PHOSPHOLIPIDS, DIABETES, AND GLOMERULAR PATHOLOGY

肾小球系膜细胞似乎通过以下途径调节肾小球血流动力学 它们的收缩功能。对收缩性能的改变 糖尿病患者的这些细胞可通过一种 血流动力学机制。培养的肾小球系膜细胞经历 血管紧张素II和血管紧张素转换酶治疗时的钙依赖性收缩 加压素。与加压素引起的收缩有关，有 磷脂酰肌醇的加速周转。这通常指的是 作为“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，也是必要的 合成磷脂酰肌醇的底物，在糖尿病中缺乏 糖尿病。因此，在这种情况下，系膜细胞生长和 功能可能会严重受损。在本申请中，我们建议 肌醇磷脂在体外培养的肾小球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)。这些相同的新陈代谢研究将在 在肌醇缺乏条件下培养的系膜细胞，以及 强加的葡萄糖过量。此外，还将启动研究，以 确定是否通过饮食补充来纠正肌醇缺陷 或索比尼治疗实验性糖尿病模型将 改善肾小球硬化。

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.