不同性别大鼠在2型糖尿病造模过程中的稳定性

目的研究不同性别大鼠在2型糖尿病造模过程中的成功率及模型的稳定性。方法高糖高脂饮食联合腹腔注射小剂量链脲佐菌素诱导建立雄、雌性大鼠2型糖尿病模型。成模后所有大鼠每周固定时间测血糖和体重。观察24周后,心脏穿刺取血,测定空腹血糖（FPG）、血清胰岛素（FINS）、HbA1c、甘油三脂（TG）、胆固醇（TC）、高密度脂蛋白-胆固醇（HDL-C）、低密度脂蛋白-胆固醇（LDL-C）。结果单纯高糖高脂饮食喂养,雄、雌性大鼠血糖与正常组无显著差异;STZ注射后,雄性大鼠血糖升高并逐渐平稳,而雌性需两次STZ注射,模型才比较稳定。实验结束时,雄、雌性糖尿病大鼠FPG、FINS、HOMA-IR以及TG、TC、LDL-C均显著升高,说明模型存在胰岛素抵抗和脂代谢紊乱。结论高糖高脂饲料加一次性小剂量链脲佐菌素腹腔注射,可成功建立雄性大鼠2型糖尿病模型,而同等剂量,雌性模型需两次STZ。雄、雌性糖尿病大鼠模型具有高血糖、脂质代谢紊乱和胰岛素抵抗特点。造模成功率及稳定性与性别有关,雄性大鼠较雌性大鼠成模率高,稳定性好,且耗时更短。     

不同剂量链尿佐菌素诱导2型糖尿病大鼠模型的研究

目的:探讨不同剂量链脲佐菌素(Streptozotocin,STZ)联合高糖高脂饮食对2型糖尿病大鼠模型建立的影响。方法:90只8周龄SD雄性大鼠随机平均分为六组:普通饲料喂养+缓冲液组、高糖高脂饲料喂养+缓冲液(H.E组)、高糖高脂饲料喂养+35mg/kg链尿佐菌素组(H.E+35 mg/kg STZ组)、高糖高脂饲料喂养+45 mg/kg链尿佐菌素组(H.E+45 mg/kg STZ组)、高糖高脂饲料喂养+55 mg/kg链尿佐菌素组(H.E+55 mg/kg STZ组)及高糖高脂饲料喂养+65 mg/kg链尿佐菌素组(H.E+65 mg/kg STZ组),高糖高脂饲料喂养4周后诱导胰岛素抵抗,继之腹腔注射STZ,建立2型糖尿病大鼠模型。检测体重、胰岛素、空腹血糖、血脂、胰岛素敏感指数(ISI)。结果:与常规饮食组相比,高糖高脂饮食各组大鼠出现空腹血浆胰岛素(FINS)、空腹血糖(FBG)、血清甘油三脂(TG)、总胆固醇(TC)、游离脂肪酸(FFA)显著升高(P0.01),ISI显著下降(P0.01)。不同剂量STZ注射,H.E+45 mg/kg STZ组成模率最高且无自愈现象。结论:通过STZ腹腔注射联合高糖高脂饮食可成功复制出实验性2型糖尿病动物模型,45 mg/kg为STZ理想注射剂量。     

链尿佐菌素加高糖高脂饮食复制大鼠2型糖尿病模型

目的链尿佐菌素加高糖高脂饮食诱导大鼠2型糖尿病模型的建立。方法SD雄性大鼠高糖高脂饲料喂养3周后,采血检测空腹血糖及血清胰岛素,按25mg/g体重剂量一次性腹腔内注射链尿佐菌素,3d后,行糖耐量实验,对糖耐量异常大鼠继续喂以高糖高脂饲料,在第2、第4周再两次采血检测糖尿病鼠空腹血糖及血清胰岛素。结果与对照组比较,高糖高脂喂养大鼠血清胰岛素明显上升（P〈0.01）,但血糖无变化（P〉0.05）,糖尿病鼠血糖及血清胰岛素均显著的高于对照组（P〈0.01）。结论高糖高脂喂养能致大鼠明显的高胰岛素血症,辅以小剂量一次性注射链尿佐菌素而造成的糖耐量异常,可成功复制出2型糖尿病大鼠模型。     

糖尿病动物模型的特点及影响因素分析

糖尿病是以血糖浓度增高、胰岛素缺乏或作用下降为主要特征的慢性疾病,并能引起脂肪和蛋白质代谢紊乱。为了探索糖尿病的发病机理、血糖的调节机制以及评价等问题,建立能够模拟人类疾病特征的实验动物模型也备受关注。由于II型糖尿病或胰岛素抵抗与糖脂代谢密切相关,肥胖和高能量膳食摄入可增加其发病风险,所以高脂高糖膳食诱导肥胖型的糖尿病动物模型以及在此基础上联合小剂量链脲佐菌素（streptozocin,SZT）的造模方法被广泛应用。本文主要综述了II型糖尿病的机理,并就食物调节在糖尿痛发病过程中的作用和影响,浅谈Ⅱ型糖尿痛的特点和制备过程中的的注意事项,以供参考。     

胰岛素对2型糖尿病骨质疏松大鼠血清与骨OPG、RANKL表达的影响

目的:探讨胰岛素对2型糖尿病骨质疏松大鼠血清及骨OPG(osteoprotegerin)、RANKL(OPG receptor activator nuclear factork B)表达水平的影响。方法:以高脂高糖饲料喂养4周同时饮用3%果糖水导致胰岛素抵抗小鼠,再以小剂量链脲佐菌素(30mg/kg)腹腔注射1次,2周后诱导建立2型糖尿病小鼠模型。对照组动物则给予正常饲料及饮用水进行喂养。模型建立成功后,对模型2组大鼠进行胰岛素治疗,分别采用OPG和RANKLelisa试剂盒对正常动物模型和糖尿病动物模型血清和骨组织中OPG,RANKL含量进行比较分析,采用血糖分析仪对不同组动物的血糖进行比较分析,采用骨密度分析仪对动物的骨密度进行分析,了解高血糖对于骨密度及血清,骨组织中OPG,RANKL含量的影响以及胰岛素对高血糖骨质疏松造成的结果的影响。结果:相较于正常组大鼠,模型组大鼠血清及髂骨中OPG、血糖、糖化血红蛋白、髂骨密度表达显著下调(P0.05),而RANKL表达显著上调(P0.05),胰岛素处理的模型大鼠血清及骨中OPG含量较模型组大鼠显著升高,血清及骨组织中RANKL表达显著下调(P0.05)。结论:胰岛素能够显著降低2型糖尿病骨质疏松大鼠血清及骨组织中RANKL的表达,显著上调OPG的表达。     

高脂饲喂联合链脲佐菌素诱导的Beagle犬糖尿病模型

目的应用高脂饲喂联合链脲佐菌素(STZ)构建Beagle犬T2DM模型,并观察其相关特征。方法将普通级雄性Beagle犬30只随机分为3组:对照组,高脂组,糖尿病模型组,每组10只。糖尿病模型组饲喂高脂饲料同时在饲喂2个月时注射STZ;高脂组饲喂高脂饲料;对照组饲喂普通饲料,连续饲喂5个月。定期测定动物Lee指数、空腹血糖、胰岛素、尿糖,并在3月时进行OGTT试验,试验结束后进行血脂等血液生化检测和肝、胰腺组织病理检查。结果高脂组和糖尿病模型组高脂饲养2个月后Lee指数显著增加(P0.01),并出现高胰岛素血症和胰岛素抵抗伴血脂异常;糖尿病模型组STZ注射后空腹血糖显著升高(P0.01),且持续3个月维持在高血糖水平;而高脂组的空腹血糖无明显变化(P0.05),糖尿病模型组OGTT试验3 h血糖值11.1mmol/L,且3 h未恢复,胰腺组织病理学检查出现一定程度的损伤和病变。结论高脂饲料饲喂诱导Beagle犬胰岛素抵抗和高血脂症,但未能形成高血糖状态,而高脂饲料饲喂联合注射STZ后Beagle犬在出现高血脂症的同时发生胰岛素抵抗,与人类T2DM的胰岛素抵抗伴高血糖、高胰岛素血症和高血脂等典型症状相似。     

2型糖尿病大鼠的尿液代谢组学改变

目的 通过检测2型糖尿病大鼠尿液代谢谱的变化.探讨代谢组学在糖尿病研究中的应用.方法 SD大鼠高糖高脂饲料喂养6周后,腹腔注射链脲菌素(Streptozotocin,STZ)37 mg/kg建立2型糖尿病模型,动态检测空腹血糖(FBG)变化,检测甘油三酯(TC)、总胆固醇(TC)、游离脂肪酸(FFA)及胰岛素(INS)...     

黄连素对糖尿病大鼠胰岛素抵抗的治疗作用*

目的:探讨黄连素对链脲佐菌素所致糖尿病大鼠胰岛素抵抗的治疗作用。方法:采用链脲佐菌素腹腔注射的方式建立大鼠糖尿病模型,将实验大鼠分为5组:分别为模型组、黄连素低(100 mg/kg)、黄连素中(200 mg/kg)、黄连素高(300 mg/kg)剂量组和阳性对照组(二甲双胍:50 mg/kg),每组10只。另取10只正常大鼠作为正常组。黄连素低、中、高剂量组小鼠每天分别灌胃100、200和300 mg/kg黄连素;对照组每天灌胃二甲双胍50 mg/kg;正常组和模型组每天给予相同体积的生理盐水进行灌胃;1次/天,连续灌胃4周。通过测定大鼠血FBG、果糖胺水平,OGTT实验,胰岛素(FINS)水平,并计算大鼠胰岛素抵抗指数(HOMA-IR)来评价黄连素对糖尿病大鼠胰岛素抵抗作用。结果:与正常组相比,给药前模型组大鼠静脉血FBG含量显著升高(P＜0.05);与模型组比较,给药2周及以后给药4周后阳性对照组、黄连素中剂量组和高剂量组大鼠静脉血FBG含量均显著下降(P＜0.05);给药4周后,阳性对照组、黄连素低、中、高剂量组OGTT实验结果显示在不同时间节点的血糖值均显著低于模型组(P＜ 0.05),阳性对照组、黄连素低、中、高剂量组FBG、果糖胺水平和HOMA-IR指标均低于模型组(P＜0.05);而胰岛素水平水平较模型组显著升高(P＜0.05)。结论:黄连素可明显降低大鼠的空腹血糖、果糖胺含量,提高胰岛素含量,对链脲佐菌素所致糖尿病大鼠的胰岛素抵抗有明显治疗作用。且一定范围内,黄连素剂量越高,对糖尿病大鼠胰岛素抵抗作用越明显。     

STZ诱导恒河猴糖尿病动物模型的建立

目的复制稳定的链脲佐菌素诱导糖尿病恒河猴动物模型。方法健康恒河猴5只,小剂量（30mg/kg）多次静脉注射链脲佐菌素,分别在注射后2、3个月进行葡萄糖耐量实验并连续观察血糖、胰岛素、C肽的变化。连续观察12个月。结果随着时间推移,动物出现典型的糖尿病症状。3只动物的血糖静脉注射1次后持续10周稳定,另外2只分别进行了第2、3次注射。动物血糖在12个月内平稳上升、胰岛素、C肽分泌持续下降。2个月时葡萄糖耐量减低明显（P〈0.01）。结论小剂量多次注射STZ后恒河猴可出现持续、稳定的糖尿病表现,可作为相关研究的动物模型。     

明日叶查尔酮对2型糖尿病大鼠红细胞胰岛素受体亲和力的影响

目的:研究明日叶查尔酮对2型糖尿病大鼠红细胞胰岛素受体亲和力的影响.方法:将高脂喂养加链脲佐菌素注射诱发的2型糖尿病大鼠随机分为4组,每组10只.糖尿病对照组和高、中、低剂量组喂饲高脂饲料分别经口灌胃明日叶查尔酮0、30、10、5mg (kg·bw)-1,正常对照组为正常大鼠喂饲普通饲料,连续4周.测定空腹血糖、血清胰岛素与MDA、红细胞胰岛素受体结合常数与结合容量等指标.结果:高剂量组的高亲和力与低亲和力胰岛素受体结合常数高于糖尿病对照组,血糖、胰岛素和MDA含量则降低,差异均有显著性(P＜0.05).结论:明日叶查尔酮能提高2型糖尿病大鼠红细胞胰岛素受体亲和力,改善胰岛素抵抗.     

Effects of streptozotocin and dietary fructose on delta-6 desaturation in spontaneously hypertensive rat liver

We have investigated the effects of hypertension associated with diabetes mellitus on polyunsaturated fatty acid biosynthesis. For this purpose, two rat models for these pathologies have been established: a type 1 diabetic hypertensive model obtained by streptozotocin injection to spontaneously hypertensive rat (SHR), followed or not by insulin treatment (experiment 1); a type 2 diabetic hypertensive model by feeding SHR with a fructose enriched diet (experiment 2). Liver gene expression of delta-6 desaturase (D6D), microsomal D6D activities and fatty acid composition of total lipids were estimated. In experiment 1, an increase of linoleic acid (18:2 n-6) level was observed in the streptozotocin group. D6D gene expression appeared depressed in both experimental groups. Insulin did not reverse the streptozotocin effect in SHR, as it does in insulin-dependent diabetic rats. In experiment 2, the results showed a decrease of 18:2 n-6 and of long chain products of desaturation in rats fed on fructose diet. Delta-6 n-3 desaturase activity was significantly increased, whereas gene expression tended to decrease. Feeding fructose induced a significant increase in delta-9 desaturated products, suggesting a stimulation of stearoyl-CoA desaturase. These changes in monounsaturated fatty acids strongly differ from those observed in the streptozotocin experiment, indicating that the effects on lipogenesis of hypertension linked to diabetes differ according to the type of diabetes. Then, these results indicate that the liver steatosis observed during genetic hypertension was reinforced by fructose feeding. All together, the present results showed that hypertension associated to type 1 or type 2 diabetes exacerbated the damage caused by diabetes or hypertension alone on liver lipid metabolism. The metabolic effects induced by fructose being very similar to those found in human NIDDM, SHR fed a fructose-rich diet appears to be an appropriate model for studying the consequences of the combination of hypertension and NIDDM in the metabolic syndrome diseases.     

Obesity, insulin resistance and diabetes in the sand rat exposed to a hypercaloric diet; possible protective effect for IL1-β

It is well established that, upon changing their natural desert low caloric (succulent halophilic plants) to a regular laboratory high caloric diet, sand rats undergo various phenotypic changes depending on their genetic background and including obesity and various degrees of insulin resistance. Our aim was to investigate the acute effects of Interleukin-1β (IL-1β) and Interferon-γ (IFN-γ) on glucose-induced insulin secretion in normal lean sand rats maintained on their natural diet and in obese insulin resistant normoglycemic or type 2 diabetic animals after a 9-month high caloric diet. Animals were fed either a low or a high caloric diet; after 9 months, pancreatic islets were isolated and incubated in the presence of increasing cytokine concentrations. At the end of the high-energy diet, animals were all over-weight, and probably due to a different genetic background, they displayed either insulin resistance, hyperinsulinemia and normoglycemia or a marked type-2 diabetic state. Pancreatic islets from obese insulin resistant normoglycemic animals were much more sensitive and responsive to IL-1β when compared to lean controls. The cytokine was inefficient in diabetic islets. In conclusion, the markedly increased insulinotropic effect of IL-1β in obese diabetes-resistant sand rat could participate and be involved in pancreatic β-cell hyperactivity that compensates for insulin resistance and thereby prevent the development of type 2 diabetes in these animals.     

High fructose intake significantly reduces kidney copper concentrations in diabetic, islet transplanted rats

Trace element status is known to be altered in the diabetic state, although the factors affecting trace element homeostasis in this condition are not well understood. The authors examined the effects of a high fructose diet (40% wt:wt) vs a control diet on the copper (Cu), zinc (Zn), and iron (Fe) concentrations in the kidney, plasma, and red blood cells of islet transplanted (TX) and shamoperated (SHAM) rats. Male, Wistar Furth rats made diabetic by streptozotocin injection (55 mg/kg, iv) were given an intraportal islet transplant (1000 islets); control animals were shaminjected, shamoperated (SHAM). Rats within TX and SHAM groups were assigned to either a high fructose diet (40% fructose, 25% cornstarch, FR) or a purified control diet (33% cornstarch, 33% dextrose, CNTL) containing identical amounts of mineral mixture for a period of 6 wk. Kidney Cu concentration was significantly elevated among hyperglycemie TXCNTL rats (224 ± 25 nmol/g wet wt), but was markedly reduced in hyperglycemic TXFR rats (109 ± 14 nmol/g) relative to normoglycemic controls. This occurred in spite of similar levels of glucose, insulin (fed and fasted), insulin secretory capacity, body weight, and food intake in the TXCNTL and TXFR groups. Among the subgroup of rats with normal glucose levels post-TX, kidney Cu levels normalized and were unaffected by dietary treatment (normoglycemic TXCNTL = 60 ± 5 nmol/g; normoglycemic TXFR = 40 ± 2 nmol/g). Kidney Cu concentrations also were unaffected by fructose feeding in SHAM animals (CNTL, 60 ± 4 nmol/g and FR, 51 ± 5 nmol/g). Kidney Zn and Fe concentrations were similar among the treatment groups. Plasma and red blood cell (RBC) Cu, Zn, and Fe concentrations were also similar among the groups. Since fructose feeding led to a substantial reduction of kidney Cu concentrations in the presence of hyperglycemia, the authors suggest that this model can be useful in examining effects of altered kidney Cu accumulation in the diabetic animal.     

Ginsenoside Rh2 is one of the active principles of Panax ginseng root to improve insulin sensitivity in fructose-rich chow-fed rats.

Ginsenoside Rh2, one of the ginsenosides contained in the Panax ginseng root, was employed to screen the effect on insulin resistance of rats induced by a diet containing 60% fructose. Single intravenous injection of ginsenoside Rh2 decreased the plasma glucose concentrations in 60 minutes in a dose-dependent manner from 0.1 mg/kg to 1 mg/kg in rats with insulin resistance induced by fructose-rich chow. Repeated intravenous injection of ginsenoside Rh2 (1 mg/kg per injection, 3 times daily) into rats which received fructose-rich chow for 3 consecutive days decreased the value of glucose-insulin index, the product of the areas under the curve of glucose and insulin during the intraperitoneal (i.p.) glucose tolerance test. This means that ginsenoside Rh2 has an ability to improve insulin action on glucose disposal. The plasma glucose lowering action of tolbutamide, induced by the secretion of endogenous insulin, is widely used to characterize the formation of insulin resistance. Time for the loss of plasma glucose lowering response to tolbutamide (10 mg/kg, i.p.) in rats during insulin resistance induction by fructose-rich chow was also markedly delayed by the repeated treatment of ginsenoside Rh2, as compared to the vehicle-treated control. Thus, the repeated treatment of ginsenoside Rh2 delayed the development of insulin resistance in high fructose feeding rats. Increase of insulin sensitivity by ginsenoside Rh2 was further identified using the plasma glucose lowering action of exogenous insulin in streptozotocin-induced diabetic rats (STZ-diabetic rats). Repeated injection of ginsenoside Rh2 at the same dosing (1 mg/kg, 3 times daily) into STZ-diabetic rats for 10 days made an increase of the responses to exogenous insulin. Taken together, it can be concluded that ginsenoside Rh2 has an ability to improve insulin sensitivity and it seems suitable to use ginsenoside Rh2 as an adjuvant for diabetic patients and/or the subjects wishing to increase insulin sensitivity.     

Formononetin Ameliorates Diabetic Neuropathy by Increasing Expression of SIRT1 and NGF

Diabetic neuropathy is commonly observed complication in more than 50 % of type 2 diabetic patients. Histone deacetylases including SIRT1 have significant role to protect neuron from hyperglycemia induced damage. Formononetin (FMNT) is known for its effect to control hyperglycemia and also activate SIRT1. In present study, we evaluated effect of FMNT as SIRT1 activator in type 2 diabetic neuropathy. Type 2 diabetic neuropathy was induced in rats by modification of diet for 15 days using high fat diet and administration of streptozotocin (35 mg/kg/day, i. p.). FMNT treatment was initiated after confirmation of type 2 diabetes. Treatment was given for 16 weeks at 10, 20 and 40 mg/kg/day dose orally. FMNT treatment‐controlled hypoglycemia and reduced insulin resistance significantly in diabetic animals. FMNT treatment reduced oxidative stress in sciatic nerve tissue. FMNT treatment also reduced thermal hyperalgesia and mechanical allodynia significantly. It improved conduction velocity in nerve and unregulated SIRT1 and NGF expression in sciatic nerve tissue. Results of present study indicate that continuous administration of FMNT protected diabetic animals from hyperglycemia induced neuronal damage by controlling hyperglycemia and increasing SIRT1 and NGF expression in nerve tissue. Thus, FMNT can be an effective candidate for treatment of type 2 diabetic neuropathy.     

Anti-diabetic effects of electrolyzed reduced water in streptozotocin-induced and genetic diabetic mice

Oxidative stress is produced under diabetic conditions and is likely involved in progression of pancreatic beta-cell dysfunction found in diabetes. Both an increase in reactive oxygen free radical species (ROS) and a decrease in the antioxidant defense mechanism lead to the increase in oxidative stress in diabetes. Electrolyzed reduced water (ERW) with ROS scavenging ability may have a potential effect on diabetic animals, a model for high oxidative stress. Therefore, the present study examined the possible anti-diabetic effect of ERW in two different diabetic animal models. The genetically diabetic mouse strain C57BL/6J-db/db (db/db) and streptozotocin (STZ)-induced diabetic mouse were used as insulin deficient type 1 and insulin resistant type 2 animal model, respectively. ERW, provided as a drinking water, significantly reduced the blood glucose concentration and improved glucose tolerance in both animal models. However, ERW fail to affect blood insulin levels in STZ-diabetic mice whereas blood insulin level was markedly increased in genetically diabetic db/db mice. This improved blood glucose control could result from enhanced insulin sensitivity, as well as increased insulin release. The present data suggest that ERW may function as an orally effective anti-diabetic agent and merit further studies on its precise mechanism.     

Effects of selenium on endothelial dysfunction and metabolic profile in low dose streptozotocin induced diabetic rats fed a high fat diet

Endothelial dysfunction develops as a result of oxidative stress and is responsible for diabetic vascular complications. We investigated the effects of selenium on endothelial dysfunction and oxidative stress in type 2 diabetic rats. Male Wistar rats were divided into five groups: controls, untreated diabetics, and diabetics treated with 180, 300, 500 mcg/kg selenium each day. Diabetes was induced by a single intraperitoneal injection of low dose streptozotocin to rats fed a high fat diet. Endothelium-dependent and -independent relaxations were measured in the thoracic aorta. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and endothelial nitric oxide synthase (eNOS) mRNA expressions were analyzed using real-time polymerase chain reaction (RT-PCR). Fasting blood glucose, lipid profile, lipid oxidation, insulin and nitric oxide were measured in blood samples. Malondialdehyde, superoxide dismutase, catalase and glutathione peroxidase levels were measured in liver samples. RT-PCR showed that selenium reversed increased NADPH oxidase expression and decreased eNOS expression to control levels. Selenium also improved the impairment of endothelium-dependent vasorelaxation in the diabetic aorta. Selenium treatment significantly decreased blood glucose, cholesterol and triglyceride levels, and enhanced the antioxidant status in diabetic rats. Our findings suggest that selenium restores a normal metabolic profile and ameliorates vascular responses and endothelial dysfunction in diabetes by regulating antioxidant enzyme and nitric oxide release.     

Central leptin increases insulin sensitivity in streptozotocin-induced diabetic rats

This study examined the effect of intracerebroventricular leptin on insulin sensitivity in streptozotocin (STZ)-induced diabetic rats. Male Wistar rats were cannulated in the lateral ventricle and, after recovery, administered either intravenous STZ (50 mg/kg) to induce diabetes or citrate buffer. Chronic leptin (10 microg/10 microl icv) or vehicle injections were administered daily for 14 days beginning 2 days after establishment of hyperglycemia in the diabetic animals. At the end of the 2 wk of injections, insulin sensitivity was measured by the steady-state plasma glucose (SSPG) method. Blood glucose concentrations were dramatically reduced and normalized by the 4th day in diabetic animals receiving intracerebroventricular leptin treatment. Diabetic animals exhibited insulin resistance, whereas intracerebroventricular leptin significantly enhanced insulin sensitivity, as indicated by decreased SSPG. Circulating leptin levels were not increased in animals injected with intracerebroventricular leptin. Thus the increased peripheral insulin sensitivity appears to be due solely to the presence of leptin in the brain, not to leptin acting peripherally. These data imply that inadequate central leptin signaling may lead to insulin resistance.