Renal Sodium Transport in the Obese Zucker Rat
Renal Sodium Transport in the Obese Zucker Rat
批准号:
7239683
负责人:
Carolyn Mary Ecelbarger
金额:
$33.8万
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 2009-05-31
关键词:
AcuteAgeAgonistAldosteroneAngiotensin IIAngiotensin-Converting Enzyme InhibitorsAngiotensinsAutoradiographyBindingBlood PressureCanrenoneCarrier ProteinsCollagen Type IVDataDiabetes MellitusDietDisease modelDistalDown-RegulationEnalaprilEndocrineEnzymesEpithelialEquilibriumEtiologyFibronectinsGlucocorticoidsGoalsHomeostasisHormonesHyperinsulinismHypertensionHypertrophyIn SituIn Situ HybridizationIn VitroInfusion proceduresInsulinInsulin ReceptorInsulin ResistanceKidneyKidney DiseasesLaboratoriesLocationMessenger RNAMineralocorticoid ReceptorMineralocorticoidsModelingMolecularNa(+)-K(+)-Exchanging ATPaseNatriuresisObesityPPAR gammaPartner in relationshipPathologyPatternPhosphorylationPlasmaPlayProcessProtein Tyrosine KinaseProteinsRangeRattusReceptor SignalingRegulationRelative (related person)Renal HypertensionRenal tubule structureReninRenin-Angiotensin-Aldosterone SystemResearch PersonnelRoleSeriesSignal TransductionSignaling ProteinSodiumSodium ChannelSodium ChlorideSteroidsSystemTestingUp-RegulationVasopressinsWaterWeekZucker Ratsage relatedagedblood pressure regulationcandesartandaydesigndietary restrictionepithelial Na+ channelmRNA Expressionpreventprogramsprotein expressionreceptorreceptor bindingreceptor expressionresponserosiglitazonesalureticthiazidewater channel
中文摘要
描述(由申请人提供):
肥胖和胰岛素抵抗与高血压有关。肾脏对钠的不适当保留可能起主要作用。我们先前表明,肥胖Zucker大鼠(这些疾病的模型)增加了三种主要钠转运蛋白的肾脏蛋白丰度:Na-K-ATP酶的α-1亚基,噻嗪敏感性NaCl协同转运蛋白(NCC或TSC)和上皮钠通道的β亚基(ENaC)。相反,随着年龄的增长,肥胖大鼠出现肾脏肥大沿着糖尿病,与年龄匹配的对照组相比,许多重要的盐和水转运蛋白相对减少。我们认为,钠平衡中几个重要激素系统的失调可能在钠转运蛋白表达的改变以及肾病的快速发展中发挥作用。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)。我们推测,随着年龄的增长,肥胖Zucker大鼠肾脏主要钠转运蛋白的失调,至少部分是由于RAAS活性增加和高胰岛素血症,两者结合,导致不适当的钠潴留和血压升高。我们的具体目标包括:1)确定肥胖Zucker大鼠中血管紧张素II At 1a受体表达、结合和活性是否上调,以及这种上调是否在肾钠转运蛋白调节、血压和肾肥大的变化中起作用; 2)确定增强的盐皮质激素受体(MR)活性是否在噻嗪敏感性NaCl协同转运蛋白(NCC)的增加的全肾蛋白丰度中起作用,3)确定肥胖Zucker大鼠相对于瘦年龄组大鼠肾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-ATP酶的相对肾蛋白丰度,以及降低肥胖Zucker大鼠的血压和肾脏肥大,以及短期胰岛素输注是否逆转这些作用。这些研究将使我们能够确定这些潜在的调节激素系统中的每一个在这些肥胖大鼠的钠转运蛋白表达、钠平衡和血压调节异常中的重要性。
英文摘要
DESCRIPTION (provided by applicant):
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 At1a 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 mineralocorticoid 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(0)
专著(0)
科研奖励(0)
会议论文
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:
Role of Insulin Receptors in the Kidney
-
批准号:8326300
-
项目类别:
-
资助金额:$0.8万
-
财政年份:2010
-
负责人:Carolyn Mary Ecelbarger
-
依托单位:
NaCI Balance and Targeted Insulin Receptor Knockout Mice
-
批准号:6673317
-
项目类别:
-
资助金额:$14.14万
-
财政年份:2003
-
负责人:Carolyn Mary Ecelbarger
-
依托单位:
Renal Sodium Transport in the Obese Zucker Rat
-
批准号:6900324
-
项目类别:
-
资助金额:$31.04万
-
财政年份:2003
-
负责人:Carolyn Mary Ecelbarger
-
依托单位:
Insulin, Renal Sodium Transport and Blood Pressure
-
批准号:6785515
-
项目类别:
-
资助金额:$25.26万
-
财政年份:2003
-
负责人:Carolyn Mary Ecelbarger
-
依托单位:
Renal Sodium Transport in the Obese Zucker Rat
-
批准号:7073450
-
项目类别:
-
资助金额:$30.31万
-
财政年份:2003
-
负责人:Carolyn Mary Ecelbarger
-
依托单位:
Insulin, Renal Sodium Transport and Blood Pressure
-
批准号:6929844
-
项目类别:
-
资助金额:$24.87万
-
财政年份:2003
-
负责人:Carolyn Mary Ecelbarger
-
依托单位:
Renal Sodium Transport in the Obese Zucker Rat
-
批准号:6602611
-
项目类别:
-
资助金额:$29.66万
-
财政年份:2003
-
负责人:Carolyn Mary Ecelbarger
-
依托单位:
Renal Sodium Transport in the Obese Zucker Rat
-
批准号:7340799
-
项目类别:
-
资助金额:$2.33万
-
财政年份:2003
-
负责人:Carolyn Mary Ecelbarger
-
依托单位:
Renal Sodium Transport in the Obese Zucker Rat
-
批准号:6747709
-
项目类别:
-
资助金额:$31.04万
-
财政年份:2003
-
负责人:Carolyn Mary Ecelbarger
-
依托单位:
Insulin, Renal Sodium Transport and Blood Pressure
-
批准号:7103515
-
项目类别:
-
资助金额:$23.8万
-
财政年份:2003
-
负责人:Carolyn Mary Ecelbarger
-
依托单位:
Insulin, Renal Sodium Transport and Blood Pressure
-
批准号:6674786
-
项目类别:
-
资助金额:$23.88万
-
财政年份:2003
-
负责人:Carolyn Mary Ecelbarger
-
依托单位:
NaCI Balance and Targeted Insulin Receptor Knockout Mice
-
批准号:6762353
-
项目类别:
-
资助金额:$15.52万
-
财政年份:2003
-
负责人:Carolyn Mary Ecelbarger
-
依托单位:
REGULATION OF THE RENAL SALT AND WATER TRANSPORTERS
-
批准号:6380116
-
项目类别:
-
资助金额:$8.86万
-
财政年份:1999
-
负责人:Carolyn Mary Ecelbarger
-
依托单位:
REGULATION OF THE RENAL SALT AND WATER TRANSPORTERS
-
批准号:2840956
-
项目类别:
-
资助金额:$8.86万
-
财政年份:1999
-
负责人:Carolyn Mary Ecelbarger
-
依托单位:
REGULATION OF THE RENAL SALT AND WATER TRANSPORTERS
-
批准号:6176963
-
项目类别:
-
资助金额:$8.86万
-
财政年份:1999
-
负责人:Carolyn Mary Ecelbarger
-
依托单位:
RENAL TUBULAR EXPRESSION OF V-1A VASOPRESSIN RECEPTOR
-
批准号:2135715
-
项目类别:
-
资助金额:$2.76万
-
财政年份:1995
-
负责人:Carolyn Mary Ecelbarger
-
依托单位:
国内基金
海外基金
登录
查看更多内容
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
-
批准号:JCZRLH202601523
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2026
-
负责人:
-
依托单位:
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:
甜茶抑制AGE-RAGE通路增强突触可塑性改善小鼠抑郁样行为
-
批准号:2023JJ50274
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2023
-
负责人:贺志明
-
依托单位:
蒙药额尔敦-乌日勒基础方调控AGE-RAGE信号通路改善术后认知功能障碍研究
-
批准号:--
-
项目类别:地区科学基金项目
-
资助金额:33万元
-
批准年份:2022
-
负责人:都义日
-
依托单位:
补肾健脾祛瘀方调控AGE/RAGE信号通路在再生障碍性贫血骨髓间充质干细胞功能受损的作用与机制研究
-
批准号:--
-
项目类别:面上项目
-
资助金额:52万元
-
批准年份:2022
-
负责人:叶宝东
-
依托单位:
LncRNA GAS5在2型糖尿病动脉粥样硬化中对AGE-RAGE 信号通路上相关基因的调控作用及机制研究
-
批准号:
-
项目类别:省市级项目
-
资助金额:10.0万元
-
批准年份:2022
-
负责人:于海兵
-
依托单位:
围绕GLP1-Arginine-AGE/RAGE轴构建探针组学方法探索大柴胡汤异病同治的效应机制
-
批准号:81973577
-
项目类别:面上项目
-
资助金额:55.0万元
-
批准年份:2019
-
负责人:辛贵忠
-
依托单位:
AGE/RAGE通路microRNA编码基因多态性与2型糖尿病并发冠心病的关联研究
-
批准号:81602908
-
项目类别:青年科学基金项目
-
资助金额:18.0万元
-
批准年份:2016
-
负责人:刘括
-
依托单位: