结果:四种方法检测健康人群LDL-C水平,结果间无统计学差异(P>0.05);糖尿病组,当TG≤2.26mmol/L时,四种方法检测LDL-C结果间相关性良好。高胆红素、血红蛋白、高TG及乳糜等干扰因素存在时,与其他方法相比,电泳法和超速离心法检测血清LDL-C结果受影响较小(P>0.05)。结论:超速离心法虽耗时、价格贵,但仍为检测LDL-C的经典方法,电泳法受高胆红素、血红蛋白、高三酰甘油等干扰因素的影响相对较小,适用于糖尿病合并高血脂患者血清LDL-C水平检测。