STUDY OF GLOMERULAR HYPERFILTRATION IN DIABETES

糖尿病肾病是终末期肾病的主要原因 在人类身上。 在胰岛素依赖型糖尿病的早期 肾小球滤过率可能增加超过 正常 这种肾小球超滤（GH）至少部分是， 导致糖尿病肾病的发生。 本提案的目的是确定 负责这种状态的生长激素使用糖尿病狗作为 实验模型 在有意识的、受过训练的狗的体内研究中，我们将确定 高血糖、胰岛素缺乏、胰腺炎 胰高血糖素，心房利钠肽，血管舒张素， 去甲肾上腺素和血管紧张素11在生长激素中起作用。 作为任何影响 这些因素对生长激素可能是表达在个人 肾小球单位，我们将确定这些因素的影响， 离体肾传入和传出小动脉功能 以及体外研究的完整肾小球单位 确定导致GH的因素可能会 导致进一步的研究，这将阐明细胞 （一）表达这些因素的机制。 此夕h 这些研究的结果应导致发展 旨在预防或改善糖尿病的治疗方案 肾病

Diabetic nephropathy is a major cause of end-stage renal disease in humans. Early in the course of insulin-dependent diabetes mellitus, the glomerular filtration rate may be increased above normal. This glomerular hyperfiltration (GH) is, at least in part, responsible for the development of diabetic nephropathy. The purpose of this proposal is to identify the factor(s) responsible for this state of GH using the diabetic dog as the experimental model. In in-vivo studies in the conscious, trained dog, we will identify the role which hyperglycemia, insulin deficiency, pancreatic glucagon, atrial natriuretic peptide, vasodilatory prostaglandins, norepinephrine and angiotensin 11 play in the GH. As any effect of these factors on GH is likely expressed in the individual glomerular units, we will identify the effect of these factors on the function of isolated renal afferent and efferent arterioles as well as intact glomerular units studied in-vitro Identification of the factor(s) responsible for GH will potentially lead to further studies which will elucidate the cellular mechanism(s) by which the factors are expressed. Further, the results of these studies should lead to the development of therapeutic regimens aimed at preventing or ameliorating diabetic nephropathy.