C肽对GK大鼠糖尿病肾病的影响

目的研究C肽对糖尿病肾病GK大鼠肾脏病理和肾脏功能的影响及相关机制。方法SPF级自发性糖尿病GK大鼠,在糖尿病发病并且24小时尿蛋白超过300mg后,随机分为3组：C肽治疗组、空白对照组和胰岛素治疗组,每组8只,持续治疗12周。以同龄的正常Wistar大鼠作为正常组。治疗前及治疗后每4周检测各组大鼠血糖、24小时尿蛋白以及24小时尿白蛋白。治疗结束后,取各组大鼠肾脏,透射电子显微镜观察大鼠肾脏肾小球病理改变。采用实时定量PCR、westernblot以及免疫组织化学的方法检测肾小球RAGE、PKC－6和PKA的表达。采用单因素方差分析评价各组间的差异。结果与正常组相比,空白对照组的血糖、24小时尿蛋白和24小时尿白蛋白都明显升高：虽然C肽治疗组大鼠的血糖没有明显改变,但24小时尿蛋白和24小时尿白蛋白与空白对照组相比都明显减少;胰岛素治疗组的血糖明显降低,但24小时尿蛋白和24小时尿白蛋白与空白对照组相比没有明显差异。病理学检查显示,与空白对照组相比,C肽治疗组大鼠的肾小球硬化、肾小球系膜增生、基底膜厚度和足细胞的形态都明显改善,而胰岛素治疗不具有类似的作用。实时定量PCR、westernblot和免疫组织化学结果显示,C肽能够显著下调RAGE和PKC—β在糖尿病肾病大鼠肾小球的表达,并显著上调PKA的表达;而胰岛素仅能明显下调RAGE,对PKC、PKA的表达没有明显调节作用。结论C肽可能通过下调。肾小球毛细血管RAGE、PKC－β的表达和上调PKA的表达而改善GK大鼠的糖尿病肾病。     

Serum levels of glucose,insulin, and C-peptide during long-term D-ribose administration in man

Summary D-ribose was given orally and/or intravenously to nine healthy subjects at doses ranging from 83.3 to 222.2 mg/kg per hour for at least four hours. The serum ribose level increased in a dose-dependent manner to maximum concentrations of 75 to 85 mg/dl. The serum glucose level decreased after the beginning of continuous ribose administration and was reduced as long as ribose was being administered. The oral or intravenous administration of 166.7 mg/kg per hour of ribose resulted in a 25% decrease in serum glucose. Higher intravenous doses of ribose did not provoke a further decrease in serum glucose concentration. Oral administration of 166.7 mg/kg per hour led to an increase in serum insulin concentrations from a mean of 8.4 (range 6.4–11.5) to 10.4 (range 6.3–15.4) U/ml (p<0.05). In contrast, intravenous administration did not change serum insulin concentrations significantly. The serum c-peptide concentration remained unchanged regardless of treatment. We conclude that the variations in plasma insulin concentrations do not account for the observed decrease in mean serum glucose concentrations accompanying D-ribose administration.This paper was supported by a grant from the Friedrich-Baur-Stiftung, Federal Republic of Germany     

葛根素对糖尿病大鼠心肌损伤的影响

目的:探讨葛根素对糖尿病大鼠心肌损伤的影响及其机制。方法:雄性SD大鼠随机分成6组:正常对照组,糖尿病模型组,葛根素高(160mg·kg-1)、中(120mg·kg-1)、低(80mg·kg-1)剂量治疗组,氨基胍(100mg·kg-1)治疗组;各组大鼠每天腹腔注射相应药物1次,正常对照组及糖尿病模型组腹腔注射等体积丙二醇。治疗12周后,透射电镜下观察心肌的形态学改变,用生化方法测定血糖浓度、心肌组织中超氧化物歧化酶(SOD)、Ca2+-ATPase、Na+-K+-ATPase活性及丙二醛(MDA)含量,采用RT-PCR检测心肌组织过氧化物酶体增殖物激活受体γ(PPAR-γ)、葡萄糖转运体4(GLUT-4)、醛糖还原酶(AR)的mRNA表达水平。结果:糖尿病组大鼠心肌组织电镜下主要见到心肌细胞肌原纤维减少,纤维间脂滴沉积,线粒体排列紊乱,嵴部分断裂或消失,结构不清;SOD、Ca2+-ATPase、Na+-K+-ATPase活性和PPAR-γ、GLUT-4 mRNA表达明显低于正常对照组(均P0.01),而血糖浓度、MDA含量和AR mRNA表达明显高于正常对照组(均P0.01)。经葛根素治疗后,上述改变逆转,与糖尿病模型组比较差异显著(P0.05或P0.01),电镜下心肌组织形态学病变明显减轻,肌纤维排列较整齐,仅见少量脂滴沉积,大部分线粒体嵴清晰致密。结论:葛根素对糖尿病大鼠心肌具有一定的保护作用,其机制可能与上调PPAR-γ、GLUT-4 mRNA的表达,促进心肌细胞对葡萄糖的摄取,减轻氧化应激损伤有关。     

ASS对实验性Ⅱ型糖尿病大鼠胰岛素和C肽分泌作用研究

目的 研究刺五加叶皂甙（ASS）对实验性Ⅱ型糖尿病大鼠胰岛素和C肽分泌作用影响。方法 应用放射免疫学方法对正常组和Ⅱ型糖尿病模型组大鼠（尾静脉注射链尿佐菌素25mg/kg加高脂，高热、高能量喂养）。在给予ASS后其空腹及口服葡萄糖后血浆中胰岛素和C肽变化测定。结果 ASS可增强Ⅱ型糖尿病大鼠胰岛素和C肽分泌，对正常大鼠无影响。结论 ASS可以促进Ⅱ型糖尿病大鼠胰岛素和C肽分泌。     

Effect of ovarian suppression on glucose metabolism of young lean women with and without ovarian hyperandrogenism

Gonadal steroids are believed to influence glucose metabolism, oestrogens inducing an improvement and androgens or progestins a deterioration. At baseline and after 3 months of ovarian suppression with a gonadotrophin-releasing hormone analogue (GnRHa: goserelin depot 3.75 mg/28 days), glucose metabolism was evaluated in eight lean women affected by ovarian hyperandrogenism (PCOS) and six age-weight-matched non-hyperandrogenic women (controls) by using both an oral glucose tolerance test (75 g; OGTT) and the minimal model method. The latter method allows calculation of peripheral insulin sensitivity (Si) and glucose dependent glucose utilization (Sg). In PCOS, higher fasting concentrations (P < 0.05) of insulin and C-peptide, and lower Sg (P < 0.05) and Si (P < 0.01) were found. GnRHa did not significantly modify glucose metabolism of controls, while in women with PCOS it decreased fasting glucose (P < 0.05) and significantly increased Si (P < 0.03) up to control values. The present data indicate that strong suppression of ovarian activity improves Si in lean women with PCOS, while it is without relevant effects on glucose metabolism of non-hyperandrogenic women.     

消渴汤方剂对Ⅱ型糖尿病大鼠胰岛素和C肽分泌的影响

目的　研究消渴汤中药对Ⅱ型糖尿病大鼠胰岛素和C肽水平分泌作用影响。方法　同随机方法将 4 4只Wistar大鼠分为正常和实验组 ,应用放射免疫方法对正常组和Ⅱ型糖悄病模型组大鼠 (尾静脉注射链尿佐菌素 2 5mg/kg加高脂 ,高热 ,高能量喂养 )。在给予消渴汤后其空腹及口服葡萄糖后血浆中胰岛素和C肽水平变化测定。结果　消渴汤可增强Ⅱ型糖尿病大鼠胰岛素和C肽分泌 ,对正常大鼠无影响。结论　消渴汤可以促进Ⅱ型糖尿病大鼠胰岛素和C肽分泌。     

厄洛替尼减轻STZ诱导的糖尿病肾病模型大鼠的肾损伤

目的:研究表皮生长因子受体(EGFR)抑制剂厄洛替尼(erlotinib)对糖尿病肾病大鼠肾脏的保护作用及机制。方法:采用大剂量(55 mg/kg)链脲佐菌素(STZ)腹腔注射诱导大鼠糖尿病肾病模型,以1周后血糖值16.7 mmol/L的大鼠为造模成功的标准。将糖尿病大鼠随机分为2组[STZ组和STZ+erlotinib(100 mg·kg~(-1)·d~(-1))组],并以正常大鼠为对照组(control组)。Erlotinib处理4周后,检测大鼠空腹血糖、血清肌酐和24 h尿蛋白含量的变化;HE染色和Masson染色观察肾脏组织病理学改变;Western blot检测各组肾脏组织中EGFR、p-EGFR、转化生长因子β1(TGFβ1)、Smad2/3、p-Smad2/3、Ⅳ型胶原蛋白(ColⅣ)和纤连蛋白(fibronectin)的蛋白水平;活性氧簇(ROS)和丙二醛(MDA)试剂盒分别检测各组肾脏组织中ROS和MDA水平。结果:与control组相比,STZ组血糖、24 h尿蛋白和血清肌酐水平均显著升高(P0.01),肾组织形态学出现异常变化;与STZ组相比,STZ+erlotinib组的血糖、24 h尿蛋白水平和血清肌酐水平显著降低(P0.05),肾小球结构恢复正常,肾小球系膜细胞增生程度明显减弱。厄洛替尼明显抑制了STZ大鼠肾组织中p-EGFR、TGFβ1、p-Smad2/3、ColⅣ和fibronectin蛋白水平,也明显抑制了STZ大鼠肾组织中ROS和MDA水平。结论:厄洛替尼可能通过抑制EGFR/TGFβ1-Smad2/3信号通路的激活来抑制糖尿病肾病肾组织的纤维化和氧化应激反应,从而减轻肾损伤。     

核黄素对STZ诱导的大鼠糖尿病肾病的治疗作用

目的:探讨核黄素对STZ诱导的大鼠糖尿病肾病的治疗作用及机制。方法:将雄性Sprague-Daw-ley大鼠随机分为3组,即正常对照组、糖尿病模型组、核黄素治疗组,采用腹腔注射链脲佐菌素法建立糖尿病大鼠模型,收集各组血、尿及肾组织,生化方法检测24h尿蛋白量、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)的活性及丙二醛(MDA)的含量,并计算肾脏脏器系数(KW/BW);Western blotting检测不同组别肾皮质TGF-β1、纤溶酶原活化抑制因子-1(PAI-1)蛋白质水平;光镜观察肾组织形态改变。结果:与糖尿病模型组大鼠比较,核黄素治疗组大鼠尿蛋白量显著降低(P0.01),肾组织及血清SOD、CAT活性升高(P0.01),肾组织MDA含量显著降低(P0.01),核黄素治疗组肾皮质TGF-β1及PAI-1蛋白表达明显低于糖尿病模型组。结论:核黄素对STZ诱导的糖尿病大鼠肾脏有一定的保护作用,其机制可能与其降低肾组织TGF-β1、PAI-1蛋白表达有关。     

Acute exercise reverses TRB3 expression in the skeletal muscle and ameliorates whole body insulin sensitivity in diabetic mice

Aim: TRB3 became of major interest in diabetes research when it was shown to interact with and inhibit the activity of Akt. Conversely, physical exercise has been linked to improved glucose homeostasis. Thus, the current study was designed to investigate the effects of acute exercise on TRB3 expression and whole body insulin sensitivity in obese diabetic mice. Methods: Male leptin-deficient (ob/ob) mice swam for two 3-h-long bouts, separated by a 45-min rest period. After the second bout of exercise, food was withdrawn 6 h before antibody analysis. Eight hours after the exercise protocol, the mice were submitted to an insulin tolerance test (ITT). Gastrocnemius muscle samples were evaluated for insulin receptor (IR) and IRS-1 tyrosine phosphorylation, Akt serine phosphorylation, TRB3/Akt association and membrane GLUT4 expression. Results: Western blot analysis showed that TRB3 expression was reduced in the gastrocnemius of leptin-deficient (ob/ob) mice submitted to exercise when compared with respective ob/ob mice at rest. In parallel, there was an increase in the insulin-signalling pathway in skeletal muscle from leptin-deficient mice after exercise. Furthermore, the GLUT4 membrane expression was increased in the muscle after the exercise protocol. Finally, a single session of exercise improved the glucose disappearance (K_ITT) rate in ob/ob mice. Conclusion: Our results demonstrate that acute exercise reverses TRB3 expression and insulin signalling restoration in muscle. Thus, these results provide new insights into the mechanism by which physical activity ameliorates whole body insulin sensitivity in type 2 diabetes.     

不同运动强度干预2型糖尿病模型大鼠的内脂素及糖代谢变化

文题释义：运动强度：指单位时间移动的距离或速度,或肌肉单位时间所做的功。2型糖尿病：由于胰岛β细胞分泌胰岛素不足或靶细胞对胰岛素不敏感所致,亦称非胰岛素依赖型糖尿病。背景：内脂素具有胰岛素样的降糖作用,在2型糖尿病的治疗中可能有着积极的意义,不同运动强度对其的影响也不同。目的：观察6周不同强度有氧运动干预2型糖尿病大鼠糖代谢的效应及内脂素变化的特点并探讨其关系。方法：采用高脂饲料喂养并注射链脲佐菌素的方法,建立雄性SD大鼠2型糖尿病模型,将造模成功的43只大鼠随机分为糖尿病安静对照组10只,糖尿病运动Ⅰ,Ⅱ,Ⅲ组各11只。此3个运动组大鼠运动强度分别为10,15,20 m/min,运动量均为1 h/d,每周5 d,持续运动6周后采集血样,检测糖代谢相关指标、血清及内脏脂肪内脂素水平。结果与结论：①实验中3个运动组糖代谢相关指标(空腹血糖、糖化血清蛋白、胰岛素及胰岛素抵抗指数等)均出现了改善,同时糖尿病运动Ⅰ,Ⅱ组血清内脂素水平均出现非常显著性降低(P < 0.01),而糖尿病运动Ⅲ组虽有一定程度下降,但无显著性意义(P > 0.05);②糖尿病运动Ⅰ,Ⅱ,Ⅲ组内脏脂肪内脂素水平出现了显著性下降(P < 0.05),其中糖尿病运动Ⅱ内脏脂肪内脂素下降最显著(P < 0.01);③结果证实,中、低强度有氧运动能更有效改善2型糖尿病大鼠胰岛素抵抗状态,降低血糖浓度,且与内脏脂肪减少和内脂素分泌减少有关,内脂素可能起了积极的作用。ORCID: 0000-0001-9865-1802(李颖)中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

沉默微小RNA-218表达保护STZ诱导的糖尿病大鼠肾组织

目的:探讨沉默微小RNA-218(microRNA-218,miR-218)表达对链脲佐菌素(streptozotocin,STZ)诱导的糖尿病肾病大鼠肾脏组织的保护作用及其可能机制。方法:采用单次腹腔注射STZ(50 mg/kg)方法制备糖尿病大鼠模型并构建miR-218短发夹RNA(short hairpin RNA,shRNA)慢病毒载体。SD大鼠被随机分为健康对照组、糖尿病模型组、空载慢病毒组及miR-218-shRNA组。于自动生化仪上检测不同时点(4、8和12周)大鼠血糖、24h尿蛋白量、血清肌酐(serum creatinine,SCr)及血尿素氮(blood urea nitrogen,BUN)含量。实时荧光定量PCR(RTqPCR)检测肾脏组织miR-218的表达。RT-qPCR和Western blot检测血红素氧合酶1(heme oxygenase-1,HO-1)、肾病蛋白(nephrin)和p38丝裂原激活的蛋白激酶(p38 mitogen-activated protein kinase,p38 MAPK)的mRNA及蛋白表达水平。Caspase-3活性检测试剂盒检测caspase-3活性。末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling,TUNEL)法检测肾脏组织细胞凋亡。结果:与健康对照组相比,STZ处理后大鼠miR-218表达水平显著升高。同时模型大鼠的血糖、24 h尿蛋白量、SCr及BUN含量显著升高(P0.05);模型大鼠肾脏组织中HO-1和nephrin的mRNA和蛋白表达水平显著降低,而p38 MAPK蛋白的磷酸化水平显著升高;另外,模型大鼠肾脏组织中的caspase-3活性也显著升高。模型大鼠感染miR-218-shRNA后,miR-218表达水平显著下降并可以显著逆转上述效应。miR-218-shRNA组肾脏组织细胞的凋亡水平显著低于糖尿病模型组及空载慢病毒组。结论:miR-218参与了糖尿病大鼠的肾脏损伤,慢病毒载体沉默其表达能有效抑制肾脏组织细胞的凋亡,提示miR-218可以作为糖尿病肾病的基因治疗靶点。     

Effect of the new somatostatin analogue SMS 201-995 on exogenously used insulin

Somatostatin and somatostatin analogues are inhibitors of insulin,glucagon, and growth hormone secretion. However, it has not been determined whether it is somatostatin or its analogues which affect these hormones when used concomitantly. The effect of the somatostatin analogue SMS 201-995 on exogenously infused insulin was observed in ten healthy volunteers. The study was carried out on two occasions with at least a 1-week interval. Each subject was infused with saline throughout the study and insulin at a rate of 40 mU/kg per hour between 60–160 min of the study (step A) or SMS 201-995 in a 75 g IV bolus following at a rate of 75 g/h for 160 min and insulin at the same rate and duration (step B). Hyper-insulinemia and SMS 201-995 significantly suppressed C-peptide secretion, but the degree of C-peptide suppression was greater in the SMS 201-995 infused step than in the insulin-only infused step. Blood glucose levels decreased markedly throughout the infusion of insulin with or without SMS 201-995. In step B, the decrease in blood glucose was greater than in step A. Insulin levels in step B increased to higher levels than in step A (from 81.1 ± 7.7 to 363.9 ± 22.7 mmol/l and from 82.7 ± 8.6 to 229.0 ± 23.4 mmol/l, respectively). These results show that SMS 201-995 increases the level of exogenously infused insulin. This is probably due to the impaired clearance of exogenous insulin. Correspondence to: M. Bayraktar     

21-氨基类固醇对脑冷冻伤大鼠局部脑葡萄糖利用率的影响

21-氨基类固醇是新发现的铁依类脂质过氧化作用的抑制剂。其中以U74006 F(U6F)的抗中枢神经损伤作用最佳。本实验使用~(14)C-脱氧葡萄糖放射自显影方法测定U6F对大鼠脑冷冻伤后局部脑葡萄糖利用率(LCGU)的影响。动物分三组,A组(n=10)正常对照;B组(n=11)冷冻伤;C组(n=9)U6F+冷冻伤。C组动物在冷冻伤前30分钟给予U6F 20mg/kg/日,分二次ip,共注射7次。冷冻伤后72小时断头处死动物。结果,冷冻伤组冻伤侧大脑皮质区平均LCGU为正常组的58±4%,而U6F预处理组为正常组的82±5%(P<0.01)。结果提示,U6F预处理能减轻冷冻伤对大鼠大脑皮质LCGU的抑制。     

罗格列酮对2型糖尿病心肌能量底物代谢的影响

目的：探讨在2型糖尿病中胰岛素抵抗(IR)对心肌能量底物代谢以及心功能的影响。 方法： 采用高脂喂养(40％脂肪、42％碳水化合物和18％蛋白)4周及链脲佐菌素(STZ，35 mg/kg)1次性腹腔注射建立2型糖尿病大鼠模型，成模后随机分为2组：实验对照组(fat-fed/STZ)继续高脂喂养，实验治疗组(fat-fed/STZ/RSG)给予罗格列酮(RSG) 3 mg·kg-1·d-1治疗2周；正常对照组(chow-fed)为普通饮食喂养(12％脂肪、60％碳水化合物和28％蛋白)。左室插管检测心功能后进行30 min等容离体心脏灌注，灌注液含100 μU胰岛素、3％BSA、5 mmol/L葡萄糖、0.4 mmol/L［3H］软脂酸，测定样品葡萄糖摄取量及［3H2O］计数，评估葡萄糖和脂肪酸氧化率。 结果： 高脂喂养加小剂量STZ所制备模型鼠的血糖、血浆胰岛素及FFA水平均高于正常鼠,与临床2型糖尿病的代谢特征相似。成模2周后，fat-fed/STZ组大鼠与chow-fed组比较，30 min心肌葡萄糖总氧化量明显减少［(54.7±6.2 vs 69.0±5.7)μmol/g干重，P<0.01］。葡萄糖氧化率由25％降至18％，脂肪酸氧化率由75％增加到82％；同时，心功能检查显示左室EDP明显增加［(14.3±1.8 vs 10.5±1.1) mmHg，P<0.05］，-dp/dtmax降低［(550±57 vs 650±42) mmHg/s，P<0.01］，而+dp/dtmax无明显改变。与fat-fed/STZ组比较，fat-fed/STZ/RSG组大鼠的血糖明显改善［(9.0±4.6 vs 15.1±3.3) mmol/L，P<0.01］，血浆胰岛素减少(P<0.05)，FFA降低［(2.2±0.8 vs 3.3±0.8) mmol/L, P<0.05］；心肌葡萄糖的总氧化量升高到(63.5±6.4)μmol/g。干重，葡萄糖和脂肪酸的氧化率分别为24％和76％，基本达到chow-fed组水平(P>0.05)；EDP和-dp/dtmax均得到明显的改善(P<0.05)。 结论： IR导致2型糖尿病心肌能量底物代谢的异常和左室舒张功能的降低，早期使用RSG改善IR，不仅能提高心肌对葡萄糖的利用、降低脂肪酸氧化，也有助于改善心功能。     

Parameters measuring beta-cell function are only valuable in diabetic subjects with low body mass index, high blood glucose level, or long-standing diabetes

Purpose

The aim of this study was to identify the most precise and clinically practicable parameters that predict future oral hypoglycemic agent (OHA) failure in patients with type 2 diabetes, and to determine whether these parameters are valuable in various subgroups.

Materials and Methods

We took fasting blood samples from 231 patients for laboratory data and standard breakfast tests for evaluation of pancreatic beta-cell function. Hemoglobin A1c (HbA1c) levels were tested, and we collected data related to hypoglycemic medications one year from the start date of the study.

Results

Fasting C-peptide, postprandial insulin and C-peptide, the difference between fasting and postprandial insulin, fasting beta-cell responsiveness (M0), postprandial beta-cell responsiveness (M1), and homeostasis model assessment-beta (HOMA-B) levels were significantly higher in those with OHA response than in those with OHA failure. The area under the curve (AUC) of the receiver operating characteristic (ROC) measured with postprandial C-peptide to predict future OHA failure was 0.720, and the predictive power for future OHA failure was the highest of the variable parameters. Fasting and postprandial C-peptide, M0, and M1 levels were the only differences between those with OHA response and those with OHA failure among diabetic subjects with low body mass index, high blood glucose level, or long-standing diabetes.

Conclusion

In conclusion, postprandial C-peptide was most useful in predicting future OHA failure in type 2 diabetic subjects. However, these parameters measuring beta-cell function are only valuable in diabetic subjects with low body mass index, high blood glucose level, or long-standing diabetes.     

胰岛素对糖尿病大鼠海马内神经营养因子-3阳性神经元表达的影响

目的：观察糖尿病大鼠海马中神经营养因子-3(NT-3)的表达变化及胰岛素治疗对其表达的影响。方法：将雄性大鼠随机分为对照组,糖尿病1,3月组,胰岛素治疗1,3月组,STZ 腹腔注射制模,测体重与血糖值并取海马行 HE 和免疫组化 SABC 法染色,计算机图像分析系统测平均光密度值。结果：血糖在糖尿病组比对照组显著升高;胰岛素组与对照组无显著性差异。海马各区 NT-3免疫阳性神经元的数量及阳性强度在糖尿病组有不同程度降低,以 CA1区最明显。胰岛素组则不降低。结论：糖尿病大鼠海马神经元 NT-3表达减弱,胰岛素治疗可使海马神经元 NT-3表达恢复正常。     

Protective effect of the daming capsule on impaired baroreflexes in STZ-induced diabetic rats with hyperlipoidemia

Background  

The Daming capsule (DMC) is a traditional Chinese medicine used to treat hyperlipoidemia. Both clinic trials and studies on animal models have demonstrated that DMC is beneficial against diabetic symptoms. Impairment of the baroreflex can cause life-threatening arrhythmias and sudden cardiac death in patients with diabetes mellitus (DM). This study was designed to elucidate the effects of DMC on baroreflexes in streptozocin (STZ)-induced diabetic rats with hyperlipoidemia.     

Effect of glucocorticoids on renal net glucose release in vivo in normal and diabetic rats

The effect of glucocorticoids on renal net glucose release in vivo in normal and diabetic rats was studied by the isotope-dilution method. Administration of hydrocortisone to normal fed rats increased renal net glucose release from 0.93 +/- 0.25 to 2.27 +/- 0.21 mg . dl-1 . min-1 and increased its contribution to blood glucose from 27.0 +/- 4.5 to 46.6 +/- 4.0%. The renal net glucose release and its contribution to blood glucose in adrenalectomized rats were 0.40 +/- 0.06 mg . dl-1 . min-1 and 16.3 +/- 1.4%, respectively, significantly less than those of normal control rats, and these parameters were raised to the levels of normal control rats by the administration of hydrocortisone. In rats with streptozotocin-induced diabetes, the renal net glucose release and its contribution to blood glucose were significantly increased to 2.22 +/- 0.51 mg . dl-1 . min-1 and 46.7 +/- 4.9%, respectively, and these parameters were normalized by adrenalectomy. These data indicate that glucocorticoids play an important role in regulation of renal net glucose release and its contribution to blood glucose in both normal and diabetic rats.     

UCH-L1在高糖刺激的足细胞及大鼠糖尿病肾病模型中的表达

目的探讨泛素羧基末端水解酶-1(ubiquitin carboxy-terminal hydrolase-1,UCH-L1)在高糖诱导的体外足细胞及糖尿病肾病大鼠模型体内足细胞中的表达。方法以25 mmol/L高糖刺激体外足细胞0、12、24 h后,提取细胞蛋白,采用Western bolt法检测UCH-L1的表达。20只8~10周龄Wistar大鼠,随机分为对照组和糖尿病肾病模型(STZ)组并造模,各10只,定期检测体重、血糖变化,处死大鼠取肾脏组织,HE染色和PAS染色观察肾脏形态学改变,采用免疫组化PV 9000两步法染色以WT1定位足细胞,检测足细胞内UCH-L1的表达。结果在不同时间高糖处理后,足细胞UCH-L1蛋白表达量随时间延长明显升高(P0.01);体重、血糖检测及HE、PAS染色证明糖尿病肾病模型构建成功,STZ组足细胞(WT1定位)内UCH-L1呈阳性,而对照组几乎无明显表达。结论分子生物学和形态学两种方法联合证明高糖可诱导体内外足细胞中UCH-L1的表达升高。