Patterns of nutrient selection in rats with streptozotocin-induced diabetes

The effects of experimental diabetes on energy intake, patterns of nutrient selection, water intake, body weight and body composition were examined in male Sprague-Dawley rats given ground Purina Chow or a dietary self-selection regime. Following adaptation to dietary conditions, a portion of the animals in each diet group were made diabetic by the administration of 45 mg/kg streptozotocin (STZ). The remaining animals in each group served as vehicle-injected controls. STZ reliably produced diabetes in rats on both dietary regimes. Immediately after the induction of diabetes, rats on the self-selection regime increased carbohydrate and protein intakes and decreased fat intake. Approximately three weeks after STZ administration, diabetic rats reduced carbohydrate intake and increased fat intake. Diabetic animals in both diet groups were hyperphagic and polydipsic relative to non-diabetic controls. During the first three weeks following STZ injections, energy and water intakes of diabetic animals in the two dietary conditions were similar. However, after this initial period, energy and water intakes of diabetic rats given the self-selection regime were significantly lower than those of diabetic animals given Purina Chow.     

Low carbohydrate ketogenic diet prevents the induction of diabetes using streptozotocin in rats

Diabetes continues to be an overwhelmingly prevalent endocrine disorder that leads to several micro- and macrocomplications. It has been widely accepted that changes in dietary habits could induce or prevent the onset of diabetes. It is shown that low carbohydrate ketogenic diet (LCKD) is effective in the amelioration of many of the deleterious consequences of diabetes. However, its role in preventing the onset of diabetes is not understood. Therefore, this study is focused on the effect of LCKD in preventing the induction of diabetes using streptozotocin (STZ) in rats by biochemical and histological methods. Forty-two Wistar rats weighing 150-250 g were used in this study. The animals were divided into three groups: normal diet (ND), low carbohydrate ketogenic diet (LCKD), and high carbohydrate diet (HCD). Specific diets ad libitum were given to each group of animals for a period of 8 weeks. Each group was further subdivided into normal control, sham control and diabetic groups. Animals in the diabetic group were given a single intraperitoneal injection of STZ (55 mg/kg). All the animals were sacrificed 4 weeks after the injection of STZ. Daily measurements of food and water intake as well as weekly measurement of body weight were taken during the whole 12 weeks of the experiment. After injecting with STZ, the blood glucose level of all the groups increased significantly except for the group fed on LCKD (p value<0.01). Also, food intake, water intake and urine output were significantly increased in all groups except for the LCKD group (p value<0.01). There was also a significant decrease in the weight gain of the animals that were fed on a LCKD as compared to other groups (p value<0.05). Although, substantial decrease in the number of β cells was noticed in diabetic rats, there were no change in the number of β cells in the LCKD treated diabetic animals as compared to LCKD control group. The results presented in this study, therefore, suggests that LCKD prevents the development of diabetes using streptozotocin in rats.     

链尿佐菌素制备糖尿病神经源性膀胱大鼠模型

目的对使用单次腹腔注射大剂量链尿佐菌素（STZ）制备糖尿病神经源性膀胱大鼠模型的方法进行探讨。方法使用随机分组的方法将30只SPF级健康雄性sD大鼠随机分成正常对照组（NC组）10只、糖尿病组（DM组）20只;给予糖尿病组大鼠单次腹腔注射链尿佐菌素（60mg／kg）,同时给予对照组大鼠相同剂量的柠檬酸钠缓冲液,3d后测空腹血糖,血糖≥16．7mmol／L大鼠入选为糖尿病组模型。后观察大鼠一般指标（精神、皮毛光泽度、血糖、体重、饮食量、饮水量等）,8周时取出膀胱测残尿量、膀胱湿重、行HE染色。结果3d后糖尿病组大鼠糖尿病成模率达到90％,8周后血糖值稳定,糖尿病组膀胱HE染色有明显病理改变。DM组中糖尿病大鼠模型的糖尿病神经源性膀胱大鼠模型成模率为100％。结论通过单次大剂量腹腔注射链尿佐菌素（60mg／kg）可快速制备稳定的糖尿病大鼠模型,且在此基础上诱导神经源性膀胱大鼠模型的成功率高,在8周时其成模率可达100％。是目前一种简便、快速获取稳定糖尿病神经源性性膀胱大鼠模型的方法。     

吡格列酮对2型糖尿病大鼠肾脏及单核细胞 趋化蛋白 1表达的影响

目的：观察吡格列酮对2型糖尿病(Type 2 diabetes mellitus,T2DM)大鼠血、尿单核细胞趋化蛋白 1（monocyte chemoattractant protein 1,MCP 1）表达及肾脏组织结构和功能的影响。方法：正常对照组(NC组)喂以常规饲料;采用高糖高脂膳食、小剂量链脲佐菌素（streptozotocin,STZ）注射的方法建立2型糖尿病大鼠模型,将成模的大鼠随机分为糖尿病（DM组）和吡格列酮（PIO组）,后用吡格列酮对PIO组大鼠进行干预治疗。8周后检测血糖水平、尿生化结果、肾脏组织病理的改变情况,同时检测尿MCP 1指标的变化。结果：与NC组比较,DM组和PIO组第8周空腹血糖及糖化血红蛋白水平均明显升高,但DM组、PIO组间差异无统计学意义（P＜0.05）;第8周DM组、PIO组尿白蛋白/尿肌酐(urinary albumin／creatinine ratio,ACR)、尿视黄醇结合蛋白(urinary retinol binding protein,URBP)、尿MCP 1(urinary monocyte chemoattractant protein 1,UMCP 1)和肾脏肥大指数均高于NC组,PIO组4项指标较DM组明显降低,且UMCP 1与ACR,URBP及肾脏肥大指数呈正相关;病理显示PIO组大鼠肾小球病变程度均较DM组明显减轻,MCP 1表达减少。结论：吡格列酮对2型糖尿病大鼠肾脏有明显的保护作用,这种保护作用是独立于降糖作用之外的。其机制可能与其抑制肾组织MCP 1表达及其排泄有关。     

Dietary salt affects fluid intake and output patterns of pregnant rats

This study was done to determine how differences in dietary NaCl influence water and electrolyte balance during gestation. Eighteen adult female rats were fed diets containing either 0.12 (low), 1.0 (mid, control), or 3.0% (high) NaCl throughout gestation. On gestation days 1-19, body weight, water and food intakes, urine volume and electrolyte levels were measured. On gestation day 20, amniotic fluid electrolyte levels were determined; litter sizes were assessed 24-hr after birth. Because food intakes were similar throughout gestation, the dams of the three groups ingested different amounts of NaCl. Differences in dietary NaCl were accompanied by large differences in the daily patterns of urine sodium, urine sodium/potassium ratios, water intake, and urine volume. Despite these differences in intake and output, water and electrolyte balance (intake minus output) was the same for the three groups. There were no differences in the dams' body weights, amniotic fluid electrolyte levels, or litter sizes. The long-term consequences of perinatal dietary NaCl for the developing pups are discussed.     

葡萄籽原花青素通过Nrf2调节糖尿病大鼠肾组织GSTM的表达

目的: 研究葡萄籽原花青素(GSP)对糖尿病大鼠肾保护作用的分子生物学机制,为GSP治疗糖尿病肾病提供实验依据。方法: 雄性Wistar大鼠尾静脉注射0.1%链脲佐菌素(STZ)建立糖尿病大鼠模型,成模后随机分为糖尿病组(DM组)和糖尿病GSP治疗组(GSP组,GSP 250 mg·kg^-1·d^-1),另设正常对照组(C组)。观察24周后测量大鼠体重、收缩压、肾重/体重和24 h尿蛋白定量;采血测定空腹血糖(FPG)、尿素氮(BUN)、肌酐(SCr)和糖基化血红蛋白(HbA1c);观察糖尿病大鼠肾脏病理改变,并应用Western blotting和免疫组化法测定肾组织谷胱甘肽S-转移酶μ亚型(GSTM)和核因子E2相关因子2(Nrf2)的表达。结果: 实验开始时3组大鼠体重无明显差异(P>0.05),24周时DM组大鼠较C组大鼠体重显著下降(P<0.01),治疗后GSP组大鼠体重较DM组增加,但无显著差异(P>0.05)。第24周时DM组大鼠与C组相比较,收缩压、FPG、HbA1c、肾重/体重、24 h尿蛋白定量、BUN和SCr水平显著升高(P<0.01)。治疗后GSP组大鼠与DM组比较FPG和HbA1c水平降低,但无显著差异(P>0.05),收缩压、24 h尿蛋白定量和肾重/体重显著降低,(P<0.01),BUN和SCr水平显著降低(P<0.05)。GSP组肾组织病理改变较DM组改善。GSTM和Nrf2表达在DM组表达较C组上调,在GSP组治疗后回调(P<0.05)。结论: GSP可能通过Nrf2下调GSTM表达而起肾保护作用。     

糖尿病大鼠肾小管骨调素和p38MAPK表达的动态研究

目的:动态观察骨调素（OPN）在链脲佐菌素（STZ）诱导的糖尿病大鼠肾小管的表达，探讨它与p38丝裂原活化蛋白激酶（p38MAPK）、核转录因子-κB（NF-κB）及肾损害之间的关系。方法：雄性SD大鼠，注射STZ诱导糖尿病（DM），随机分成5组，每组分别设鼠龄匹配的正常对照组。免疫组化方法检测肾小管OPN、p38MAPK、NF-κB及纤连蛋白（FN）的表达；Western印迹法检测肾皮质OPN和p38MAPK蛋白质水平；生化方法测定血糖、血肌酐及24 h尿蛋白量；光镜检查肾组织的形态改变。结果： Western印迹和免疫组化检测发现糖尿病3 d大鼠肾组织p38MAPK和DM 7 d OPN的表达增多，并随病程发展而增加，与正常对照组比较有显著差异（P<0.01）。DM 4周，肾小管OPN的表达与p38MAPK、NF-κB、FN表达及蛋白尿呈显著正相关。结论： 糖尿病大鼠肾小管OPN表达增加参与了糖尿病肾小管间质损害的发病机制；肾小管p38MAPK可能介导了DM状态时NF-κB的表达，进而调节OPN的表达增多。     

Selection of protein and fat by diabetic rats following separate dilution of the dietary sources

Diabetic and normal rats were allowed to select their diets from separate sources of protein, carbohydrate and fat. Following the determination of baseline intakes, diabetic and normal rats received dietary components in which either the protein (Experiment 1) or fat source (Experiment 2) was diluted by 25% or 50% by the addition of cellulose. Diabetic rats failed to maintain protein intake at both dilution levels, but made up for the loss of protein-derived calories by consuming more fat. Diabetic rats maintained fat intake at both dilution levels. Dietary dilutions had no effect on total caloric intakes or body weight gain of diabetic rats. Diabetic status, measured by fasting plasma glucose levels and urinary glucose excretion rates, also was unaffected by diet dilutions. These data suggest that diabetic rats maintain total caloric intake following dilution of either the protein or fat source of their diets, but defend intake of fat-derived calories more readily than protein-derived calories. Normal rats maintained both protein and fat intake at the 25% but not at the 50% dilution level. These findings are discussed in terms of the ability of diabetic rats to solve the metabolic problems associated with their diabetic condition.     

糖尿病肾损害大鼠血清抗血管紧张素Ⅱ1型受体自身抗体水平变化

目的:观察糖尿病(DM)大鼠血清抗血管紧张素Ⅱ1型受体自身抗体(AT1-AA)与其肾损害的关系。方法:Wistar雄性大鼠36只,其中29只采用腹腔注射链脲左菌素(STZ)法成功复制DM模型(DM组),另7只用作对照(N组)。16周后,应用ELISA检测两组大鼠血清AT1-AA水平,根据检测结果将DM组AT1-AA阳性大鼠定为A组,AT1-AA阴性大鼠定为B组,测定各组大鼠血糖、24h尿白蛋白排泄率(UPE)、血尿素氮(BUN)、血肌酐(Scr)水平。结果:DM组大鼠中分布于A组11只(37.93%),分布于B组18只(62.07%),N组大鼠中有2例AT1-AA阳性(28.57%)。DM组AT1-AA阳性率明显高于N组(P<0.05);A组UPE、BUN及Scr水平均高于B组(P<0.01)。结论:自身免疫机制可能参与了DM肾损害的发生。     

Tocotrienols-rich diet decreases advanced glycosylation end-products in non-diabetic rats and improves glycemic control in streptozotocin-induced diabetic rats

This study determined the effects of palm vitamin E (TRF) diet on the levels of blood glucose, glycated hemoglobin (gHb), serum advanced glycosylation end-products (AGE) and malondialdehyde (MDA) of diabetic Sprague-Dawley rats. The rats received either control (normal rat chow), TRF diet (normal chow fortified with TRF at 1 g/kg) or Vitamin C diet (vitamin E-deficient but contained vitamin C at 45 g/kg). The animals were maintained on the respective diet for 4 weeks, made diabetic with streptozotocin (STZ), then followed-up for a further 8 weeks. At week-4, mean serum AGE levels of rats given TRF diet (0.7 +/- 0.3 units/ml) were significantly lower than those of control or Vitamin C diet rats (p pounds 0.03). The levels increased after STZ and became comparable to the other groups. At week 12, blood glucose (20.9 +/- 6.9 mM) and gHb (10.0 +/- 1.6%) of rats on TRF diet remained significantly low compared to that of control or Vitamin C diet rats (p pounds 0.03). MDA however, was not affected and remained comparable between groups throughout the study. This study showed that TRF may be a useful antioxidant; effectively prevented increase in AGE in normal rats, and caused decrease in blood glucose and gHb in diabetic rats. Further studies are needed to elucidate the mechanisms of action of TRF.     

Perinatal exposure to a high NaCl diet increases the NaCl intake of adult rats

To determine the effect of differences in perinatal NaCl exposure on NaCl intake, adult Sprague-Dawley female rats were maintained on diets containing either 0.12, 1.0, or 3% NaCl throughout pregnancy and lactation. The offspring were continued on the these same diets to 30 days postpartum. Thereafter, all offspring were fed the same basal diet containing 1% NaCl. At 90 days of age, the adult offspring were placed in metabolism cages for 7 days and fed 1% NaCl chow for days 1-2, and 0% NaCl chow for days 3-7. On days 6-7, the animals were free to consume both water and 0.3 M NaCl. When dietary NaCl was available, adult rats exposed perinatally to the high NaCl diet excreted significantly more sodium on days 1-2 and 6-7 than did the rats exposed to either the mid or low NaCl diets. There were no differences in sodium excretion during sodium deprivation on days 3-5. The 0.3 M NaCl intake of the high NaCl-exposed rats was also significantly greater than the intake of the mid and low NaCl-exposed rats. In another group of adult rats, exposed perinatally to either a low or high NaCl diet, the spontaneous 24-hr intake of water and 0.3 M NaCl was measured after repeated episodes of acute sodium depletion. Sodium depletion was induced by 48 hr of dietary sodium deprivation combined with a single subcutaneous injection of 5 mg furosemide. Acute sodium depletion was found to augment existing differences in NaCl intake between low and high NaCl-exposed rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

MiR-146a-5p对高脂饮食/链脲佐菌素诱导的糖尿病肾病大鼠肾组织的保护作用

目的:探究miR-146a-5p对高脂饮食(HFD)和链脲佐菌素(STZ)诱导的糖尿病肾病(DN)大鼠肾的保护作用及其作用机制.方法:SD大鼠随机分为正常对照组、模型组、miR-146a-5p阴性对照组(mimic对照组)和miR-146a-5p mimic处理组(mimic处理组).测量各组大鼠体质量及最后24 h饮...     

吡格列酮对DM2大鼠肝脏及MCP-1表达的影响

目的:观察吡格列酮对2型糖尿病(Type 2 diabetes mellitus,DM2)大鼠血、尿单核细胞趋化蛋白-1(monocyte chemoattractant protein-1,MCP-1)表达及肝脏组织结构和功能的影响。方法:正常对照组(NC组)以普通饲料喂养;DM2 SD大鼠模型采用高糖高脂饲料喂养联合小剂量链脲佐菌素(streptozotocin,STZ)注射的方法建立。将模型组大鼠随机分为糖尿病组(DM组)和吡格列酮组(PIO组),后者采用吡格列酮对PIO组大鼠进行干预治疗。8周后检测血糖、糖化血红蛋白(HbA1c)水平、生化指标及肝脏组织病理的改变情况,同时检血、尿MCP-1水平、尿白蛋白/尿肌酐(urinary albumin/creatinine ratio,ACR)、尿视黄醇结合蛋白(urinaryretinol binding protein,URBP)的变化。结果:与NC组比较,DM组和PIO组第8周空腹血糖及HbAlc水平均明显升高,但DM组及PIO组间差异无统计学意义(P>0.05);第8周DM组与PIO组的尿ACR、URBP、血及尿MCP-1和肝脏纤维化程度均高于NC组(P<0.05),而PIO组4项指标较DM组明显降低,且UMCP-1与ACR呈正相关;病理显示,PIO组大鼠肝脏病变程度均较DM组明显减轻,肝组织MCP-1表达减少。结论:吡格列酮对DM2大鼠肝脏有明显的保护作用,其保护作用是独立于降糖作用之外的。其机制可能与其抑制肝组织MCP-1表达及其合成有关。     

血管内皮生长因子在糖尿病股骨头多种组织的旁分泌作用

目的 探讨血管内皮生长因子(Vascular endothelial growth factor,VEGFmRNA)对糖尿病股骨头不同组织的旁分泌作用.方法建立速发型链脲佐菌素(streptozotocin,STZ)糖尿病大鼠模型,随机分为正常5周组(CON1)、10周组(CON2)及15周组(CON3),糖尿病5周组...     

Changes in salt intake after abdominal vagotomy: Evidence for hepatic sodium receptors

Several reports have suggested that the mammalian liver contains neural receptors, innervated by the vagus nerve, that monitor the sodium concentration and osmolarity of the portal circulation. These reports have been concerned primarily with either the neurophysiological identification of these receptors or their role in the short term control of urine output. Inasmuch as relatively little is known about the role of these receptors to consummatory behavior, we investigated the effects of hepatic vagotomy in rats on sodium intake as well as on sodium output. Hepatic vagotomized (HV) rats drank less NaCl solution (0.03, 0.1, 0.3M) in 24 hr during a two-bottle test with water than sham operated rats. Comparable differences in the intakes of either water, KCl or glucose solutions were not found. The two groups of rats did not differ in their intakes of water or 0.3M NaCl after an injection of either an osmotic load (IP, 2 M NaCl, 1% BW), deoxycorticosterone acetate (SC, 5 mg) along with furosemide (SC, 10 mg), or after 10 days of sodium deprivation. Urinary sodium output was reduced in HV rats during sodium deprivation but not when the rats had adequate levels of sodium in their diet. Because circadian patterns of water and food intake as well as body weight growth of hepatic vagotomized rats were similar to those of control rats, general malaise due to surgery and generalized deficits in motivation were ruled out as explanations for the depressed daily drinking of NaCl solutions. These findings support the existence of hepatic sodium receptors and their possible involvement to the control of sodium regulation.     

Differential effects of estradiol on drinking by ovariectomized rats in response to hypertonic NaCl or isoproterenol: Implications for hyper- vs. hypo-osmotic stimuli for water intake

We examined the effects of estradiol on behavioral responses to osmotic challenges in ovariectomized (OVX) rats to test the hypothesis that estradiol enhances sensitivity to gradual changes in plasma osmolality (pOsm) in stimulating water intake. Despite comparably elevated pOsm after a slow infusion of 2 M NaCl, the latency to begin water intake was significantly less in estradiol-treated OVX rats compared to that in oil vehicle-treated rats. Other groups of OVX rats were injected with isoproterenol, which increases circulating angiotensin II. These rats then were given 0.15 M NaCl to drink instead of water, to prevent decreased pOsm associated with water ingestion. Isoproterenol stimulated 0.15 M NaCl intake by both groups; however, estradiol-treated rats consumed less 0.15 M NaCl than did oil-treated rats, findings that are similar to those reported when estradiol-treated rats consumed water. The estradiol enhancement of sensitivity to increased, but not to decreased, pOsm suggests that estradiol has directionally-specific effects on osmoregulatory drinking. Moreover, the estradiol attenuation of 0.15 M NaCl intake after isoproterenol suggests that estradiol effects on osmoregulatory drinking are independent of those on volume regulatory drinking.     

Effect of long-term administration of somatostatin analogue on renal enlargement in uninephrectomized-diabetic rats.

Recent study has demonstrated that the long-acting somatostatin analogue administration effectively prevented initial renal growth in diabetic and uninephrectomized rats. In the present study we examined long-term effect of somatostatin analogue (Sandostatin) on renal enlargement in uninephrectomized-diabetic rat5. Animals were divided into 4 groups: (1) normal control rats (C) (n = 7), (2) uninephrectomized rats (NPX) (n = 7), (3) uninephrectomized-diabetic rats (NPX + DM) (n = 7) and (4) NPX + DM rats treated with Sandostatin (NPX + DM + Tx) (n = 9). All animals had free access to diet (50% protein) and water during the experimental period. To the NPX + DM + Tx rats, 2.5 micrograms of Sandostatin was given subcutaneously twice a day for 8 weeks. Periodic observations were done at 0, 4 and 8 weeks. After 8 weeks. NPX rats (0.540 +/- 0.017 (SEM)) had higher fractional kidney weights (FKW) (wet kidney wt/body wt) compared to C rats (0.410 +/- 0.014) (p < 0.0005), and both NPX + DM rats (0.983 +/- 0.098) and NPX + DM + Tx rats (1.091 +/- 0.042) had higher FKW compared to C rats (p < 0.0001) and NPX rats (p < 0.005), respectively. But no significant change of FKW was observed between NPX + DM rats and NPX + DM + Tx rats. Systolic blood pressure, BUN, serum creatinine, glomerular filtration rate and 24 hour urine protein excretion in NPX + DM rats were not different from those in NPX + DM + Tx rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ⅰ型糖尿病大鼠模型制备经验

目的探讨Ⅰ型糖尿病大鼠模型制作方法和注意事项。方法一次性大剂量注射链脲佐菌素（STZ）诱导Ⅰ型糖尿病大鼠模型。结果一般情况观察：大鼠多饮、多食、多尿、消瘦明显。体重：实验组在1、2、4、8、12周和对照组同期组比较有显著差异（P〈0.05）;实验组内1、2、4、8、12周两两比较有显著差异（P〈0.05）。尾静脉血糖：实验组在1、2、4、8、12周和对照组同期组比较有显著差异（P〈0.05）;实验组诱导前与1、2、4、8、12周比有显著差异（P〈0.05）。结论通过腹腔一次大剂量注射STZ（55mg/kg）可以严重损伤胰岛,引起与Ⅰ型糖尿病相似的症状。     

Sodium appetite in lactating rats

Lactating rats that were given free access to sodium-deficient food, water, and 0.51 M NaCl solution showed no evidence of sodium appetite. The estimated daily loss of 1-2 mEq Na in milk was replaced by basal daily intake of 2-5 ml of saline. Sodium loss in urine was minimal, but milk sodium concentration was unchanged, and pups grew normally. Saline intake was enhanced when lactating rats that had been maintained on standard laboratory chow were injected with 30% polyethylene glycol solution to reduce plasma volume but no more so than when virgin female rats or male rats were similarly colloid-treated. Lactating rats markedly increased their intake of NaCl solution after simply depriving them of dietary sodium for 4 days, whereas male and virgin female rats did not. These findings indicate that pronounced sodium appetite does not invariably accompany lactation in rats, although it can occur whenever such animals become hypovolemic or sodium deficient.