PHOSPHOLIPIDS, DIABETES, AND GLOMERULAR PATHOLOGY

肾小球系膜细胞似乎调节肾小球血流动力学， 收缩功能。 收缩特性的改变 糖尿病患者的这些细胞可能通过一种 血流动力学机制 培养的系膜细胞经历一个 用血管紧张素II治疗时的钙依赖性收缩， 加压素 与加压素诱导的收缩相关， 磷脂酰肌醇的加速周转。 这通常被称为 被称为“PL效应”，据报道，它在 钙离子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， 磷脂酰肌醇合成底物，在糖尿病中缺乏 糖尿病。 因此，在这些情况下，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 体外培养肾小球系膜细胞肌醇代谢及功能的研究 基线和血管紧张素刺激条件（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，和 施加葡萄糖过量。 此外，还将开展研究， 确定是否通过膳食补充剂纠正肌醇缺陷 或糖尿病实验模型中的Sorbinil治疗将 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.