Bearing in mind the manner in which microangiopathy presents clinically, retinal and renal microvasculature form the principal tissues of study in this research project, although the blood vessels of other regions were also examined routinely. These investigations included metabolic, biochemical, histopathological and electronmicroscopic studies. Diabetes was induced in young Sprague-Dawley male rats by pancreatectomy or by alloxan injections. Some of these diabetic animals were fed an atherogenic diet containing, among thirty-two other adjuvants, 5% cholesterol and 40% fat. Other animals were injected with the lathyrogen , '-imino-dipropionitrile (IDPN). Diabetes per se failed to produce detectable microangiopathy for the period of observation (up to seven months) but appeared to increase the frequency and the severity of atheroma in animals fed the atherogenic diet. With this diet diabetic retinal "cotton-wool" lesions and arteriolarsclerosis were inducible, but retinal aneurysms did not develop. Renal vascular lesions were more prominent and more severe in such animals. These nephropathic changes occurred in both large and small blood vessels as wellas in other non-vascular tissues of the kidney, IDPN-treated diabetic rats showed a more successful and rapid onset of the vascular lesions, including retinal aneurysms, than did non-diabetic rats similarly treated, the effects being even more explosive when the former were kept on the atherogenic diet. Electronmicroscopic studies on the microvasculature of retinae from IHPN-treated diabetic rats revealed abiotrophic changes in the endothelium and increase in width of the basement membrane. Changes in the glomerulus included diffuse proliferation of the endothelium with increased vacuolation, macrovesicle formation and thickening of the capillary basement membrane. The levels of skeletal muscle glycogen remained almost normal in the two forms of diabetic animals. Liver glycogen content was lowered in alloxan-diabetic rats but was almost unchanged in pancreatectomised rats. Both diabetes and the cholesterol diet greatly reduced the phosphorylating activity of glucokinase (EC 220.127.116.11) in the liver. A possible mode of action of IDPN in the acceleration of the development of retinal and renal microangiopathy in the diabetic rat is proposed.
|Date of Award||1969|