PHOSPHOLIPIDS, DIABETES, AND GLOMERULAR PATHOLOGY

磷脂、糖尿病和肾小球病理学

• 批准号: 3447287
• 负责人: DEAN A TROYER
• 金额: $ 5.27万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3447287
• 关键词: angiotensins; arginine vasopressin; chromatography; deficient growth media; dietary supplements; disease /disorder model; electron microscopy; glomerular filtration; histochemistry /cytochemistry; hormone regulation /control mechanism; hyperglycemia; kidney circulation; lipid metabolism; membrane permeability; nephrosclerosis; neural conduction; nutrition related tag; phosphatidylinositols; radiotracer; renal glomerulus; tissue /cell culture

Glomerular mesangial cells seem to regulate glomerular hemodynamics by their contractile function. Alterations to the contractile properties of these cells in diabetes mellitus could result in glomerulosclerosis by a hemodynamic mechanism. Cultured mesangial cells undergo a calcium-dependent contraction when treated with angiotensin II and vasopressin. Associated with contraction induced by vasopressin, there is an accelerated turnover of phosphotidylinositol. This is often referred to as the "PL effect" and it has been reported to play an important role in hormone-mediated intracellular events that require calcium. Inositol, which is a growth factor for many cell types as well as a necessary substrate for phosphatidylinositol synthesis, is deficient in diabetes mellitus. Thus, under these circumstances mesangial cell growth and function may be seriously compromised. In this application, we propose to study inositide metabolism and function in cultured mesangial cells under baseline and hormone-stimulated conditions (with angiotensin II and arginine vasopressin). These same metabolic studies will be conducted in cultured mesangial cells under conditions of inositol deficiency, and imposed glucose excess. In addition, studies will be initiated to determine if correction of the inositol defect by dietary supplementation or Sorbinil treatment in experimental models of diabetes mellitus will ameliorate the glomerulosclerosis.

肾小球系膜细胞似乎通过以下方式调节肾小球血流动力学 他们的收缩功能。 收缩特性的改变 糖尿病中的这些细胞可能会导致肾小球硬化 血流动力学机制。 培养的系膜细胞经历 当用血管紧张素 II 治疗时，钙依赖性收缩 加压素。 与加压素引起的收缩有关， 磷脂酰肌醇的加速周转。 这一点经常被提及 被称为“PL效应”，据报道它在 激素介导的需要钙的细胞内事件。 肌醇， 它是许多细胞类型的生长因子，也是必需的 磷脂酰肌醇合成的底物，糖尿病患者缺乏 梅利图斯。 因此，在这种情况下，系膜细胞的生长和 功能可能会受到严重损害。 在本申请中，我们建议 研究肌苷在培养系膜细胞中的代谢和功能 基线和激素刺激条件（血管紧张素 II 和 精氨酸加压素）。 这些相同的代谢研究将在 在肌醇缺乏的条件下培养的系膜细胞，以及 施加葡萄糖过量。 此外，还将启动研究 确定是否可以通过膳食补充剂纠正肌醇缺陷 或索比尼尔治疗糖尿病实验模型将 改善肾小球硬化。