2型糖尿病大鼠模型的建立

目的 探讨2型糖尿病动物模型建立的方法.方法 根据体重将35只Wistar大鼠随机分为对照组(10只)和糖尿病组(25只);糖尿病组喂高糖高脂饲料,对照组喂普通饲料,喂养1个月后,糖尿病组大鼠一次性腹腔注射链脲佐菌素(STZ) 25 mg/kg.bw,对照组注射相同剂量柠檬酸钠缓冲液,72 h后以随机血糖≥16.7 mmol/L确定为糖尿病模型.结果 STZ注射后72 h,与对照组相比糖尿病组大鼠血糖明显升高(P＜0.05),葡萄糖耐量,胰岛素耐受均异常,血清TG,TC,LDL-C显著升高(P＜0.05),同时伴有多饮、多食、多尿等糖尿病症状.结论 高糖高脂饲料联合小剂量腹腔注射STZ可致大鼠血糖明显上升,血脂紊乱等2型糖尿病症状.     

链脲佐菌素注射剂量对建立2型糖尿病大鼠模型的影响

目的探讨不同链脲佐菌素(STZ)注射剂量和方法对大鼠血糖值、血糖稳定性和胰岛损害的影响。方法75只SPF级6周龄雄性Wistar大鼠高脂高糖、饲养8周后,分别给予20、25、30mg/kg的STZ腹腔注射。造模后连续7周每周观察各组大鼠的体重、空腹血糖和餐后2h血糖。评价各组大鼠血糖变化和成模率。实验结束时测定血清胰岛素(INS)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)等。HE染色和胰岛素免疫组化观察胰岛细胞形态学特点。结果20mg/kg注射组成模率较低(30%);25mg/kg注射组成模率较高(73.3%),血糖中度升高并且稳定,胰岛结构完整,β细胞数量和细胞质内棕色颗粒有所减少;30mg/kg的STZ注射组血糖较高,死亡率较高,并且胰岛和β细胞数量极少,小胰岛多见,形状不规则,出现空泡样变性。结论高脂、高糖饲养8周后联合小剂量STZ25mg/kg能够造成更具有代表人类2型糖尿病病理生理特征的大鼠模型。     

HGF在2型糖尿病大鼠视网膜病变中的变化及意义

目的探讨肝细胞生长因子(Hepatocyte Growth Factor HGF)在糖尿病视网膜病变(Diabetic Retinopathy,DR)发生发展中的作用。方法雄性Wistar大鼠70只,随机分为实验组和对照组:实验组大鼠40只,喂以高糖高脂饲料2月后,腹腔注射链脲佐菌素(STZ)30 mg/kg;对照组大鼠30只,喂以普通饲料2月后,腹腔注射等体积的枸橼酸缓冲液。两组分别于注射前、注射后1月、2月、3月和6月每组各处死6只,取血测定血清HGF、胰岛素水平,并制备视网膜病理及电镜切片。结果实验组大鼠血HGF于注射STZ 1月后即明显增高,至2月时达最高值,以后逐渐降低,但始终高于对照组(P<0.01)。结论实验组大鼠血清HGF水平显著高于对照组,提示HGF可能参与了DR的发生发展。     

褪黑素改善高糖高脂饲养大鼠胰岛素敏感性

目的:观察褪黑素对高糖高脂饲养大鼠胰岛素敏感性的影响。方法:将18只雄性SD大鼠(150~200g)随机分为正常组(CD组)与高糖高脂组(HFSD组),分别饲以正常饲料与高糖高脂饲料(53%基础饲料含蔗糖37%和猪油10%)喂养6个月后,给药治疗2个月;治疗期间,给褪黑素组(Mel组)每天腹腔注射药物褪黑素(Melatonin,Mel,4 mg/kg),对照组腹腔注射生理盐水。测定空腹血糖、胰岛素、甘油三酯(TG)、游离脂肪酸(FFA)、高密度脂蛋白胆固醇(HDL—C)水平,做口服葡萄糖耐量实验(OGTT)和胰岛素敏感性实验。结果:高糖高脂饮食可诱导SD大鼠产生胰岛素抵抗,引起SD大鼠空腹血糖、血清胰岛素、TG、FFA水平升高;胰岛素敏感性、HDL—C水平下降。褪黑素治疗后,胰岛素敏感性增强,改善了胰岛素抵抗。结论:Mel能降低高糖高脂饲养SD大鼠糖脂状况,提高胰岛素敏感性,改善胰岛素抵抗。     

复方丹参滴丸对2型糖尿病大鼠肾组织HIF-1α及VEGF表达的影响

目的 观察复方丹参滴丸(DSP)防治2型糖尿病大鼠肾脏病变的效果并初步探讨其作用机理.方法 采用高糖高脂喂养结合腹腔注射2%链脲佐菌素(STZ,30 mg/kg)方法制备2型糖尿病模型大鼠.干预组经口灌服复方丹参滴丸[500mg/(kg·d),共8周].检测24 h尿微量白蛋白(24hUAlb)、空腹血糖(FBG)、空...     

卷柏对2型糖尿病大鼠模型葡萄糖代谢影响的实验研究

[目的]建立一种发病过程类似人类2型糖尿病的动物模型,并运用此模型评价卷柏不同溶剂提取对其降糖活性的影响. [方法]雄性SD大鼠高糖高脂饲料喂养4周后,以小剂量链脲佐菌素(STZ)诱发胰岛素代偿分泌障碍,使之产生高血糖症,观察卷柏不同溶剂提取物对糖尿病大鼠血糖、体重、摄食量、饮水量、胰岛素敏感性的影响.[结果]大鼠腹腔注射STZ 72 h后,血糖、TC、LDL-C、ALT、AST及BUN明显升高,血清HDL-C明显降低.给予卷柏不同溶剂提取物3周,卷柏醇提物组血糖、摄食量、饮水量比模型组明显降低,胰岛素敏感性明显升高;卷柏水提物组胰岛素敏感性也明显升高,血糖、摄食量明显降低,但饮水量变化不明显. [结论]通过高糖高脂饲料加小剂量STZ建立了2型糖尿病模型,可用于糖尿病治疗药物的筛选;卷柏醇提物降糖作用优于卷柏水提物.     

双歧杆菌对2型糖尿病模型大鼠干预效果观察

目的观察双歧杆菌微生态制剂对2型糖尿病模型大鼠糖代谢、脂代谢和肠道菌群结构的干预效果。方法实验大鼠按体重随机分为4组,空白对照组以基础饲料喂养,模型对照组、双歧杆菌低剂量组和高剂量组以高脂高糖饲料喂养,同时低、高剂量组每日灌胃给予双歧杆菌微生态制剂4和12 ml/(kg·d),6周后腹腔注射小剂量链脲佐菌素(20 mg/kg),继续灌胃2周后,进行口服葡萄糖耐量(OGTT)试验,随后处死大鼠,采集血清和粪便,测定胰岛素和血脂含量,T-RFLP技术分析大鼠肠道菌群结构变化。结果低剂量和高剂量微生态制剂组与模型对照组相比,OGTT试验中1 h和2 h血糖明显降低(P0.01);胰岛素敏感指数显著增加(P0.05);血清FFA、TG、LDL-C含量均降低(P0.05),HDL-C含量升高(P0.01);低剂量组和高剂量组肠道中双歧杆菌含量明显增加(P0.05),肠道其余5种菌含量均无显著差异。结论双歧杆菌微生态制剂能有效改善2型糖尿病造模过程中大鼠的糖脂代谢紊乱,增加肠道双歧杆菌数量。     

抗性淀粉对糖尿病大鼠胰岛素抵抗的影响

目的研究抗性淀粉(RS)对2型糖尿病大鼠胰岛素抵抗的干预作用。方法将40只Wistar大鼠随机选取10只饲以基础饲料(正常对照组),其余30只食用红花油高脂饲料并进行腹腔链脲霉素(20mg/kgbw)注射(模型组)。对诱导成2型糖尿病的大鼠随机分为三组,分别饲食高脂饲料(B组)、高脂RS饲料(C组)、单纯RS饲料(D组);原基础饲料组为A组。继续喂养5w,观察RS对大鼠糖脂代谢、胰岛素敏感指数影响及肝、肾组织病理学变化。结果与糖尿病对照组(B组)相比,RS干预组(C组、D组)糖耐量各时间点血糖值及曲线下面积比明显下降;血胰岛素水平显著降低,而胰岛素敏感指数显著升高;血脂各项指标下降;肝脂肪变性明显减轻,肝糖原合成增加。结论RS可改善糖尿病模型大鼠的糖脂代谢紊乱,提高胰岛素敏感性,具有拮抗或减轻胰岛素抵抗的作用。     

生物素对2型糖尿病大鼠血糖的影响

目的探讨生物素对2型糖尿病大鼠血糖以及糖代谢关键限速酶葡萄糖激酶(GCK)和磷酸烯醇式丙酮酸羧化酶1(PCK1)基因表达的影响。方法 90只健康Wistar大鼠根据血糖随机分为5组(正常对照组,模型组,生物素低、中、高剂量组)。正常对照组给予普通维持饲料,蒸馏水灌胃;模型组给予高脂高糖饲料,蒸馏水灌胃;生物素各剂量组给予高脂高糖饲料同时分别给予生物素0.6、3.0和6.0 mg/kg BW灌胃。在高脂高糖饲料喂养2月后,应用小剂量链脲佐菌素腹腔注射的方法建立2型糖尿病大鼠模型。于造模第10周进行OGTT实验后,处死大鼠。检测血糖、血清胰岛素、肝糖原、肌糖原等指标,用RT-PCR方法检测糖代谢关键限速酶GCK、PCK1基因的表达。结果与模型组相比,生物素各剂量组对空腹血糖、血清胰岛素没有影响,但生物素高剂量组血糖曲线下面积明显下降(P<0.05),餐后30 min血糖值也显著降低(P<0.05)。生物素中剂量组和高剂量组肌糖原含量明显下降(P<0.05)。生物素对糖代谢关键限速酶GCK、PCK1的表达有影响,分别出现了明显的基因表达上调和下调(P<0.05)。结论生物素可能通过影响糖代谢关键酶GCK和PCK1的活性,促进糖酵解和糖原合成而抑制糖异生,从而影响餐后血糖应答。     

长程高脂饮食对实验大鼠糖尿病形成的影响

目的 研究长程高脂饮食及多食少动的现代生活方式对实验大鼠胰岛素抵抗和胰岛功能的影响。方法Wistar大鼠75只喂以普通饲料或高脂饲料共11月，部分高脂大鼠第5月时注射12mg／kg链脲霉素造成糖尿病模型。用腹腔注射糖耐量试验评估胰岛功能，胰岛素耐量试验检测胰岛素敏感性。结果高脂大鼠糖负荷后2h相血糖较普食鼠显著增高，第11月时高脂鼠空腹血糖亦有增高。第4月时，高脂鼠较普食鼠体重显著增加，胰岛素敏感性降低50％；此后二组胰岛素敏感性均有大幅下滑，第9月时需用0．5u／kg的胰岛素才能造成第4月时0．1u／kg胰岛素注射后的血糖降幅，此时高脂鼠的胰岛素敏感性与普食鼠已处于同一水平。结论多食少动的现代生活方式是导致胰岛素抵抗的根本原因，高脂饮食对糖尿病形成的主要作用在于其对胰岛功能的直接损伤。     

脂肪肝和2型糖尿病大鼠抵抗素水平关系的研究

目的探讨抵抗素与胰岛素抵抗、脂肪肝及2型糖尿病的关系。方法雄性SD大鼠51只,随机分为对照组、脂肪肝组、罗格列酮组、二甲双胍组和糖尿病组,分别通过普食、高脂饲养、给药、腹腔注射STZ建立模型,14周时用胰岛素耐量试验衡量大鼠对胰岛素的敏感性,同时检测各组大鼠血浆抵抗素浓度。结果胰岛素耐量试验显示,脂肪肝组用降糖率计算血糖下降幅度仅为对照组的约66%,与脂肪肝组比较,罗格列酮组降糖率明显增高约50%(P<0.01),二甲双胍组降糖率增高约15%(P<0.01)。糖尿病组对胰岛素的敏感性比脂肪肝组高约26%(P<0.01);各组血浆抵抗素之间方差分析未显示统计学差异(P>0.05);各组大鼠血浆抵抗素与降糖率、血糖等无直线相关关系(P>0.05)。结论高脂饲养正常SD大鼠14周产生严重的胰岛素抵抗,罗格列酮、二甲双胍均可显著改善高脂饲养脂肪肝大鼠的胰岛素敏感性;抵抗素可能与大鼠的肥胖、胰岛素抵抗、脂肪肝及2型糖尿病无关,而且不受罗格列酮、二甲双胍干预的影响。     

罗格列酮及饮食干预对胰岛素抵抗大鼠骨骼肌GLUT4转位的影响

目的　探讨罗格列酮对胰岛素抵抗大鼠骨骼肌细胞葡萄糖转运蛋白 4(GLUT4)转位的影响。方法　利用高脂饲料喂养 ,使Sprague -Dawley(SD)大鼠产生胰岛素抵抗 ,用罗格列酮及饮食干预治疗 4周后 ,取骨骼肌组织 ,应用Western -bloting印迹法分析骨骼细胞膜GLUT4表达量。结果　在胰岛素刺激下 ,胰岛素抵抗大鼠骨骼肌细胞膜GLUT4表达较正常大鼠下降 5 2 72 %(P <0 0 0 1) ,罗格列酮及饮食干预组 ,细胞膜GLUT4表达较未干预胰岛素抵抗大鼠分别增加 49 5 3 %、5 0 3 4%(P <0 0 0 1)。结论　罗格列酮可促进胰岛素刺激的GLUT4转位 ,从而改善高脂喂养所引起的骨骼肌组织胰岛素抵抗     

蚕丝水解物对实验性糖尿病大鼠血糖的调节作用

选用若干雄性成年Ｗｉｓｔａｒ大鼠随机分为２组：糖尿病模型组大鼠尾静脉注射小剂量链脲佐菌素（ＳＴＺ,３０ｍｇ／ｋｇＢＷ）３周后,加喂高糖、高脂、高热量饲饲米。选择具有Ⅱ型糖尿病病特征即糖耐量异学、胰岛素高于或等于对照组的３８只大鼠,对照组３６只大鼠不注射ＳＴＺ,仅喂普通饲米,将糖尿病模型组再随机分为２组：糖尿病对照组、糖尿病＋蚕丝水稻物（ＳＨ）组;对照组随机分为正常对照组、正常＋ＳＨ组。每日给予ＳＨ     

Mango modulates body fat and plasma glucose and lipids in mice fed a high-fat diet

Consumption of fruits and vegetables has been investigated for their role in the prevention of many chronic conditions. Among the fruits, mango provides numerous bioactive compounds such as carotenoids, vitamin C and phenolic compounds, which have been shown to have antioxidant and anti-inflammatory properties. The present study examined the effects of dietary supplementation of freeze-dried mango pulp, in comparison with the hypolipidaemic drug, fenofibrate, and the hypoglycaemic drug, rosiglitazone, in reducing adiposity and alterations in glucose metabolism and lipid profile in mice fed a high-fat (HF) diet. Male C57BL/6J mice were randomly divided into six treatment groups (eight to nine/group): control (10?% energy from fat); HF (60?% energy from fat); HF+1 or 10?% freeze-dried mango (w/w); HF+fenofibrate (500?mg/kg diet); HF+rosiglitazone (50?mg/kg diet). After 8 weeks of treatment, mice receiving the HF diet had a higher percentage body fat (P?=?0·0205) and epididymal fat mass (P?=?0·0037) compared with the other treatment groups. Both doses of freeze-dried mango, similar to fenofibrate and rosiglitazone, prevented the increase in epididymal fat mass and the percentage of body fat. Freeze-dried mango supplementation at the 1?% dose improved glucose tolerance as shown by approximately 35?% lower blood glucose area under the curve compared with the HF group. Moreover, freeze-dried mango lowered insulin resistance, as indicated by the homeostasis model assessment of insulin resistance, to a similar extent as rosiglitazone and modulated NEFA. The present findings demonstrate that incorporation of freeze-dried mango in the diet of mice improved glucose tolerance and lipid profile and reduced adiposity associated with a HF diet.     

Alterations in the blood glucose, serum lipids and renal oxidative stress in diabetic rats by supplementation of onion (Allium cepa. Linn)

This study examined the anti-diabetic effect of onion (Allium cepa. Linn) in the streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats were divided into normal rats fed control diet or supplemented with onion powder (7% w/w) and diabetic rats fed control diet or supplemented with onion powder. Diabetes was induced by a single injection of STZ (60 mg/kg, ip) in citrate buffer. The animals were fed each of the experimental diet for 5 weeks. Blood glucose levels of rats supplemented with onion were lower than those of rats fed control diet in the diabetic rats. Onion also decreased the total serum lipid, triglyceride, and atherogenic index and increased HDL-cholesterol/total cholesterol ratio in the diabetic rats. Glutathione peroxidase, glutathione reductase and glutathione S-transferase activities were high in the diabetic rats compared to normal rats and reverted to near-control values by onion. These results indicate that onion decreased blood glucose, serum lipid levels and reduced renal oxidative stress in STZ-induced diabetic rats and this effect might exert the anti-diabetic effect of onion.     

乳清蛋白通过抗氧化作用改善模型大鼠的胰岛素抵抗

目的探讨乳清蛋白对胰岛素抵抗的改善作用。方法用高脂饲料制备胰岛素抵抗模型大鼠,将模型大鼠随机分为0%乳清蛋白(WP)组、5%WP组和15%WP组,每组10只。8周后测定大鼠空腹血糖(FBG)、空腹血浆胰岛素水平(FINS),进行葡萄糖耐量试验(OGTT)并计算葡萄糖曲线下面积(AUC),部分血浆用来测定总抗氧化能力(T-AOC)、超氧化物歧化酶(SOD)、还原型谷胱甘肽(GSH)和丙二醛(MDA)等抗氧化指标。结果摄取乳清蛋白没有改变大鼠FBG和葡萄糖AUC。15%WP组大鼠血浆FINS水平和胰岛素抵抗指数(HOMA-IR)显著低于0%WP组(P<0.05)。15%WP组大鼠血浆T-AOC、SOD和GSH显著高于0%WP组(T-AOC:P<0.01;SOD、GSH:P<0.05),同时血浆MDA含量显著降低(P<0.05)。结论乳清蛋白有效改善了模型大鼠的胰岛素抵抗,这可能和增强机体抗氧化能力有关。     

Up-regulation of PPARγ, heat shock protein-27 and -72 by naringin attenuates insulin resistance, β-cell dysfunction, hepatic steatosis and kidney damage in a rat model of type 2 diabetes

Naringin, a bioflavonoid isolated from grapefruit, is well known to possess lipid-lowering and insulin-like properties. Therefore, we assessed whether naringin treatment ameliorates insulin resistance (IR), β-cell dysfunction, hepatic steatosis and kidney damage in high-fat diet (HFD)-streptozotocin (STZ)-induced type 2 diabetic rats. Wistar albino male rats were fed a HFD (55 % energy from fat and 2 % cholesterol) to develop IR and on the 10th day injected with a low dose of streptozotocin (40 mg/kg, intraperitoneal (ip)) to induce type 2 diabetes. After confirmation of hyperglycaemia (>13·89 mmol/l) on the 14th day, different doses of naringin (25, 50 and 100 mg/kg per d) and rosiglitazone (5 mg/kg per d) were administered orally for the next 28 d while being maintained on the HFD. Naringin significantly decreased IR, hyperinsulinaemia, hyperglycaemia, dyslipidaemia, TNF-α, IL-6, C-reactive protein and concomitantly increased adiponectin and β-cell function in a dose-dependent manner. Increased thiobarbituric acid-reactive substances and decreased antioxidant enzyme activities in the serum and tissues of diabetic rats were also normalised. Moreover, naringin robustly increased PPARγ expression in liver and kidney; phosphorylated tyrosine insulin receptor substrate 1 in liver; and stress proteins heat shock protein (HSP)-27 and HSP-72 in pancreas, liver and kidney. In contrast, NF-κB expression in these tissues along with sterol regulatory element binding protein-1c and liver X receptor- expressions in liver were significantly diminished. In addition, microscopic observations validated that naringin effectively rescues β-cells, hepatocytes and kidney from HFD-STZ-mediated oxidative damage and pathological alterations. Thus, this seminal study provides cogent evidence that naringin ameliorates IR, dyslipidaemia, β-cell dysfunction, hepatic steatosis and kidney damage in type 2 diabetic rats by partly regulating oxidative stress, inflammation and dysregulated adipocytokines production through up-regulation of PPARγ, HSP-27 and HSP-72.     

Quercetin attenuates fasting and postprandial hyperglycemia in animal models of diabetes mellitus

The objective of this study was to investigate the hypoglycemic effects of quercetin (QE) in animal models of diabetes mellitus (DM). A starch solution (1 g/kg) with and without QE (100 mg/kg) or acarbose (40 mg/kg) was orally administered to streptozotocin (STZ)-induced diabetic rats after an overnight fast. Postprandial plasma glucose levels were measured and incremental areas under the response curve were calculated. To study the effects of chronic feeding of QE, five-week-old db/db mice were fed an AIN-93G diet, a diet containing QE at 0.08%, or a diet containing acarbose at 0.03% for 7 weeks after 1 week of adaptation. Plasma glucose and insulin, blood glycated hemoglobin, and maltase activity of the small intestine were measured. Oral administration of QE (100 mg/kg) or acarbose (40 mg/kg) to STZ-treated rats significantly decreased incremental plasma glucose levels 30-180 min after a single oral dose of starch and the area under the postprandial glucose response, compared with the control group. QE (0.08% of diet) or acarbose (0.03% of diet) offered to db/db mice significantly reduced both plasma glucose and blood glycated hemoglobin compared to controls without significant influence on plasma insulin. Small intestine maltase activities were significantly reduced by consumption of QE or acarbose. Thus, QE could be effective in controlling fasting and postprandial blood glucose levels in animal models of DM.     

Sucrose-induced insulin resistance in the rat: modulation by exercise and diet

Isocaloric substitution of sucrose for starch results in hyperinsulinemia and deterioration of glucose tolerance, suggesting a loss of insulin sensitivity. In this study we have quantitated the insulin resistance which develops with sucrose feeding, and evaluated the ability of dietary fiber, or an increase in skeletal muscle activity, to inhibit, or even prevent, the detrimental effect of sucrose feeding on in vivo insulin action. Thus, 6-wk-old rats were fed one of the following regimens for three weeks: a 64% cornstarch diet (C), a 32% cornstarch + 32% sucrose diet (S), the (S) diet containing added wheat bran fiber (S/F), and the (S) diet given to rats running spontaneously in exercise wheel cages (S/ET). Insulin sensitivity was evaluated by comparing steady-state plasma glucose (SSPG) concentrations at constant plasma insulin levels approximately 70 microU/ml attained during the continuous infusion of epinephrine (0.08 micrograms/kg/min), propranolol (1.7 micrograms/kg/min), glucose (8 mg/kg/min), and insulin (2.5 mU/kg/min) to each experimental group. The results show that rats fed the S diet had a significant increase (p less than 0.01) in mean (+/- SEM) SSPG concentration compared with rats fed the C diet (255 +/- 14 versus 165 +/- 3 mg/dl). SSPG concentrations, although lower (p less than 0.05) in rats fed S/F (205 +/- 8 mg/dl), were still higher (p less than 0.05) than the C levels (165 +/- 3 mg/dl). However, S/ET completely inhibited the increase in SSPG concentration seen in rats fed S and the values were actually lower (p less than 0.05) than in rats fed C (100 +/- 10 versus 165 +/- 3 mg/dl). In conclusion 1) sucrose feeding results in a loss of insulin sensitivity in normal rats; 2) addition of fiber attenuates, but does not completely prevent, the loss of insulin sensitivity associated with feeding sucrose; 3) exercise training prevents the loss of insulin sensitivity seen in sucrose-fed rats, and actually improves glucose uptake beyond that seen in the control group. These results document the profound effect of environmental factors on in vivo insulin action.