课题基金 / 基金详情

Renal Sodium Transport in the Obese Zucker Rat

Renal Sodium Transport in the Obese Zucker Rat
肥胖 Zucker 大鼠的肾钠转运
批准号:
7340799
负责人:
Carolyn Mary Ecelbarger
金额:
$2.33万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2003
资助国家:
美国
项目状态:
已结题
起止时间:
2003-06-01 至 2008-05-31

项目摘要

项目成果

Carolyn Mary Ecelbarger的其他基金

相似基金

相关文献

中文摘要
翻译
肥胖和胰岛素抵抗与高血压有关。不适当地保留钠 肾脏可能起主要作用。我们之前证明了肥胖的Zucker大鼠(这些动物的模型 疾病)增加了肾脏三种主要钠转运蛋白的蛋白丰度:α-1 Na-K-ATPase的亚基,对硫氮化物敏感的NaCI共转运体(NCC或TSC)和 上皮钠通道(ENaC)。相反,随着年龄的增长,肥胖大鼠出现肾脏肥大 与糖尿病患者相比,许多重要的盐和水运输蛋白相对减少 年龄匹配的对照组。我们认为钠中几种重要激素系统的失调 平衡可能在钠转运蛋白表达的改变以及快速 肾病的发生发展。候选系统包括肾素-血管紧张素-醛固酮系统(RAAS)和 胰岛素(和/或胰岛素抵抗)。我们假设主要钠转运蛋白的失调 肥胖的Zucker大鼠的肾脏随着年龄的增长,至少部分是由于RAAS活性的增加,以及 高胰岛素血症,两者结合在一起,会导致不适当的钠滞留和血液升高 压力。我们的具体目标包括:1)确定血管紧张素II ATLA受体的表达、结合和 肥胖的Zucker大鼠的活性上调以及这种上调是否在肾脏的变化中起作用 钠转运体调节、血压和肾脏肥大;2)确定是否增强 盐皮质激素受体(MR)活性在小鼠全肾蛋白丰度增加中起作用 在肥胖的Zucker大鼠中,对硫氮化物敏感的NaCI协同转运体(NCC)、血压和肾脏肥大; 3)测定肥胖Zucker大鼠肾脏胰岛素受体的细胞定位和敏感性。 4)确定用PPAR-γ激动剂治疗胰岛素抵抗是否会 降低NCC、β-ENaC和Na-K-ATPase的相对肾脏蛋白丰度,并减少血液 肥胖的Zucker大鼠的血压和肾脏肥厚,以及这些影响是否被Short-Th逆转 定期胰岛素输注。这些研究将使我们能够确定每一种潜力的重要性 钠转运体表达、钠平衡和血液调节失调的激素系统 这些肥胖大鼠体内的压力。
英文摘要
Obesity and insulin resistance are associated with hypertension. Inappropriate retention of sodium by the kidney is likely to play a major role. We previously showed that the obese Zucker rat (a model for these disorders) have increased renal protein abundance for three major sodium transport proteins: the alpha-1 subunit of Na-K-ATPase, the thiazide-sensitive NaCI cotransporter (NCC or TSC) and the beta-subunit of the epithelial sodium channel (ENaC). In contrast, as, they aged, obese rats developed renal hypertrophy along with diabetes and had a relative decrease in many important salt and water transport proteins, as compared to age-matched controls. We suggest that dysregulation of several important hormone systems in sodium balance may play a role in both alterations in sodium transport protein expression, as well as, the rapid develop of nephropathy. Candidate systems include the renin-angiotensin-aldosterone system (RAAS) and insulin (and or insulin resistance). We hypothesize that dysregulation of major sodium transport proteins of the kidney in the obese Zucker rat with age, is due at least in part to increased RAAS activity, and hyperinsulinemia, which in combination, result in inappropriate sodium retention and elevated blood pressure. Our specific aims include: 1) to determine if angiotensin II ATla receptor expression, binding, and activity is upregulated in the obese Zucker rat and whether this upregulation plays a role in changes in renal sodium transporter regulation, blood pressure, and renal hypertrophy; 2) to determine if enhanced mineratocorticoid receptor (MR) activity plays a role in increased whole kidney protein abundance of the thiazide-sensitive NaCI cotransporter (NCC), blood pressure, and renal hypertrophy, in the obese Zucker rat; 3) to determine the cellular location and sensitivity of the renal insulin receptor in obese Zucker rats relative to lean age-mates; 4) to determine whether treatment of insulin resistance with a PPAR-gamma agonist will decrease relative renal protein abundance of NCC, beta-ENaC, and Na-K-ATPase, as well as reduce blood pressure and renal hypertrophy in the obese Zucker rat, and whether these effects are reversed with short- term insulin infusion. These studies will allow us to determine the importance of each of these potential regulatory hormone systems in dyregulation of sodium transporter expression, sodium balance, and blood pressure in these obese rats.
期刊论文(22)
专著(0)
科研奖励(0)
会议论文
DOI: 10.1016/s1550-8579(06)80219-6
发表时间: 2006-12-01
期刊: Gender medicine
影响因子: --
作者: [Riazi, Shahla, Madala-Halagappa, Veerendra K, Ecelbarger, Carolyn A]
通讯作者: Ecelbarger, Carolyn A
Sex and age result in differential regulation of the renal thiazide-sensitive NaCl cotransporter and the epithelial sodium channel in angiotensin II-infused mice.
性别和年龄导致血管紧张素 II 输注小鼠肾噻嗪类敏感 NaCl 协同转运蛋白和上皮钠通道的差异调节。
DOI: 10.1159/000252776
发表时间: 2009
期刊: American journal of nephrology
影响因子: 4.2
作者: [Tiwari,Swasti, Li,Lijun, Riazi,Shahla, Halagappa,VeerendraKMadala, Ecelbarger,CarolynM]
通讯作者: Ecelbarger,CarolynM
Chronic rosiglitazone therapy normalizes expression of ACE1, SCD1 and other genes in the kidney of obese Zucker rats as determined by microarray analysis.
通过微阵列分析确定,长期罗格列酮治疗可使肥胖 Zucker 大鼠肾脏中 ACE1、SCD1 和其他基因的表达正常化。
DOI: 10.1055/s-2008-1042429
发表时间: 2008
期刊: Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association
影响因子: --
作者: [Song,J, Liu,H, Ressom,HW, Tiwari,S, Ecelbarger,CM]
通讯作者: Ecelbarger,CM
DOI: 10.1016/j.phrs.2008.03.013
发表时间: 2008-05
期刊: Pharmacological research
影响因子: 9.3
作者: [Swasti Tiwari;E. Blasi;J. Heyen;A. Mcharg;C. Ecelbarger]
通讯作者: Swasti Tiwari;E. Blasi;J. Heyen;A. Mcharg;C. Ecelbarger
12
    Role of Insulin Receptors in the Kidney
    • 批准号:
      8293359
    • 项目类别:
    • 资助金额:
      $32.75万
    • 财政年份:
      2010
    • 负责人:
      Carolyn Mary Ecelbarger
    • 依托单位:
    Role of Insulin Receptors in the Kidney
    • 批准号:
      8072593
    • 项目类别:
    • 资助金额:
      $31.15万
    • 财政年份:
      2010
    • 负责人:
      Carolyn Mary Ecelbarger
    • 依托单位:
    Role of Insulin Receptors in the Kidney
    • 批准号:
      7887108
    • 项目类别:
    • 资助金额:
      $37.9万
    • 财政年份:
      2010
    • 负责人:
      Carolyn Mary Ecelbarger
    • 依托单位:
    Role of Insulin Receptors in the Kidney
    • 批准号:
      8484832
    • 项目类别:
    • 资助金额:
      $30.43万
    • 财政年份:
      2010
    • 负责人:
      Carolyn Mary Ecelbarger
    • 依托单位:
    国内基金
    海外基金
    补阳还五汤通过AGE-RAGE通路调控脓毒症免疫失衡的机制与转化研究
    靶向递送一氧化碳调控AGE-RAGE级联反应促进糖尿病创面愈合研究
    • 批准号:
      JCZRQN202500010
    • 项目类别:
      省市级项目
    • 资助金额:
      --
    • 批准年份:
      2025
    • 负责人:
    • 依托单位:
    对香豆酸抑制AGE-RAGE-Ang-1通路改善海马血管生成障碍发挥抗阿尔兹海默病作用
    • 批准号:
      2025JJ70209
    • 项目类别:
      省市级项目
    • 资助金额:
      --
    • 批准年份:
      2025
    • 负责人:
      雷芬芳
    • 依托单位:
    AGE-RAGE通路调控慢性胰腺炎纤维化进程的作用及分子机制
    • 批准号:
      --
    • 项目类别:
      面上项目
    • 资助金额:
      --
    • 批准年份:
      2024
    • 负责人:
      万荣
    • 依托单位: