A new rat model of type 2 diabetes: the fat-fed, streptozotocin-treated rat

This study was initiated to develop an animal model of type 2 diabetes in a non-obese, outbred rat strain that replicates the natural history and metabolic characteristics of the human syndrome and is suitable for pharmaceutical research. Male Sprague-Dawley rats (n = 31), 7 weeks old, were fed normal chow (12% of calories as fat), or high-fat diet (40% of calories as fat) for 2 weeks and then injected with streptozotocin (STZ, 50 mg/kg intravenously). Before STZ injection, fat-fed rats had similar glucose concentrations to chow-fed rats, but significantly higher insulin, free fatty acid (FFA), and triglyceride (TG) concentrations (P < .01 to .0001). Plasma insulin concentrations in response to oral glucose (2 g/kg) were increased 2-fold by fat feeding (P < .01), and adipocyte glucose clearance under maximal insulin stimulation was significantly reduced (P < .001), suggesting that fat feeding induced insulin resistance. STZ injection increased glucose (P < .05), insulin (P < .05), FFA (P < .05), and TG (P < .0001) concentrations in fat-fed rats (Fat-fed/STZ rats) compared with chow-fed, STZ-injected rats (Chow-fed/STZ rats). Fat-fed/STZ rats were not insulin deficient compared with normal chow-fed rats, but had hyperglycemia and a somewhat higher insulin response to an oral glucose challenge (both P < .05). In addition, insulin-stimulated adipocyte glucose clearance was reduced in Fat-fed/STZ rats compared with both chow-fed and Chow-fed/STZ rats (P < .001). Finally, Fat-fed/STZ rats were sensitive to the glucose lowering effects of metformin and troglitazone. In conclusion, Fat-fed/STZ rats provide a novel animal model for type 2 diabetes, simulates the human syndrome, and is suitable for the testing of antidiabetic compounds.     

吡咯烷二硫代氨基甲酸酯对2型糖尿病大鼠大血管损伤的保护作用

目的 观察吡咯烷二硫代氨基甲酸酯(PDTC)的降糖作用,以及对2型糖尿病(T2DM)大鼠主动脉血管内皮诱生型一氧化氮合酶(iNOS)表达及硝基酪氨酸(NT)生成的影响.方法 雄性WistarA大鼠,随机分为两组,正常对照组(NC组)和高脂饮食组(HFD组),喂养8 w后,HED组腹腔注射小剂量链脲佐菌素(STZ),诱导成功的T2DM大鼠随机分为糖尿病组(DM组)和PDTC治疗组(PDTC组),PDTC治疗组接受PDTC(50 mg/kg)治疗,持续1周,断头处死后留取血浆检测血糖及各种生化指标;留取主动脉组织,检测主动脉组织匀浆中丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)的含量;HE染色观察主动脉组织形态学变化,免疫组化观察各组大鼠主动脉内皮iNOS、NT的表达.结果 PDTC治疗1w后,PDTC组大鼠空腹血糖、MDA水平明显低于DM组;SOD和GSH-Px水平明显高于DM组(P<0.01).免疫组化结果显示:iNOS、NT在DM组大鼠主动脉内皮表达水平明显高于NC组;在PDTC治疗组大鼠主动脉内皮表达水平明显低于DM组.结论 PDTC不仅具有降血糖作用,而且可以减少iNOS的表达,进而减少过氧亚硝基阴离子(ONOO<'->)及NT的产生,延缓了糖尿病大血管并发症的发生.早期应用PDTC可预防T2DM因"代谢记忆"所致的大血管损伤.     

蜕皮甾酮对2型糖尿病大鼠肾组织氧化应激的影响

目的探讨蜕皮甾酮对2型糖尿病(T2DM)大鼠肾组织氧化应激的影响。方法选择70只雄性SD大鼠,高脂喂养8周后,对60只用链脲佐菌素腹腔注射建立T2DM模型,然后分T2DM组、蜕皮甾酮治疗组(A组)、阿托伐他汀治疗组(B组)、吡格列酮治疗组(C组);另10只为正常对照组(对照组)。干预治疗6周后杀检,检测各组空腹血糖(FPG)、尿素氮(BUN)、血肌酐(SCr)、血脂及尿肌酐清除率(Ccr),用ELISA法检测肾组织超氧化物岐化酶(SOD)、丙二醛(MDA)、一氧化氮合酶(NOS)。结果与对照组比较,各组FPG、BUN、血脂、Ccr、SOD、MDA、NOS升高,SCr降低,均以T2DM组明显(P<0.05或<0.01);与B、C组比较,A组Ccr、LDL-C、NOS、MDA降低,SOD升高(P<0.05或<0.01)。结论皮甾酮能降低T2DM大鼠的Ccr,其可能通过减少肾组织MDA、NOS,升高SOD发挥抗氧化效应,因而具有防治DKD的作用。     

Association between the characteristics of metabolic syndrome and Alzheimer’s disease

Various epidemiological studies have shown that type 2 diabetes and metabolic syndrome are highly correlated with Alzheimer’s disease (AD). Here, we sought to assess the impact of metabolic syndrome characteristics on the progression of AD. Five-week-old male, spontaneously hypertensive (n?=?32) and Wistar Kyoto (abbreviated WKY; n?=?8) rats were divided into 5 groups (each n?=?8): WKY, hypertension (HTN), streptozotocin-induced diabetes (STZ), high-fat diet (HFD), and STZ + high-fat diet-induced diabetes mellitus (DM). All animals were sacrificed and samples of the blood, liver, and brain were collected for further biological analysis. During the 15-week period of induction, the STZ and DM groups (animals injected with low-dose STZ) had significantly higher fasting glucose levels; the HFD group had elevated insulin levels, but normal blood glucose levels. The HFD and DM groups had hypercholesterolemia and higher hepatic levels of triglycerides and cholesterol. Additionally, correlations between HFD and elevated brain amyloid-beta 42 (Aβ-42), hyperglycemia and down-regulation of brain insulin receptor, and serum Aβ-42 and hepatic triglyceride concentrations (r²?=?0.41, p?<?0.05) were observed. Serum C-reactive protein and malondialdehyde did not appear to have a significant influence on the association with biomarkers of AD. Thus, our study demonstrated that rats with characteristics of metabolic syndrome had a large number of biomarkers predicting AD; however, no relationship between traditional inflammatory and oxidative markers and AD was found. Further studies are necessary to prove that these findings in rats are relevant to AD processes in humans.     

Hesperidin and naringin attenuate hyperglycemia-mediated oxidative stress and proinflammatory cytokine production in high fat fed/streptozotocin-induced type 2 diabetic rats

Abnormal regulation of glucose and impaired carbohydrate utilization that result from a defective or deficient insulin are the key pathogenic events in type 2 diabetes mellitus (T2DM). The present study was hypothesized to investigate the beneficial effects of hesperidin and naringin on hyperglycemia-induced oxidative damage in HFD/STZ-induced diabetic rats. Diabetes was induced by feeding rats with an HFD for 2 weeks followed by an intraperitoneal injection of STZ (35 mg/kg body weight). An oral dose of 50 mg/kg hesperidin or naringin was daily given for 4 weeks after diabetes induction. At the end of the experimental period, blood was obtained from jugular vein and livers were rapidly excised and homogenized for biochemical assays. In the diabetic control group, levels of glucose, glycosylated hemoglobin (HbA1c%), MDA, NO, TNF-α and IL-6 were significantly increased, while serum insulin, GSH, vitamin C, and vitamin E levels were decreased. Both hesperidin and naringin administration significantly reversed these alterations. Moreover, supplementation with either compound significantly ameliorated serum and liver MDA, NO and glutathione, and liver antioxidant enzymes. Although detailed studies are required for the evaluation of the exact mechanism of the ameliorative effects of hesperidin and naringin against diabetic complications, these preliminary experimental findings demonstrate that both hesperidin and naringin exhibit antidiabetic effects in a rat model of T2DM by potentiating the antioxidant defense system and suppressing proinflammatory cytokine production.     

Eugenosedin-A improves glucose metabolism and inhibits MAPKs expression in streptozotocin/nicotinamide-induced diabetic rats

This study examined the effects of eugenosedin-A (Eu-A) in a streptozotocin (STZ)/nicotinamide-induced rat model of type II diabetes mellitus (T2DM). Six-week-old Sprague–Dawley rats were randomly divided into three groups: (1) RD group, normal rats fed a regular diet (RD), (2) DM group, T2DM rats fed a high-fat diet, and (3) Eu-A group, T2DM rats fed a high fat diet plus oral Eu-A (5 mg/kg/day). After 30 days, the DM group had higher body weight, higher blood glucose and lower insulin levels than the RD group. The DM group also had increased protein expression of glycogen synthase kinase (GSK) in liver and skeletal muscle and decreased protein expression of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), IRS-2, AMP-activated protein kinase (AMPK), glucose transporter-4 (GLUT-4), glucokinase (GCK), and peroxisome proliferator-activated receptor γ (PPAR-γ). STZ/nicotinamide-induced T2DM increased the expression of mitogen-activated protein kinases (MAPKs: p38, ERK, JNK) and inflammatory p65 protein. In the Eu-A treated T2DM rats, however, blood glucose was attenuated and the insulin concentration stimulated. Changes in IR, IRS-1 and IRS-2 proteins as well as AMPK, GLUT-4, GCK, GSK, PPAR-γ, MAPKs, and inflammatory p65 proteins were ameliorated. These results suggested that Eu-A alleviates STZ/nicotinamide-induced hyperglycemia by improving insulin levels and glucose metabolism, and inhibiting the MAPKs- and p65-mediated inflammatory pathway.     

The effect of a single bout of exhaustive exercise on muscle carbohydrate and lipid metabolism in a rat model of type 2 diabetes mellitus

The aim of the present study was to estimate whether a single bout of exhaustive exercise influences the glycogen and triglyceride (TG) content in red and white gastrocnemius muscle and in the liver of rats with experimental type 2 diabetes. Experiments were carried out on male Wistar rats fed from 8 to 11 weeks of age with isocaloric standard or high-fat diet (HFD) with a previous injection of low-dose of streptozotocin (STZ) or vehicle at 2 days of age (I, control group: II, HFD; III, STZ; IV, STZ+HFD). Group IV (STZ+HFD) represents a model of type 2 diabetes. Basal liver glycogen was markedly lower in all the studied groups compared to controls. Glycogen concentration after exercise fell significantly in the examined tissues in all groups in comparison to basal conditions. A significant TG accumulation in examined tissues was observed in all the studied groups in comparison to controls. Exercise decreased tissue TG content in all the groups, but it remained significantly higher in the experimental groups vs. control. We conclude that in this model of type 2 diabetes, a single bout of exercise reveals defective utilization of tissue carbohydrates and lipids. Received: 5 February 1999 / Accepted in revised form: 3 March 2000     

支链氨基酸代谢紊乱对2型糖尿病小鼠心肌缺血/再灌注损伤的影响

目的 探讨支链氨基酸(branched chain amino acids,BCAA)代谢紊乱对2型糖尿病（type 2 diabetes mellitus,T2DM）小鼠心肌缺血/再灌注（myocardial ischemia/reperfusion,MI/R）损伤的影响。 方法 采用高脂饮食喂养结合小剂量链脲佐菌素（STZ）腹腔注射的方法建立小鼠模型。将60只雄性C57BL/6小鼠,随机分成6组:即正常对照（Control）组、T2DM组、T2DM+盐水治疗（T2DM + Vehicle）组、T2DM+支链α-酮酸脱氢酶激酶特异性抑制剂3,6-二氯-2-苯并噻吩羧酸（BT2）治疗（T2DM + BT2）组、T2DM+盐水治疗 + I/R（T2DM + Vehicle + I/R）组及T2DM + BT2治疗 + I/R（T2DM + BT2 + I/R）组。离体培养H9C2细胞,随机分为3组,分别是对照（Control）组、缺氧/复氧（hypoxia/reoxygenation,H/R）组和H/R + BT2治疗（H/R + BT2）组,并给予不同浓度的BCAA或BCKA孵育。ELISA法检测血浆、心肌及培养的细胞上清中BCAA、BCKA水平及心肌BCKD酶活性;Western blot法检测BCKDE1α、P-BCKDE1α水平;CCK-8试剂盒检测细胞活性;乳酸脱氢酶细胞毒性检测试剂盒检测LDH释放水平;超声检测小鼠左室射血分数;TTC/伊文氏兰染色法检测心肌梗死面积。 结果 ①高脂饮食结合小剂量STZ腹腔注射,成功建立T2DM小鼠模型,T2DM组胰岛素水平较Control组明显增高（P < 0.01）;②T2DM小鼠心肌BCAA代谢紊乱。T2DM小鼠血浆和心肌中BCAA、BCKA的水平均明显升高（P < 0.01）,T2DM小鼠心肌组织BCKD酶的活性明显降低(P < 0.01）,P-BCKDE1α/ BCKDE1α显著升高（P < 0.01）;③给予T2DM小鼠BT2治疗后,其BCAA代谢紊乱得到显著改善的同时减少T2DM小鼠的心梗面积（P < 0.01）;④外源性孵育高浓度BCKA时,H9C2细胞H/R损伤加重,BT2治疗能够减轻这种损伤（P < 0.05）。 结论 BCAA代谢紊乱是糖尿病MI/R损伤加重的可能原因之一,BT2可能作为纠正T2DM BCAA代谢紊乱的有效药物。     

沉香化气胶囊对糖尿病大鼠小肠ICC和肌间神经丛的影响

目的:探讨沉香化气胶囊对糖尿病(diabetes mellitus,DM)大鼠小肠Cajal间质细胞(interstitial cells of Cajal,ICC)、肌间神经丛的影响.方法:将健康♂SD大鼠分为正常对照组、DM模型组、DM模型+中药组.大鼠一次性腹腔注射(ip)链脲佐菌素(STZ,60mg/kg)造模,选取成功模型,DM模型+中药组每天给予中药灌胃,模型组和正常对照组每天给予同等容量的蒸馏水,持续灌胃4wk.所有大鼠干预4wk结束后,给予印度墨汁灌胃测定小肠传输速率,利用免疫组织化学和图像分析观察十二指肠c-Kit、突触素(synaptophysin,Syn)、蛋白基因产物9.5(protein gene product 9.5,PGP9.5)的表达.结果:灌胃4wk后,DM模型+中药组小肠传输速率均比DM模型组明显增加(71.26±5.22 vs 45.52±6.42,P<0.01),仍低于对照组(71.26±5.22 vs 80.40±7.33,P<0.05);DM模型+中药组c-Kit、突触素、PGP9.5的阳性产物面积和吸光度值均比DM模型组明显增加(443.28±24.40 vs 358.83±35.03,832.33±58.78 vs 488.83±58.56,889.17±82.75 vs 445.17±64.06,0.16±0.02 vs 0.13±0.02,0.25±0.02 vs 0.16±0.01,0.24±0.02 vs 0.15±0.01,均P<0.01),仍低于正常对照组(443.28±24.40 vs 557.28±42.35,P<0.01;832.33±58.78 vs 937.67±101.23,P<0.05;889.17±82.75 vs 1050.50±90.22,P<0.01;0.16±0.02 vs 0.18±0.02,P<0.05;0.25±0.02 vs 0.29±0.03,P<0.01;0.24±0.02 vs 0.27±0.02,P<0.01).结论:沉香化气胶囊可以促进糖尿病大鼠小肠肌间神经丛c-Kit、突触素和PGP9.5的表达,提示对受损的DM大鼠小肠ICC、肌间神经丛有部分恢复作用,从而对糖尿病大鼠的胃肠动力障碍有一定的改善效应.     

肿瘤坏死因子相关的凋亡诱导配体对2型糖尿病大鼠内皮依赖性血管舒张功能的影响

目的 观察TNF相关的凋亡诱导配体（TRAIL）对T2DM大鼠主动脉内皮依赖性血管舒张功能的影响及其可能的机制. 方法 选取4周龄雄性SD大鼠,分为正常对照组（NC,n=10）与模型组（n=40）,随机将模型组分为T2DM亚组（n=10）与TRAIL亚组（TRAIL,n=10）.TRAIL干预6周后,检测各组FPG及FIns水平,计算ISI.检测NC组与TRAIL亚组血清TRAIL水平.观察大鼠离体主动脉内皮依赖性血管舒张反应,并检测主动脉一氧化氮（NO）含量、内皮型一氧化氮合酶活性（eNOS）.结果 与NC组比较,T2DM亚组FPG、FIns水平升高（P＜0.01）,ISI降低（P＜0.01）,血清TRAIL水平降低（P＜0.01）;血管内皮功能失调,乙酰胆碱（Ach）引起的血管最大舒张率降低（P＜0.01）,血管中NO含量及eNOS阳性表达降低（P＜0.01或P＜0.01）.TRAIL亚组血管Ach的舒张反应改善（P＜0.01）;血管中NO含量增加且eNOS阳性表达上调（P＜0.05或P＜0.01）;FPG、FIns降低,ISI提高（P＜0.01）. 结论 TRAIL改善T2DM大鼠内皮依赖性血管舒张功能的同时,可促进具有血管保护作用的NO生成.     

胰岛素抵抗和2型糖尿病大鼠主动脉内皮功能的变化及罗格列酮的影响

目的观察罗格列酮对胰岛素抵抗（IR）和2型糖尿病大鼠胸主动脉内皮依赖性舒张功能和一氧化氮（NO）的影响。方法SD大鼠高脂高糖喂养建立IR模型,链脲佐菌素（STZ）腹腔注射建立2型糖尿病大鼠模型,各模型又分为对照组和治疗组：IR对照（IRC）组、IR治疗（IRT）组、糖尿病对照（DMC）组和糖尿病治疗（DMT）组,另选正常大鼠为正常对照（NC）组和正常治疗（NT）组,治疗组用罗格列酮干预8周。检测各组大鼠空腹血糖（FPG）、空腹胰岛素（FINS）、甘油三酯（TG）和胆固醇（TC）水平,用正常葡萄糖高胰岛素钳夹技术的葡萄糖输注率（GIR）评价IR,观察大鼠离体主动脉乙酰胆碱依赖性血管舒张功能和NO浓度的变化。结果IRC、DMC组大鼠体质量、FINS、TG、TC及C反应蛋白（CRP）显著升高（P〈0．05）,IRT、DMT组大鼠FINS、TG及CRP降低（P〈0．01）;IRC、DMC组大鼠GIR、NO及各浓度的内皮依赖性舒张反应（EDVR）降低（P〈0．01）,NT、IRT和DMT组大鼠GIR、NO及ED—VR升高（P〈0．05）。EDVR与NO含量、胰岛素敏感指数（ISI）呈显著正相关（r=0．561,r=0．351）,与FPG、TG、TC及CRP呈显著负相关（r=-0．356、r=-0．451、r=-0．402、r=-0．391）。结论IR和2型糖尿病大鼠存在NO水平下降和内皮依赖性血管舒张功能紊乱,罗格列酮治疗可以升高NO水平,改善内皮功能。     

Pentoxifylline diminishes the oxidative damage to renal tissue induced by streptozotocin in the rat

Oxidative damage has been suggested to be a contributing factor in the development to diabetic nephropathy (DN). Recently, there has been evidence that pentoxifylline (PTX) has free radical-scavenging properties; thus, its anti-inflammatory and renoprotective effects may be related to a reduction in reactive oxygen species production. It is likely that the pharmacological effects of PTX include an antioxidant mechanism as shown in in vitro assays. The aim of this study was to evaluate whether the reported renoprotective effects of PTX could be the result of its antioxidant actions in streptozotocin (STZ)-induced DN in rats. The administration of PTX over a period of 8 weeks, in addition to displaying renoprotective effects, caused a significant reduction in lipoperoxide levels (LPOS) in the diabetic kidney (P < 0.05), compared to untreated rats. These levels were comparable to those in the healthy kidney of experimental animals (P > 0.05). All untreated STZ rats exhibited an increase in LPOS as opposed to healthy controls (H) (P < 0.001). The total antioxidant activity (TAA) in plasma was increased significantly already after 2 days of STZ (P < 0.05). When we examined the progression of TAA in STZ rats, there was a significant decrease over 8 weeks (P < 0.05). PTX treatment caused an increase in TAA when compared to untreated STZ rats (P < 0.05). Renal hypertrophy was less evident in PTX-treated STZ than in untreated STZ rats, evaluated by kidney weight/body weight ratio. These results indicate that PTX decreases the oxidative damage induced by these experimental procedures and may increase antioxidant defense mechanisms in STZ-induced diabetes in rats.     

Therapeutic efficacy of melatonin in reducing retinal damage in an experimental model of early type 2 diabetes in rats

Diabetic retinopathy (DR) is a leading cause of acquired blindness in adults, mostly affected by type 2 diabetes mellitus (T2DM). We have developed an experimental model of early T2DM in adult rats which mimics some features of human T2DM at its initial stages and provokes significant retinal alterations. The aim of this work was to analyze the effect of melatonin on retinal changes induced by the moderate metabolic derangement. For this purpose, adult male Wistar rats received a control diet or 30% sucrose in the drinking water. Three weeks after this treatment, animals were injected with vehicle or streptozotocin (STZ, 25 mg/kg). One day or 3 wk after vehicle or STZ injection, animals were subcutaneously implanted with a pellet of melatonin. Fasting and postprandial glycemia, and glucose, and insulin tolerance tests were analyzed. At 12 wk of treatment, animals which received a sucrose‐enriched diet and STZ showed significant differences in metabolic tests, as compared with control groups. Melatonin, which did not affect glucose metabolism in control or diabetic rats, prevented the decrease in the electroretinogram a‐wave, b‐wave, and oscillatory potential amplitude, and the increase in retinal lipid peroxidation, NOS activity, TNFα, Müller cells glial fibrillary acidic protein, and vascular endothelial growth factor levels. In addition, melatonin prevented the decrease in retinal catalase activity. These results indicate that melatonin protected the retina from the alterations observed in an experimental model of DR associated with type 2 diabetes.     

大鼠模型中糖尿病导致氯吡格雷治疗后血小板高反应性的机制研究

目的在大鼠模型中探讨糖尿病对氯吡格雷治疗后血小板高反应性(HTPR)的影响及其可能的影响机制。方法造模成功的雄性SD大鼠45只,随机分为空白组11只、氯吡格雷组11只、糖尿病组11只和糖尿病+氯吡格雷组(实验组)12只,普通饲料饲养8周,采用灌胃法给予氯吡格雷,糖尿病模型采用链脲佐菌素(STZ)一次性注射法建立。流式细胞术检测CD62P水平和细胞质内Ca2+水平,ELISA法检测同型半胱氨酸(Hcy)、高敏C反应蛋白(hs-CRP)、超氧化物歧化酶(SOD)、丙二醛(MDA)、血栓素A2(TXA2)、前列环素(PGI2)及NO等水平,RT-PCR和Westernblot检测细胞色素450(CYP450)、蛋白激酶C(PKC)及P2Y12受体基因和蛋白表达。结果糖尿病组和实验组血糖、Hcy、MDA、TXA2、hs-CRP水平、P2Y12基因和蛋白及PKC蛋白表达显著高于空白组和氯吡格雷组(P<0.01);PGI2、SOD及NO、ADP诱导的血小板聚集抑制率(ADP-IR)、CYP450蛋白表达显著低于空白组和氯吡格雷组(P<0.01)。实验组ADP-IR显著低于糖尿病组[(45.64±13.31)%vs(80.14±4.30)%,P<0.01]。糖尿病组CD62P、细胞质内Ca2+水平明显高于其他组(P<0.01);且实验组明显高于空白组和氯吡格雷组(P<0.05,P<0.01);氯吡格雷组细胞质内Ca2+水平显著低于空白组(P<0.05)。各组PKC和CYP450基因表达比较,差异无统计学意义(P>0.05)。ADP-IR与SOD和TXA2水平呈负相关(P<0.05,P<0.01);CD62P水平与细胞质内Ca2+水平呈正相关(P<0.01)。ADP-IR与CD62P水平呈负相关(r=-0.3567,P=0.015)。结论糖尿病导致氯吡格雷HTPR的机制为血小板功能异常、血小板表面受体表达上调及氯吡格雷活化相关酶系表达减少。     

Peripheral neuropathy is associated with increased serum levels of uric acid in type 2 diabetes mellitus

We assessed serum uric acid (SUA) levels in patients with type 2 diabetes mellitus (T2DM) with or without peripheral neuropathy (diagnosed by the Neuropathy Disability score [NDS]). We enrolled 64 patients with T2DM with peripheral neuropathy (group A: 31 men, mean age 63.0 ± 2.8 years) and 66 age-, gender-, renal function- and T2DM duration-matched patients without neuropathy (group B: 32 men, mean age 62.4 ± 3.1 years). Serum uric acid was significantly higher in group A (P < .001). There was a significant correlation between SUA and NDS in both groups (group A: r(s) = .93, P < .001; group B: r( s) = .95, P < .001). C-reactive protein (CRP) was also significantly higher in group A (P < .001) and correlated significantly with SUA in both groups (group A: r(s) = .93, P < .001; group B: r(s) = .87, P < .001). Serum uric acid is increased in patients with T2DM with neuropathy versus those without. Whether SUA is involved in the pathogenesis of T2DM peripheral neuropathy remains to be established.     

Microvascular blood flow responses to muscle contraction are not altered by high-fat feeding in rats

Aim: Exercise and insulin each increase microvascular blood flow and enhance glucose disposal in skeletal muscle. We have reported that insulin‐mediated microvascular recruitment in a diet‐induced model of insulin resistance (high‐fat feeding for 4 weeks) is markedly impaired; however, the effect of muscle contraction in this model has not been previously explored. Methods: We fed rats either normal (ND, 10% calories from fat) or high‐fat (HFD, 60% calories from fat) diets ad libitum for 4–8 weeks. Animals were then anaesthetized and one hindlimb electrically stimulated to contract at 0.05, 0.1 and 2 Hz (field stimulation, 30 V, 0.1 ms duration) in 15 min stepwise increments. Femoral artery blood flow (Transonic flow probe), muscle microvascular blood flow (hindleg metabolism of 1‐methylxanthine and contrast‐enhanced ultrasound) and muscle glucose disposal (uptake of radiolabelled 2‐deoxy‐d ‐glucose and hindleg glucose disappearance) were measured. Results: Both ND and HFD rats received the same voltage across the leg and consequently developed the same muscle tension. Femoral artery blood flow in the contracting leg increased during 2 Hz contraction, but not during the lower frequencies and these effects were similar between ND and HFD rats. Muscle microvascular blood flow significantly increased in a contraction frequency‐dependent manner, and preceded increases in total limb blood flow and these effects were similar between ND and HFD rats. Muscle glucose disposal was markedly elevated during 2 Hz contraction and was comparable between ND and HFD rats. Conclusion: Contraction‐mediated muscle microvascular recruitment and glucose uptake are not impaired in the HFD insulin resistant rat.     

Cardiac gene expression of natriuretic substances is altered in streptozotocin-induced diabetes during angiotensin II-induced pressure overload

OBJECTIVE: To gain insight into the cardiac adaptive mechanisms in diabetes, we studied whether angiotensin II (Ang II) alters expression of the atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and adrenomedullin (AM) genes in the left ventricle of the diabetic rat heart. METHODS: Diabetes was induced by streptozotocin (STZ; 60 mg/kg body weight intravenously). During the last 24 h of 2.5 or 7 weeks of treatment of male Wistar rats with STZ or vehicle, Ang II (33 microg/kg per h) was administered via osmotic minipumps. RESULTS: Diabetes was associated with an increased left ventricular weight to body weight (LV/BW) ratio, an index of left ventricular hypertrophy, at week 7 but not at week 2.5, and with increased ANP mRNA content at 2.5 weeks, but not with altered expression of the AM and BNP genes. Mean arterial pressure and LV/BW ratio were increased by Ang II in all groups except in the 7-week diabetic group. Levels of ANP mRNA were increased fourfold (P < 0.001) and threefold (P < 0.05) by Ang II at 2.5 and 7 weeks in control animals, respectively, and 11-fold (P < 0.001) and sevenfold (P < 0.001) at 2.5 and 7 weeks in diabetic animals, respectively. Ang II increased ventricular concentrations of BNP mRNA in control and diabetic animals at 2.5 weeks (1.3-fold, P < 0.001; and 1.6-fold, P < 0.001) and at 7 weeks (1.3-fold, P < 0.05; and 1.8-fold, P < 0.001), respectively. Left ventricular levels of adrenomedullin mRNA were increased by treatment with Ang II for 24 h in 2.5-week diabetic animals. CONCLUSION: Ang II markedly increased the levels of natriuretic peptide mRNAs in the left ventricle of normal and diabetic rat hearts, whereas it increased adrenomedullin mRNA levels only in 2.5-week diabetic rats and failed to cause hypertension in 7-week diabetic rats. Left ventricular levels of ANP and BNP mRNA were increased by Ang II in diabetic animals more than the additive effects of diabetes and Ang II alone, showing that Ang II induced an amplified response with respect to cardiac concentrations of ANP and BNP in diabetes.     

药桑不同提取物对2型糖尿病大鼠的治疗作用

目的 探讨药桑醇提物与水提物对2型糖尿病(T2DM)大鼠的治疗作用.方法 采用高脂高糖饮食同时腹腔注射链脲佐菌素复制T2DM大鼠模型.将动物随机分为模型组、拜糖平阳性对照、药桑醇提物组(20 mg/kg)和水提物组(20 mg/kg),并设置正常对照组.4 w后处死大鼠取血清测定血糖、果糖胺、血脂生化指标[总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)];取新鲜肝脏测定肝糖原、超氧化物歧化酶(SOD)、丙二醛(MDA).结果 与正常对照组比较,模型组血糖、果糖胺、MDA、TC、TG、LDL-C水平明显升高(P＜0.01),肝糖窄、HDL-C含量、SOD活性明显降低(P＜0.05).与模型组比较,药桑组各项指标有明显改善(P＜0.05).结论 药桑不同提取物可降低血糖、提高机体抗氧化能力,对T2DM大鼠具有一定的治疗作用.