PATHOPHYSIOLOGY AND MOLECULAR GENETIC BASIS OF GOUTY DIATHESIS

痛风素质的病理生理学和分子遗传学基础

• 批准号: 7606307
• 负责人: KHASHAYAR SAKHAEE
• 金额: $ 2.13万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7606307
• 关键词: Acid-Base Equilibrium; Ammonium; Buffers; Computer Retrieval of Information on Scientific Projects Database; Defect; Disease susceptibility; Dyslipidemias; Excretory function; Functional disorder; Funding; Goals; Grant; Institution; Insulin; Insulin Resistance; Kidney; Molecular Genetics; Nephrolithiasis; Nonesterified Fatty Acids; Peripheral; Precipitation; Research; Research Personnel; Resources; Secondary to; Source; Syndrome; United States National Institutes of Health; Uric Acid; Urine; base; urinary

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall goal of this project is to elucidate pathophysiologic basis of gouty diathesis and uric acid nephrolithiasis. Gouty diathesis is a descriptive term applied to a syndrome characterized by uric acid nephrolithiasis, varying degrees of renal uric acid retention, and dyslipidemia. Uric acid precipitation in the urine is secondary to acidic urine pH, which renders the uric acid insoluble but the cause of the acidic urine pH is unknown. We have shown that the acidic urine pH is secondary to defects in urinary ammonium excretion' the major urinary buffer. Furthermore, the reduced urinary ammonium can be correlated with the degree of peripheral insulin resistance. The study hypothesis: That a manifestation of insulin resistance in the kidney is impaired ammonium excretion. The reduction of urinary ammonium excretion can be due to decreased insulin action on the kidney per se or secondary to the elevated free fatty acid levels associated with insulin resistance. although the reduced ammonium excretion is insufficient to disturb acid-base balance, it is sufficient to lower urinary pH and cause uric acid precipitation. This "renal insulin resistance" is part of the syndrome of gouty diathesis and contributes directly to uric acid precipitation.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 该项目的总体目的是阐明痛风透明和尿酸肾物石病的病理生理基础。 痛风透明是一种描述性术语，用于尿酸肾石岩症，不同程度的肾尿酸保留和血脂异常的综合征。 尿液中的尿酸沉淀是酸性尿液pH的继发的，这使尿酸不溶性溶解，但酸性尿液pH的原因尚不清楚。 我们已经表明，酸性尿液pH是尿铵排泄缺陷的第二个主要尿缓冲液。 此外，尿铵还原可能与周围胰岛素抵抗的程度相关。 研究假设： 肾脏中胰岛素抵抗的表现是铵排泄受损。 尿铵排泄的减少可能是由于胰岛素对肾脏的作用降低或继发于与胰岛素抵抗相关的自由脂肪酸水平升高所致。 尽管减少的铵排泄不足以干扰酸碱平衡，但足以降低尿液pH值并导致尿酸沉淀。 这种“肾胰岛素抵抗”是痛风素质综合征的一部分，直接有助于尿酸沉淀。