肝源性糖尿病患者胰岛β细胞功能和胰岛素抵抗及临床意义

目的探讨肝源性糖尿病患者胰岛β细胞功能和胰岛素抵抗的特征。方法对肝源性糖尿病(HD)26例,2型糖尿病(T2DM)30例,正常对照(NC)22例,行口服葡萄糖耐量试验,测定0 min、30 min、60 min、120 min、180 min血糖及胰岛素水平。计算稳态模式评估法的胰岛β细胞基础分泌指数(HOMA-β)、早相胰岛素分泌指数(△I30/△G30)、晚相胰岛素分泌指数(AUCI30-120/AUCG30-120),评估胰岛β细胞功能;计算空腹血糖与空腹胰岛素比值(PFG/FINS)、稳态模式评估法的胰岛抵抗指数(HOMA-IR)、肝脏胰岛素抵抗指数(HIR)及Matsuda指数(MSI),评估胰岛素抵抗。结果 HD组的HOMA-β和AUCI30-120/AUCG30-120高于T2DM组(P<0.05),与NC组无差异(P>0.05);HD组和T2DM组的△I30/△G30低于NC组(P<0.05),HD组和T2DM组无差异(P>0.05);HD组和NC组的PFG/FINS低于T2DM组(P<0.05),HD组和NC组的PFG/FINS和HOMA-IR无差异(P>0.05);HD组和T2DM组的HIR高于NC组(P<0.05),HD组和T2DM组无差异(P>0.05);HD组和T2DM组的MSI低于NC组(P<0.05),HD组和T2DM组无差异(P>0.05)。结论 HD患者基础胰岛素分泌接近正常人,以早相胰岛素分泌损害及餐后胰岛素抵抗为主。     

针刺提高2型糖尿病模型大鼠胰岛β细胞胰岛素的表达

背景:针刺治疗2型糖尿病具有很好的疗效。目的:观察针刺对2型糖尿病模型大鼠胰岛β细胞胰岛素表达的影响。方法:将糖尿病模型大鼠按随机化原则分为针刺组、西药组、模型组,同时设置正常对照组。针刺组大鼠取足三里、内庭和胰俞穴给予针刺治疗,西药组用罗格列酮0.2mg/kg灌胃,模型组用双蒸水2mL/kg灌胃,均1次/d,连续4周。结果与结论:①血糖:针刺组明显低于模型组、西药组(P<0.05)。②血脂:针刺组胆固醇和三酰甘油低于模型组(P<0.05);高密度脂蛋白胆固醇明显高于模型组(P<0.01)。针刺组三指标与西药组比较差异无显著性意义。③胰岛β细胞胰岛素表达:针刺组显著高于模型组和西药组(P<0.05)。④胰岛形态:模型组与西药组胰岛结构不完整,结构破坏,胰岛素染色效果差;针刺组胰岛结构趋向完整,胰岛素染色颗粒明显。说明针刺可显著提高2型糖尿病模型大鼠胰岛β细胞胰岛素表达水平,有效改善胰岛β细胞功能。     

肝X受体激动剂对db/db鼠肾脏肝X受体表达及其活性的影响

目的探讨肝X受体(LXR)激动剂T0901317对db/db小鼠肾脏肝X受体表达水平及其活性的影响。方法将8周龄雄性db/db小鼠分为db/db组和db/db+T0901317组(均n=7),同时以同龄同性别野生型C57BL/6小鼠为对照组(n=7)。对照组和db/db组小鼠胃饲生理盐水(50μl/只/天×7),db/db+T0901317组小鼠胃饲T0901317[12.5 mg/(kg·d)×7];4周后RT-PCR检测肾组织ABCA1 mRNA水平;Western blot检测上述各组小鼠肾组织LXRα、LXRβ蛋白表达水平。结果与对照组相比,db/db组LXRα蛋白表达量、ABCA1 mRNA表达水平明显下调(P0.05);与db/db组相比,db/db+T0901317组上述指标表达上调(P0.05);与db/db组相比,T0901317组LXRβ蛋白表达差异无统计学意义(P0.05),而对照组LXRβ蛋白下调(P0.05)。结论 LXR可能通过激活LXRα进而上调ABCA1以减轻糖尿病引起的肾脏炎症性损害,为拮抗糖尿病所致的肾脏炎症性损伤提供新的理论依据。     

长效胰岛素联合阿卡波糖在T2DM治疗中对血糖及胰岛β细胞的影响

目的 探讨长效胰岛素联合阿卡波糖治疗在2型糖尿病(T2DM)治疗中对血糖及胰岛β细胞的影响。方法回顾性分析2020年5月至2022年7月我院收治的60例T2DM患者临床资料,按照治疗方法不同分为观察组和对照组各30例。对照组采用长效胰岛素治疗,观察组在对照组基础上加用阿卡波糖治疗。比较两组临床疗效、血糖水平[餐后2 h血糖(2 hPG)、空腹血糖(FBG),糖化血红蛋白(HbA1c)]、胰岛素功能[胰岛素抵抗指数(HOMA-IR)和胰岛素分泌指数(HOMA-β)]及不良反应。结果 观察组治疗总有效率为93.33%,高于对照组的73.33%,差异有统计学意义(P<0.05);治疗后,观察组血糖水平均低于对照组,差异有统计学意义(P<0.05);治疗后,观察组HOMA-IR低于对照组,HOMA-IR高于对照组,差异有统计学意义(P<0.05);两组不良反应比较,差异无统计学意义(P>0.05)。结论采用长效胰岛素联合阿卡波糖治疗2型糖尿病患者,能够提高临床疗效,恢复胰岛功能,有效改善患者血糖水平,安全可靠,值得推广。     

重组人生长激素对糖尿病小鼠胰岛β细胞功能的保护作用机制分析

目的探讨重组人生长激素(rh GH)对糖尿病小鼠胰岛β细胞功能的影响,并对其可能存在的保护机制进行研究。方法选择30只小鼠采取高糖高脂饲养以及链脲佐菌素(35 mg/kg)建模2型糖尿病模型,采用随机数字表法均分为对照组、模型组、实验组。实验组小鼠采取皮下注射rh GH(0. 3 IU/kg),模型组及对照组小鼠注射等体积生理盐水,给药周期7 d。检测干预0 d、1 d、4 d、7 d时间点时各组小鼠血糖含量,酶联免疫法检测各组小鼠血清胰岛素、胰高血糖素、甘油三酯(TG)、总胆固醇(TC)水平以及胰岛组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSHPx)、丙二醛(MDA)水平以及肿瘤坏死因子-α(TNF-α)、白介素-6 (IL-6)水平。HE染色观察胰岛组织病理学变化,采用TUNEL法及RT-PCR分别检测胰岛β细胞凋亡及Bcl-2、Bax表达水平。结果在0 d、1 d、4 d、7 d时,模型组小鼠血糖含量均低于对照组(P 0. 05),且在1 d、4 d、7 d时实验组小鼠血糖水平均低于模型组(P 0. 05);模型组小鼠TG、TC、胰岛素及胰高血糖素均明显高于对照组(P 0. 05),且实验组小鼠血清胰岛素、胰高血糖素、TG与TC含量均低于模型组(P 0. 05);实验组小鼠胰岛组织中TNF-α、IL-6及MDA水平低于模型组(P 0. 05),而SOD、GSH-Px含量明显高于模型组(P 0. 05); HE染色结果显示模型组小鼠胰岛组织排列紊乱、细胞大小不均匀且炎性细胞浸润,实验组小鼠胰岛组织受损程度较模型组轻;实验组小鼠胰岛β细胞凋亡率低于模型组,RT-PCR结果显示实验组小鼠胰岛β细胞中的Bcl-2表达量高于模型组(P 0. 05)、Bax达量低于于模型组(P 0. 05)。结论 rh GH可以降低糖尿病小鼠血糖、血脂、胰岛素水平,降低胰岛β细胞凋亡率,可能与促进Bcl-2表达、抑制Bax表达量、减少氧化应激及炎性因子水平有关。     

2型糖尿病患者糖化血红蛋白水平与胰岛素分泌及胰岛素抵抗的关系

目的 比较不同糖化血红蛋白(HbA1c)水平的2型糖尿病(T2DM)患者胰岛素分泌和胰岛素抵抗情况,了解葡萄糖毒性对胰岛β细胞分泌功能的影响。方法 将137例T2DM患者,按HbA1c水平分为4组,即A组(HbA1c≤7%),B组(7%11%),测定各组空腹血糖(FPG),HbA1c及精氨酸刺激前后各时点的胰岛素(INS)。用稳态模型评估法评价基础胰岛素分泌功能(HOMA-β)和胰岛素抵抗指数(HOMA-IR),并用精氨酸刺激后血糖校正胰岛素增值(△INS/FPG)评估第一相胰岛素分泌功能。结果 各组T2DM患者FPG差异均有统计学意义(F=15.633～106.154,P值均<0.01),且与HbA1c呈正相关(r=0.627,P<0.01); HOMA-β和△INS/FPG均表现为A组、B组分别与其他各组差异有统计学意义(F=4.106～16.255,P值均<0.05),但C组与D组之间差异无统计学意义(F=0.761,2.756,P值均>0.05); A组HOMA-IR与C组、D组之间差异有统计学意义(F=4.836,8.524,P值均<0.05); 精氨酸刺激后胰岛素分泌不足检出率在HbA1c>9%时明显升高。结论 胰岛β细胞功能的判断受长期糖毒性的干扰,故将T2DM患者的HbA1c控制在9%以下进行胰岛素分泌功能评估及精氨酸刺激试验,能较为准确地反映胰岛β细胞功能。     

2型糖尿病患者血脂水平与糖化血红蛋白、胰岛素抵抗及胰岛β细胞功能的关系

目的:探讨2型糖尿病患者的血脂水平与其糖化血红蛋白水平、胰岛素抵抗情况及胰岛β细胞功能的关系。方法:入选2型糖尿病患者136例,分别以糖化血红蛋白10.0%、胰岛素抵抗指数2.8以及胰岛功能指数20为界值将其分为高糖化血红蛋白组(HH组,n=76)、低糖化血红蛋白组(LH组,n=60);胰岛素重抵抗组(IR组,n=65)、胰岛素轻抵抗组(SR组,n=71);胰岛β细胞功能轻减退组(BN组,n=74)和胰岛β细胞功能重减退组(BW组,n=62),分析各组的血脂水平。结果:HH组和LH组的三酰甘油(TG)和高密度脂蛋白(HDL)的水平均无显著差异(P>0.05),HH组的总胆固醇(TC)和低密度脂蛋白(LDL)的水平显著高于LH组(P<0.05);IR组的TG水平显著高于SR组(P<0.05);BW组的HDL水平显著高于BN组(P<0.05)。结论:2型糖尿病患者血糖越高、胰岛素抵抗越严重、胰岛β细胞功能越差,血脂紊乱越严重。     

2型糖尿病患者体质量指数、血脂与胰岛β细胞功能的相关性研究

目的探讨2型糖尿病(T2DM)患者体质量指数(BMI)、血脂与胰岛β细胞功能的相关性。方法选取2018年12月至2019年12月于该院内分泌科门诊就诊的334例T2DM患者作为研究对象,收集年龄、病程等基线资料,计算BMI,检测空腹血糖(FBG)、空腹胰岛素(FINS)、血清三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)及高密度脂蛋白胆固醇(HDL-C),计算胰岛β细胞功能指数(HOMA-β)、胰岛素敏感指数(HOMA-ISI)及胰岛素抵抗指数(HOMA-IR)。结果相关性分析显示,HOMA-IR与BMI呈正相关(P<0.05),HOM A-ISI与HDL-C呈正相关(P<0.05)。根据BMI将患者分为正常组、超重组和肥胖组,3组FBG、HOMA-IR差异有统计学意义(P<0.05);以HDL-C=1.1 mmol/L为界值将患者分为两组,两组年龄、病程、FINS、HOMA-ISI差异有统计学意义(P<0.05)。多元线性回归分析示,BMI是T2DM患者HOMA-IR的独立影响因素(P<0.05);HDL-C是T2DM患者HOMA-ISI的独立影响因素(P<0.05)。结论T2DM患者BMI、HDL-C与胰岛β细胞功能存在一定相关性,对T2DM合并胰岛素抵抗的诊断及指导治疗具有重要参考价值。     

2型糖尿病患者血清松弛素-2与胰岛β细胞功能的相关性研究

目的探讨2型糖尿病(T2DM)患者血清松弛素-2(RLX-2)的变化及其与胰岛β细胞功能的相关性,以及RLX-2作为评价胰岛β细胞功能的价值。方法前瞻性研究连续入选2015年1~9月因"胸痛"就诊于首都医科大学附属北京友谊医院的患者,按既往病史及入院葡萄糖粉糖耐量实验(OGTT)分为三组:A组(血糖正常组,指既往无糖尿病史且OGTT正常)71例,B组(糖尿病前期组,包括OGTT糖耐量受损和/或空腹血糖受损)68例,C组(2型糖尿病组,包括既往病史和入院OGTT证实的T2DM)133例。经更新稳态模型评估(HOMA2)计算β细胞功能、胰岛素敏感性和胰岛素抵抗指数。比较三组患者RLX-2及胰岛β细胞功能、实验室指标等参数的差异,并分析B组和C组患者中RLX-2与β细胞功能的相关性。结果三组患者比较,随着糖代谢异常程度增加,患者甘油三酯及hs-CRP水平逐渐升高,LVEF水平逐渐降低(P0.05)。随着糖代谢异常程度加重,空腹胰岛素及胰岛素抵抗指数显著升高,而胰岛β细胞功能及胰岛素敏感性均显著降低(P0.05)。三组患者RLX-2比较,B组患者RLX-2较A组及C组显著增加,差异具有统计学意义(P0.05);随着糖代谢异常进展,胰岛β细胞功能及胰岛素敏感性逐步下降,而胰岛素抵抗指数逐渐增加。多元逐步回归分析显示,T2DM患者血RLX-2水平与胰岛β细胞功能呈独立正相关,相关系数为0.439(P0.001)。结论血清RLX-2可能是糖代谢异常的一种早期血清标志物,它可能反映了胰岛β细胞的代偿功能。     

十二指肠空肠旁路术对2型糖尿病大鼠胰岛β细胞功能恢复的作用

目的:研究十二指肠空肠旁路手术(duodenal jejunal bypass sugery,DJB)对2型糖尿病(T2DM)大鼠胰岛β细胞功能恢复的影响。方法:采用高糖高脂饮食联合小剂量STZ腹腔注射建立T2DM动物模型,将成模大鼠随机分为T2DM组(T2DM-C)和T2DM手术组(T2DM-DJB),普通饮食大鼠为空白对照组(WC)。分别检测3组大鼠基础代谢指标、空腹血糖(FBG)、空腹血清胰岛素(FINS)和胰岛素抵抗指数(HOMAIR)。术后20周处死大鼠,留取胰腺组织放入4%多聚甲醛中固定。用HE染色、免疫荧光双标法和电镜检测胰岛病理学形态、胰岛β细胞和α细胞比例变化和胰岛超微结构。结果:术后T2DM-DJB组大鼠体重和饮食量较术前无明显改变,T2DM-DJB组与T2DM-C组比较血糖和胰岛素水平明显下降,胰岛素抵抗得到改善;术后HE染色示胰岛形态恢复良好;免疫荧光示胰岛β细胞所占胰岛比例较T2DM-C组升高;电镜示胰岛β细胞超微结构得到改善。结论:DJB手术改善T2DM大鼠葡萄糖代谢和胰岛素抵抗,缓解胰岛β细胞凋亡,改善胰岛β细胞功能。     

Antihyperglycemic and antioxidant properties of caffeic acid in db/db mice

This study investigated the blood glucose-lowering effect and antioxidant capacity of caffeic acid in C57BL/KsJ-db/db mice. Caffeic acid induced a significant reduction of the blood glucose and glycosylated hemoglobin levels than the control group. The plasma insulin, C-peptide, and leptin levels in caffeic acid group were significantly higher than those of the control group, whereas the plasma glucagon level was lower. Increased plasma insulin by caffeic acid was attributable to an antidegenerative effect on the islets. Caffeic acid also markedly increased glucokinase activity and its mRNA expression and glycogen content and simultaneously lowered glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities and their respective mRNA expressions, accompanied by a reduction in the glucose transporter 2 expression in the liver. In contrast to the hepatic glucose transporter 2, adipocyte glucose transporter 4 expression was greater than the control group. In addition, caffeic acid significantly increased superoxide dismutase, catalase, and glutathione peroxidase activities and their respective mRNA levels, while lowering the hydrogen peroxide and thiobarbituric acid reactive substances levels in the erythrocyte and liver of db/db mice. These results indicate that caffeic acid exhibits a significant potential as an antidiabetic agent by suppressing a progression of type 2 diabetic states that is suggested by an attenuation of hepatic glucose output and enhancement of adipocyte glucose uptake, insulin secretion, and antioxidant capacity.     

The dual peroxisome proliferator-activated receptor alpha/gamma activator muraglitazar prevents the natural progression of diabetes in db/db mice

There are two major defects in type 2 diabetes: 1) insulin resistance and 2) insulin deficiency due to loss of beta-cell function. Here we demonstrated that treatment with muraglitazar (a dual peroxisome proliferator-activated receptor alpha/gamma activator), when initiated before or after the onset of diabetes in mice, is effective against both defects. In study 1, prediabetic db/db mice were treated for 12 weeks. The control mice developed diabetes, as evidenced by hyperglycemia, hyperinsulinemia, reduced insulin levels in the pancreas, blunted insulin response to glucose, and impaired glucose tolerance. The muraglitazar-treated mice had normal plasma glucose, and insulin levels, equivalent or higher pancreatic insulin content than normal mice, showed a robust insulin response to glucose and exhibited greater glucose tolerance. In study 2, diabetic db/db mice were treated for 4 weeks. The control mice displayed increased glucose levels, severe loss of islets, and their isolated islets secreted reduced amounts of insulin in response to glucose and exendin-4 compared with baseline. In muraglitazar-treated mice, glucose levels were reduced to normal. These mice showed reduced loss of islets, and their isolated islets secreted insulin at levels comparable to baseline. Thus, muraglitazar treatment decreased both insulin resistance and preserved beta-cell function. As a result, muraglitazar treatment, when initiated before the onset of diabetes, prevented development of diabetes and, when initiated after the onset of diabetes, prevented worsening of diabetes in db/db mice.     

Glucagon-like peptide 1 receptor agonist ZP10A increases insulin mRNA expression and prevents diabetic progression in db/db mice

We characterized the novel, rationally designed peptide glucagon-like peptide 1 (GLP-1) receptor agonist H-HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPSK KKKKK-NH2 (ZP10A). Receptor binding studies demonstrated that the affinity of ZP10A for the human GLP-1 receptor was 4-fold greater than the affinity of GLP-1 (7-36) amide. ZP10A demonstrated dose-dependent improvement of glucose tolerance with an ED50 value of 0.02 nmol/kg i.p. in an oral glucose tolerance test (OGTT) in diabetic db/db mice. After 42 days of treatment, ZP10A dose-dependently (0, 1, 10, or 100 nmol/kg b.i.d.; n = 10/group), decreased glycosylated hemoglobin (HbA1C) from 8.4 +/- 0.4% (vehicle) to a minimum of 6.2 +/- 0.3% (100 nmol/kg b.i.d.; p < 0.05 versus vehicle) in db/db mice. Fasting blood glucose (FBG), glucose tolerance after an OGTT, and HbA1C levels were significantly improved in mice treated with ZP10A for 90 days compared with vehicle-treated controls. Interestingly, these effects were preserved 40 days after drug cessation in db/db mice treated with ZP10A only during the first 50 days of the study. Real-time polymerase chain reaction measurements demonstrated that the antidiabetic effect of early therapy with ZP10A was associated with an increased pancreatic insulin mRNA expression relative to vehicle-treated mice. In conclusion, long-term treatment of diabetic db/db mice with ZP10A resulted in a dose-dependent improvement of FBG, glucose tolerance, and blood glucose control. Our data suggest that ZP10A preserves beta-cell function. ZP10A is considered one of the most promising new drug candidates for preventive and therapeutic intervention in type 2 diabetes.     

MicroRNA-29b Inhibits Diabetic Nephropathy in db/db Mice

Inflammation and its consequent fibrosis are two main features of diabetic nephropathy (DN), but target therapy on these processes for DN remains yet ineffective. We report here that miR-29b is a novel therapeutic agent capable of inhibiting progressive renal inflammation and fibrosis in type 2 diabetes in db/db mice. Under diabetic conditions, miR-29b was largely downregulated in response to advanced glycation end (AGE) product, which was associated with upregulation of collagen matrix in mesangial cells via the transforming growth factor-β (TGF-β)/Smad3-dependent mechanism. These pathological changes were reversed by overexpressing miR-29b, but enhanced by knocking-down miR-29b. Similarly, loss of renal miR-29b was associated with progressive diabetic kidney injury, including microalbuminuria, renal fibrosis, and inflammation. Restored renal miR-29b by the ultrasound-based gene therapy was capable of attenuating diabetic kidney disease. Further studies revealed that inhibition of Sp1 expression, TGF-β/Smad3-dependent renal fibrosis, NF-κB–driven renal inflammation, and T-bet/Th1-mediated immune response may be mechanisms associated with miR-29b treatment in db/db mice. In conclusion, miR-29b may play a protective role in diabetic kidney disease and may have therapeutic potential for diabetic kidney complication.     

The loss of GLUT2 expression by glucose-unresponsive beta cells of db/db mice is reversible and is induced by the diabetic environment.

Glucose-induced insulin secretion by beta cells of diabetic db/db mice was studied by a pancreas perfusion technique, and the levels of GLUT2 protein in pancreatic islets were assessed by immunofluorescence microscopy and protein blot analysis. Beta cells from diabetic mice had a high basal rate of insulin secretion; they did not respond to glucose stimulation but displayed a normal secretory response to arginine. At the same time, GLUT2 expression by db/db islets was lost whereas beta cells from nondiabetic db/+ mice expressed high levels of this transporter. GLUT2 levels in liver or kidney of diabetic mice were, however, mostly unaltered. Transplanting islets from db/db mice under the kidney capsule of db/+ mice restored normal GLUT2 levels. Conversely, transplantation of db/+ islets into db/db mice induced the disappearance of GLUT2 expression. When islets from db/+ mice were transplanted under the kidney capsule of streptozocin-diabetic mice, the immunodetection of GLUT2 also disappeared. We conclude that: (a) GLUT2 expression is decreased in glucose-unresponsive beta cells from db/db mice; (b) the decreased expression of GLUT2 is reversible; (c) the loss of GLUT2 expression is induced by the diabetic environment of db/db and streptozocin-induced diabetic mice. These observations together with previously published data suggest that a factor different from glucose or insulin regulates the beta cell expression of GLUT2.     

2型糖尿病患者血清网膜素-1水平与肾损伤程度关系的研究

目的 探讨血清网膜素-1(serum omentin-1)水平与2型糖尿病(T2DM)肾病发病的关系。方法 将100例2型糖尿病肾病患者按糖尿病肾病(diabetic nephropathy,DN)诊断标准分为DM组(44例)与DN组(56例)。按照Mogenson分期将DN组分为DN早期(DN1)30例,DN晚期(DN2)26例。另择80例健康体检者作为正常对照组(NC)。同时检测糖化血红蛋白(HbA1c)、肌酐(Scr)、尿素氮(BUN)、β2微球蛋白(β2-MG)、胰岛素抵抗指数(HOMA-IR)和血清网膜素-1,进行相关的统计学分析。结果DM,DN和NC组HbA1c,Scr,BUN,β2-MG,HOMA-IR和血清网膜素-1指标差异均有统计学意义(F=6.078～16.231,均P<0.05)。其中DM组和NC组间除了HbA1c和HOMA-IR以外,其它检测指标相比差异均无统计学意义(t=1.421～2.637,均P>0.05),而DN组与NC组上述六项指标相比差异均有统计学意义(t=8.981～26.785,均P<0.05)。DN组和DM组间检测指标差异均有统计学意义(t=6.371～21.673,均P<0.05)。DN1组和DN2组间HbA1c,Scr,BUN和β2-MG差异均无统计学意义(t=0.981～1.389,均P>0.05)。而DN2组HOMA-IR水平明显比DN1组高,而血清网膜素-1水平明显比DN1组低,两组差异均有统计学意义(t=68.451～76.814,均P<0.01)。DN组HOMA-IR水平与血清网膜素-1指标呈显著负相关(r=-0.405,P<0.05)。结论 血清网膜素-1与胰岛素抵抗关系密切,血清网膜素-1可能是2型糖尿病患者肾脏损伤程度的靶标。     

血清甲状腺激素水平与2型糖尿病小鼠视网膜病变的发生和进展研究

目的研究血清甲状腺激素水平与2型糖尿病小鼠视网膜病变的发生和进展的关系。方法选取健康C57BL小鼠作为对照(对照组),db/db小鼠为2型糖尿病模型(2型糖尿病组),db/db小鼠腹腔注射甲状腺素(T4)稀释液以建立2型糖尿病甲状腺功能亢进小鼠(2型糖尿病甲亢组),db/db小鼠以甲巯咪唑替代饮水建立2型糖尿病甲状腺功能减退小鼠(2型糖尿病甲减组)。2型糖尿病甲亢和2型糖尿病甲减模型建立6个月后,酶联免疫吸附试验(ELISA)法测定小鼠血清空腹血糖(FBG)、餐后2 h血糖(2 h PG)、空腹胰岛素(FINS)、血清总三碘甲腺原氨酸(T3)、血清T4及促甲状腺激素(TSH)水平;电生理仪检测小鼠视觉电生理指标和TUNEL法检测小鼠视网膜神经节细胞(RGCs)凋亡率。结果与对照组相比,2型糖尿病组、2型糖尿病甲亢和2型糖尿病甲减组FBG、2 h PG和FINS均显著升高,差异均有统计学意义(P<0.05);但T2甲亢组或T2甲减组与2型糖尿病组相比差异均无统计学意义(P>0.05)。与2型糖尿病组相比,2型糖尿病甲亢组血清鼠T3、T4及视觉a波峰潜时均显著升高,血清TSH及a波峰振幅显著降低,差异均有统计学意义(P<0.05);与2型糖尿病组相比,2型糖尿病甲减组血清鼠T3、T4均显著降低,血清TSH显著升高,差异均有统计学意义(P<0.05),视觉a波峰潜时和a波峰振幅差异均无统计学意义(P>0.05)。2型糖尿病、2型糖尿病甲亢和2型糖尿病甲减组小鼠视网膜病变发生率和RGCs凋亡率均高于对照组,差异均有统计学意义(P<0.05),2型糖尿病甲亢组小鼠视网膜病变发生率和RGCs凋亡率均高于2型糖尿病组小鼠,差异均有统计学意义(P<0.05),2型糖尿病甲减组小鼠与2型糖尿病组小鼠视网膜病变发生率和RGCs凋亡率差异均无统计学意义(P>0.05)。结论血清甲状腺激素水平增加可引起2型糖尿病小鼠视网膜病变的发生,并且可导致其病变程度的进一步增加,而血清甲状腺激素水平降低则对2型糖尿病小鼠视网膜病变及进展无显著影响。     

TGF-β／Smad阻遏子c-Ski与糖尿病肾病的相关性研究

目的探讨阻遏子c—Ski对TGF-β／Smad信号途径的抑制作用与糖尿病肾病（diabetic nephropathy,DN）的关系。方法将所有大鼠随机分为正常对照组（NC组）、糖尿病（diabetes mellitus,DM）模型组（DM组）和吡格列酮干预组（PT组）。尾静脉小剂量注射链脲佐菌素建立DM大鼠模型。在实验期间连续监测血糖,8w末处死动物并采集血尿标本用于相关的生化指标测定,采用real—timePCR方法检测TGF-β和c—Ski的mRNA水平,免疫组化法检测TGF—β1和c—Ski蛋白表达情况,并进行统计学分析。结果与NC组相比,DM组血糖和血尿素氮（blood urea nitrogen,BUN）、24h尿微量白蛋白（24 hours urinary microalbumin,24hUMA）水平明显升高,经PT干预后大鼠血糖、BUN、24hUMA水平较DM组均显著下降,差异均有统计学意义（P均〈0．05）。PCR结果显示,DM组的TGF-β1mRNA水平较NC组显著升高,经PT干预后,其表达量显著降低,差异均有统计学意义（P均〈0．05）,而c—SkimRNA水平三组间差异无统计学意义（P〉0．05）。与NC组比较,DM组肾组织病理形态呈阳性表达,而PT组与NC组相近。免疫组化结果显示TGF-β1表达量在DM组较NC组显著增加,但c—Ski蛋白表达低于NC组,经盯干预后TGF-β1表达较DM组下降,而c—Ski表达显著增加,差异均有统计学意义（P均〈0．05）。结论DN中阻遏子c—Ski表达的下调减少了对TGF-β／Smad途径的阻断作用,而PPAR-γ可减少这种下调,为DN治疗机制的研究提供新的实验依据。     

2型糖尿病肾病患者检测血清基质金属蛋白酶-10的意义

目的 探讨血清基质金属蛋白酶-10(MMP-10)水平与2型糖尿病肾病发病的关系。方法 将100例2型糖尿病肾病患者按糖尿病肾病(DN)诊断标准分为糖尿病无肾病(DM)组(42例)与DN组(58例)。按照Mogenson分期将DN组分为DN早期(DN1)30例,DN晚期(DN2)28例。另择60例健康体检者作为正常对照(NC)组。同时检测糖化血红蛋白(HbA1c)、肌酐(Scr)、尿素氮(BUN)、24 h尿微量清蛋白排泄率(UAER)、β₂微球蛋白(β₂-MG)和MMP-10,进行相关的统计学分析。结果 DM,DN和NC组HbA1c,Scr,UAER,BUN,β₂-MG和MMP-10指标差异有统计学意义(F=6.478～10.892,均P<0.05)。DM组和NC组间除HbA1c外其它检测指标差异均无统计学意义(t=1.421～2.637,均P>0.05),而DN组与NC组比较差异均有统计学意义(t=8.451～26.678,均P<0.05)。DN组和DM组间除HbA1c外其它检测指标差异均有统计学意义(t=6.371～21.673,均P<0.05)。DN1组和DN2组间HbA1c,Scr,UAER,BUN和β₂-MG差异无统计学意义(t=0.891～1.385,均P>0.05)。而DN2组MMP-10水平明显比DN1组高,两组差异有统计学意义(t=86.371,P<0.01)。结论 血清MMP-10水平可能是2型糖尿病肾病患者肾脏损伤程度的靶标。     

马来酸罗格列酮对2型糖尿病患者颈动脉内膜中层厚度的影响

目的观察在2型糖尿病(T2DM)的患者中应用马来酸罗格列酮治疗对其颈总动脉内膜中层厚度(IMT)的影响。方法T2DM患者(T2DM组)与糖耐量正常者(NGT组)各30例分别检测空腹血糖(FPG)、血胰岛素(FIns)、糖基化血红蛋白(HbA1c),计算胰岛素抵抗指数(HOMA-IR),同时测定超敏C反应蛋白(hsCRP),并应用超声仪测定IMT,然后T2DM组接受马来酸罗格列酮治疗12个月后再次检测上述指标,比较各指标的变化。结果T2DM组的FPG、FIns、HbA1c、HOMA-IR、hsCRP和IMT均显著高于NGT组(P<0.05或P<0.01);马来酸罗格列酮治疗后IGT组的上述指标与治疗前相比均显著下降(P<0.05或P<0.01)。结论马来酸罗格列酮治疗可改善T2DM患者胰岛素抵抗状态,降低炎症反应,并可能缓解动脉粥样硬化的发生和发展。