Influence of streptozotocin and alloxan induced diabetes on the metabolism of dermal collagen in albino rats

Summary The metabolism of collagen in male rats made diabetic by treatment with either streptozotocin or alloxan was studied after the injection of³H-proline by estimating specific and total³H-hydroxyproline activity in skin collagen fractions and urine. Experimentally induced diabetes was found to decrease the neutral salt-soluble and acid-soluble collagen with no change in insoluble collagen as compared to a control group. The specific and total radioactivity of³H-hydroxyproline in soluble and insoluble collagen fractions were also decreased. Studies of total³H-hydroxyproline activities in soluble collagens and insoluble collagen showed that the conversion of soluble to insoluble collagen was influenced by diabetes. Both streptozotocin and alloxan were found to increase urinary excretion of total hydroxyproline and³H-hydroxyproline during the first 12 h after the administration of³H-proline. Weekly analyses of urinary hydroxyproline also indicated a similar pattern. The results of the present investigation clearly indicate decreased synthesis and increased catabolism of collagen accompanied by accelerated conversion of soluble to insoluble collagen in experimentally induced diabetes.     

Protective effect of probucol on alloxan diabetes in rats

The diabetogenic action of alloxan is known to be attenuated by several oxygen radical scavengers. The present study was conducted to see if probucol, a drug with strong free radical scavenger action, can reduce pancreatic B-cell damage induced by alloxan in male Wistar rats. After 2 weeks of a 1% probucol diet, 50 mg/kg alloxan was intravenously injected in rats (group PA, n = 34). Urine glucose of most of the injected rats not pretreated with probucol (group A, n = 22) was positive, while more than half of the rats of group PA failed to show urine glucose. The blood glucose level in group PA was significantly lower than that in group A (326 +/- 25 vs. 487 +/- 28 mg/dl, P less than 0.001). Histological examination revealed that most of the pancreatic islets of group A were degranulated, whereas a lot of islets remained unaffected in group PA. Thus, the in vivo diabetogenic action of alloxan was reduced by pretreatment with probucol, although the effect was incomplete. This effect can be explained by probucol's strong free radical scavenger action. Since accumulation of free radicals can be an initial step of B-cell damage in animal models of type 1 (insulin-dependent) diabetes, the drug can be useful for the prevention of type 1 diabetes with its long-term clinical history of safety.     

Hypoglycemic potential of nateglinide versus glyburide in patients with type 2 diabetes mellitus

Antidiabetic agents that augment insulin secretion can cause hypoglycemia. With the current trend toward early and aggressive treatment of patients with type 2 diabetes, the hypoglycemic potential of insulinotropic agents is of concern. This study aimed to compare the propensity of the "glinide," nateglinide, and the sulfonylurea (SU), glyburide, to elicit hypoglycemia in type 2 diabetic patients with moderately elevated fasting plasma glucose (FPG). Hyperglycemic clamps (target plasma glucose = 11.1 mmol/L) were initiated, and 30 minutes later patients received a single oral dose of nateglinide (120 mg, n = 15) or glyburide (10 mg, n = 12) in a double-blind fashion. At the end of the 2-hour clamp when the glucose infusion was terminated, plasma glucose and insulin levels were measured for 4 additional hours. The minimum plasma glucose level achieved after terminating the glucose infusion (glucose nadir) was used as an index of hypoglycemic potential. The mean (+/-SEM) glucose nadir was significantly lower in patients given glyburide (3.3 +/- 0.2 mmol/L) versus nateglinide (4.4 +/- 0.3 mmol/L, P = .025). Confirmed hypoglycemia (plasma glucose < or = 2.8 mmol/L) occurred in 2 of 12 patients given glyburide and in none of those given nateglinide. Plasma insulin levels were significantly higher from 100 to 240 minutes after clamp termination in patients given glyburide versus nateglinide. Nateglinide has less hypoglycemic potential than glyburide, suggesting that nateglinide may be a more appropriate insulinotropic agent for patients with moderate fasting hyperglycemia, such as elderly patients and those with comorbid cardiac ischemia.     

盐酸丁咯地尔治疗2型糖尿病疗效观察

目的　观察盐酸丁咯地尔对糖尿病患者血粘度、红细胞变形能力、血小板聚集功能、血糖及胰岛素敏感性的影响。方法　 6 4例 2型糖尿病患者在保持原有饮食、运动、药物不变基础上随机分为两组 ,治疗组给予盐酸丁咯地尔 2 0 0 mg/d,静脉滴注 14天 ,对照组给予维生素 C、维生素 B6 静脉点滴。结果　应用盐酸丁咯地尔治疗后全血粘度、红细胞变形能力、血小板聚集功能、血糖、 Hom a- IR指数均明显改善 (P <0 .0 5～ 0 .0 1)。结论　盐酸丁咯地尔能显著改善 2型糖尿病患者血粘度、红细胞变形能力、血小板聚集功能 ,能增加胰岛素敏感性 ,有显著的协助降糖作用 ,并可能影响糖尿病患者的亚临床炎症状态。     

Amelioration of alloxan induced diabetes mellitus and oxidative stress in rats by oil of Eruca sativa seeds

Clinical research has confirmed the efficacy of several plant extracts in the modulation of oxidative stress associated with diabetes mellitus (DM). Oil of Eruca sativa seeds (ESS) is tried for prevention and treatment of DM induced experimentally by alloxan injection. A single dose of alloxan (100 mg/kg) produced a decrease in insulin level, hyperglycemia, elevated total lipids, triglycerides and cholesterol, decreased high-density lipoprotein and hepatic glycogen contents and elevated hepatic glucose-6-phosphatase activity. Concurrent with these changes, there was an increase in the concentration of malondialdehyde and 4-hydroxynonenal in the liver. This oxidative stress was related to a decreased glutathione (GSH) content and superoxide dismutase activity in the liver of alloxan-diabetic rats. ESS oil (0.06 ml/kg) on its own increased significantly hepatic GSH. Daily oral administration of ESS oil 2 weeks before or after diabetes induction ameliorated hyperglycemia, improved lipid profile, blunted the increase in malondialdehyde and 4-hydroxynonenal and stimulated the GSH production in the liver of alloxan-treated rats. We suggested that ESS oil could be used as antidiabetic complement in case of DM. This may be related to its antioxidative properties and to the increase in hepatic GSH.     

Lipid-lowering effect of simvastatin in patients of type 2 diabetes mellitus.

BACKGROUND: Dyslipidemia is an important factor in causation of macrovascular disease in type 2 diabetics. The role of simvastatin in the management of dyslipidemia in patients with type 2 diabetes mellitus is not very well elucidated, particularly in the context of the recent American Diabetes Association criteria 2001. The American Diabetes Association suggests that aggressive therapy of diabetic dyslipidemia will reduce the risk of coronary heart disease in diabetics and that optimal levels are serum low-density lipoprotein cholesterol <2.60 mmol/L (< 100 mg/dl), high-density lipoprotein cholesterol >1.1 5 mmol/L (>45 mg/dl) and triglycerides <2.30 mmol/L, (<200 mg/dl).This study was planned to compare the effect of simvastatin together with behavioral modification and behavioral modification alone, in age, sex and body mass index matched patients with type 2 diabetes mellitus with dyslipidemia, in reaching the target levels of various lipids as suggested by the American Diabetes Association criteria 2001. METHODS AND RESULTS: An open-label, prospective study was conducted on 80 patients with type 2 diabetes mellitus, who had fair to moderate glycemic control with a total glycated hemoglobin < 10%. The patients in the control group (n=40) were treated with only behavioral modifications like calorie control and daily walking for 30 minutes, and no lipid-lowering agent was given. The lipid profile was re-evaluated after 6 and 12 weeks. The patients in the test group (n=40) were advised behavioral modification and given simvastatin. The starting dose was 10 mg at bed time. After 6 weeks of simvastatin therapy, a lipid profile was done. If the goal of low-density lipoprotein cholesterol < 100 mg/dl and/or triglycerides <200 mg/dl and/or high-density lipoprotein cholesterol >45 mg/dl was not achieved, the dose of simvastatin was increased to 20 mg at bedtime for another 6 weeks. It was observed that low-density lipoprotein dyslipidemia was most prevalent. In the control group, a favorable alteration in lipid levels was brought about but none was statistically significant and the American Diabetes Association goals were not achieved in any of the patients. In the test group, there was a significant and favorable alteration in all lipid moieties, and the target levels were achieved in 80% of patients after 12 weeks. There was no significant alteration in glycemic control and liver functions. Myopathy and epigastric pain were seen in 1 patient in each group. CONCLUSIONS: In our study, behavioral modification alone did not achieve the target levels of various lipids in diabetic dyslipidemia as per the American Diabetes Association guidelines. Hence, pharmacological therapy with statins should be resorted to in patients with type 2 diabetes mellitus who carry a high risk of coronary heart disease. Simvastatin is a safe and efficacious lipid-lowering drug.     

2型糖尿病大鼠并发心肌病的研究

目的 在大鼠中复制类似人类2型糖尿病模型,观察并发糖尿病性心肌病的情况.方法 取健康雄性SD大鼠120只,体质量180～220 g,按体质量及血糖值分为4组:(1)糖尿病组:40只,高糖高脂饲料喂养,一次性腹腔注射30 mg/kg链脲佐菌素(STZ)溶液;(2)STZ组:30只,普通饲料喂养,一次性腹腔注射30 mg/kg STZ溶液;(3)高糖高脂饲料组:25只,高糖高脂饲料喂养,一次性腹腔注射等容积柠檬酸盐缓冲液溶液;(4)对照组:25只,普通饲料喂养,一次性腹腔注射等容积柠檬酸盐缓冲液溶液.腹腔注射STZ溶液或柠檬酸盐缓冲液溶液后,观察动物饮水、进食及尿量变化.注射后4、8、12、16周,各组分批抽样检查,称取体质量,取血检测空腹血糖、空腹胰岛素、三酰甘油、总胆固醇;处死动物取心脏称质量,取心肌组织行光镜及透射电镜观察.结果 实验饲料喂养1周,各组大鼠体质量、血糖差异无统计学意义(P>0.05);喂养4周,STZ或柠檬酸盐缓冲液注射前,糖尿病组和高糖高脂饲料组大鼠体质量、空腹胰岛素、胰岛素抵抗指数较对照组和STZ组明显升高(P<0.05);糖尿病组与高糖高脂饲料组相比、STZ组和对照组相比差异均无统计学意义(P>0.05).注射后4个时段,糖尿病组和高糖高脂饲料组大鼠血糖、体质量、心脏质量、血三酰甘油、总胆固醇比同时段的对照组和STZ组增高(P<0.05),糖尿病组大鼠的上述指标较高糖高脂饲料组大鼠增加更显著,差异有统计学意义(P<0.05),STZ组和对照组相比差异无统计学意义(P>0.05).心肌光镜和电镜检查结果显示,糖尿病组大鼠心肌细胞肥厚并出现变性、凋亡等显著病变,间质胶原纤维增生;STZ组大鼠心肌无明显病理改变;高糖高脂饲料组大鼠心肌呈现类似糖尿病大鼠病理改变,但与糖尿病组大鼠相比,改变较不明显.结论 2型糖尿病大鼠成模4周后,心脏发生糖尿病性心肌病的病理改变,表现为心肌细胞肥大、变性,间质纤维组织增生,其发生率为100%.     

Hyperglycemic crises in diabetes mellitus type 2.

Hyperglycemic crises in type 2 diabetes are not rare and are becoming increasingly recognized as part of the spectrum of the presentation of previously undiagnosed diabetes mellitus and the decompensation of established diabetes mellitus. Contributing factors and associations are being elucidated but remain far from clear, particularly in DKA states. Medications commonly used in the treatment of many comorbid illnesses in patients with diabetes can themselves predispose to HHS. Endocrinopathies can contribute to insulin resistance and directly increase the glycemic load, leading to hyperglycemia. Medications such as the protease inhibitors may in the future lead to a better understanding of the pathophysiology of the metabolic derangements seen in the development of type 2 diabetes mellitus.     

A new diabetes model induced by neonatal alloxan treatment in rats

Rats treated with streptozotocin (STZ) during the neonatal period have been used as a model of non-insulin-dependent diabetes mellitus. The present study was designed to produce another diabetes model by substituting alloxan for STZ. Male Sprague-Dawley rats of 2, 4 or 6 days of age were injected intraperitoneally with 200 mg/kg of alloxan monohydrate after 16 h fast. Control rats received vehicle alone at 6 days of age. Non-fasting plasma glucose levels in alloxan-treated rats significantly increased after 8 weeks as compared with control, as the age of alloxan treatment advanced (6.6 ± 0.2 (S.E.M.) mM in control, 8.3 ± 0.3 mM in 2 days, P < 0.05, 9.8 ± 0.9 mM in 4 days, P < 0.05, 17.1 ± 3.5 mM in 6 days, P < 0.05). For the long-term observation, alloxan-treated rats were divided into mild and severe diabetes groups. Hyperglycemia persisted in both groups until 52 weeks (6.5 ± 0.1 mM in control, 10.3 ± 0.7 mM in mild diabetes group, 25.3 ± 3.6 mM in severe group), but significant albuminuria developed only in severe diabetes group. The diabetogenicity of alloxan rapidly increased during the neonatal period, and the neonatal alloxan diabetes model may be useful for studying chronic diabetic complications.     

Therapeutic effect of okra extract on gestational diabetes mellitus rats induced by streptozotocin

Objective:To explore the effect of okra extract on gestational diabetes mellitus(GDM) rats and its probable molecular mechanism.Methods:A total of 30 female SD rats were caged with male rats for pregnancy,27 pregnant rats were obtained and weighed.The pregnant rats were equally randomized into the control group,GDM group and intervention group.Once the pregnancy was verified,GDM group and intervention group were given 45 mg/kg streptozotocin by peritoneal injection for inducing GDM,control group was given equal volume of citrate buffer.Once the model was established successfully,intervention group was administered orally the solution containing 200 mg/kg/d okra extract,the other groups were given the diet and water only.On the 19 th day of pregnancy,the blood samples and fetal rats of all groups were collected,fetal rats weight and placental weight was recorded and the serum glucose,lipids,serum insulin and C-peptide of pregnant rats before the delivery were determined.Results:The pregnant rats weight before the delivery,fetal rats weight and placental weight of GDM group were lower than control group and intervention group(P0.05).After the treatment of okra extract,serum glucose and lipids levels of intervention group were both improved significantly(P0.05),especially,the FBG,HDL,FINS,serum m insulin and hepatic glycogen levels were equivalent to control group(P0.05).Antioxidant enzymes levels of GDM group in liver and pancreas tissues were lower than the other groups,and after treatment of okra extract,antioxidant enzymes levels in liver and pancreas tissues were equivalent to control group(P0.05).Conclusions:Okra extract,rich in antioxidant substances,could avoid the excessive consuming of antioxidant enzymes,then,suppresses the oxidative stress and insulin resistance,thereby improving blood glucose level of GDM rats.     

缬沙坦对2型糖尿病大鼠心肌细胞凋亡的影响

目的探讨缬沙坦对糖尿病大鼠心肌细胞凋亡的作用。方法随机选择29只健康雄性SD大鼠中的21只,以高糖高脂饲料喂养4周后腹腔注射链脲佐菌素30mg/kg,3d后测血糖≥16.7mmol/L者（n=19）入选糖尿病大鼠模型,并随机分为糖尿病组（DM组,n=9）和缬沙坦治疗组（VAL组,n=10）,另外8只健康雄性SD大鼠为对照组（CN组,n=8）。VAL组给予缬沙坦（20mg/kg.d）治疗6周,检测各组大鼠血生化和胰岛素水平,各组大鼠于第12周末处死,取部分左心室前壁组织以TUNEL法检测大鼠心肌细胞凋亡,免疫组化法检测Caspase-3、NF-κB的表达。结果与CN组相比,DM组和VAL组大鼠心肌细胞凋亡及Caspase-3和NF-κB的阳性表达显著增多,差异具有统计学意义（P〈0.05）;与DM组相比,VAL组大鼠心肌细胞凋亡及Caspase-3和NF-κB的阳性表达明显减少,差异具有统计学意义（P〈0.05）。结论缬沙坦能够抑制糖尿病大鼠心肌细胞的凋亡,具有心肌保护作用。     

维生素D3对2型糖尿病患者血管内皮功能的保护作用

目的 探讨1,25-二羟维生素D3对2型糖尿病患者血管内皮功能的影响.方法 选取我科2009～2011年住院的2型糖尿病患者80例,随机分为治疗组和对照组各40例,在血糖稳定1周后,治疗组给予常规治疗＋骨化三醇胶丸,对照组给予常规治疗,两组患者疗程均为12周.治疗前后行内皮依赖性血管舒张功能检测,同时检测其血C反应蛋白（CRP）、白细胞介素（IL）-6水平.结果 经过12周的治疗,治疗组患者体内CRP、IL-6低于对照组（P均＜0.05）;且治疗组患者内皮依赖性血管内径变化率高于对照组（P＜0.05）.结论 维生素D3可显著改善2型糖尿病患者体内的炎症状态,并改善2型糖尿病患者血管内皮功能.     

舒洛地特对SUMO4介导的2型糖尿病大鼠肾脏的保护作用

目的：探讨舒洛地特对小泛素养修饰蛋白（SUMO）4介导的2型糖尿病大鼠肾脏功能的保护作用.方法：将20只GK大鼠按数字表法随机均分为糖尿病组（DM组）、舒洛地特治疗组（DM＋S组）,SPF级同龄雄性Wistar大鼠10只作为健康对照组,DM＋S组给予舒洛地特10mg· kg-1·d-1腹腔注射,连续8周,其余两组给予等体积生理盐水注射.分别于用药前1d和用药结束后次日测定24 h尿微量白蛋白量,光镜下观察肾脏组织的结构变化,免疫组化法检测三组大鼠肾脏组织中核转录因子-κB（NF-κB）、SUMO4、NF-κB抑制剂（IκB）的表达.结果：（1）用药前DM组与DM＋S组大鼠的血糖及24 h尿白蛋白排泄率显著高于健康对照组（P＜0.01）;用药后DM＋S组24 h尿白蛋白排泄率显著低于DM组[（146.90±10.92）％比（314.63±20.42）％,P＜0.01];（2）与健康对照组相比,光镜下GK大鼠的肾脏肾小球毛细血管球肥大,基底膜轻度增厚,肾小球系膜细胞增生、肥大,肾小管上皮细胞肥大.未见典型的结节性肾小球硬化,似为糖尿病肾损害的早期改变,DM＋S组肾脏组织病理改变较DM组明显减轻;（3）免疫组化示：DM＋S组和DM组SUMO4、NF-κB、IκB表达显著高于健康对照组;与DM组比较,DM＋S组SUMO4[（29.8±0.6）比（34.2±0.7）]、IκB[（25.5±0.7）比（37.3±0.6）]表达显著增加,NF-κB[（43.9±0.9）比（27.0±0.6）]表达显著减少,P均＜0.05.结论：（1）小泛素养修饰蛋白4、NF-κB抑制剂在糖尿病GK大鼠肾脏组织表达增多;（2）舒洛地特对糖尿病GK大鼠肾脏组织有一定的保护作用.     

Clinical science of type 2 diabetes mellitus.

Clinical Research in Diabetes and Obesity. Edited by Boris Draznin and Robert Rizza. Totowa, Humana, 1997. Volume I. Methods, Assessment and Metabolic Regulation. $139.50 (xii +396 pages), ISBN 0-89603-350-3. Volume II. Diabetes and Obesity. $139.50 (xii +392 pages), ISBN 0-89603-492-5.     

Role of vitamin D in the pathogenesis of type 2 diabetes mellitus

Vitamin D deficiency has been shown to alter insulin synthesis and secretion in both humans and animal models. It has been reported that vitamin D deficiency may predispose to glucose intolerance, altered insulin secretion and type 2 diabetes mellitus. Vitamin D replenishment improves glycaemia and insulin secretion in patients with type 2 diabetes with established hypovitaminosis D, thereby suggesting a role for vitamin D in the pathogenesis of type 2 diabetes mellitus. The presence of vitamin D receptors (VDR) and vitamin D–binding proteins (DBP) in pancreatic tissue and the relationship between certain allelic variations in the VDR and DBP genes with glucose tolerance and insulin secretion have further supported this hypothesis. The mechanism of action of vitamin D in type 2 diabetes is thought to be mediated not only through regulation of plasma calcium levels, which regulate insulin synthesis and secretion, but also through a direct action on pancreatic β-cell function. Therefore, owing to its increasing relevance, this review focuses on the role of vitamin D in the pathogenesis of type 2 diabetes mellitus.