Micropuncture and morphometric studied will relate glomerular function and structure in rats with experimental type I diabetes, insulin resistance without hyperglycemia, and type II diabetes.
The first aim i s to relate glomerular function to epithelial cell structure in experimental type I diabetes. Recent morphologic studies suggest that hyperfiltration in patients with early type I diabetes is accompanied by a remarkable increase in the width of epithelial cell foot processes. Proposed studies will test the hypothesis that widening of epithelial cell foot processes accounts for the observation that the glomerular ultrafiltration coefficient (Kf) remains normal while peripheral capillary surface area increases in type I diabetes. These studies will further determine whether the increases in Kf which accompany insulin administration and converting enzyme inhibitor therapy are associated with a reduction in foot process width toward normal.
The second aim i s to identify factors responsible for glomerular injury in the setting of insulin resistance without overt hyperglycemia. Proposed studies will be carried out in rats made insulin resistant by fructose feeding. Like insulin resistant humans, these animals develop both hypertension and hyperlipidemia, and have further been shown to develop accelerated glomerulosclerosis. Proposed studies will establish whether drugs which reduce blood pressure and plasma lipid levels retard the development of glomerular injury in this model.
The third aim i s to identify factors responsible for glomerular injury in type a rat model of type II diabetes in which hyperglycemia is associated with experimental type II diabetes is characterized by glomerular hypertrophy and hyperfiltration. Long-term studies will establish whether drugs which reduce blood pressure and plasma lipid levels also retard the development of glomerular injury in this diseases model. The ultimate goal of these studies is to provide a rational basis for treatment aimed at limiting glomerular injury in diabetes mellitus.
