Animal models of diabetes mellitus allow for the manipulation of the metabolic state and the performance of experiments which may shed light on the pathogenesis of diabetic nephropathy. Rats with long standing chemically induced diabetes develop glomerular mesangial thickening and immunoglobulin and complement deposition. These glomerular changes are reversible on the transplantation of a kidney from a diabetic rat into a normal host and on cure of the diabetic state by pancreatic islet transplantation. Conversely, diabetic renal changes develop in normal kidneys transplanted into diabetic rats (within 2 to 4 mth) and humans (within 2 yr). These studies suggest that nephropathy results from the diabetic state. The mesangium is thickened in diabetic rats, mice, and humans. In rats, mesangial function in the processing of macromolecules localized therein is disturbed in areas of mesangial pathology. The finding that glomerulopathy is accelerated in uninephrectomized diabetic rats and is retarded in rat kidneys 'protected' by narrowing of the renal artery suggests that alterations in glomerular blood flow are related to the pathogenesis of diabetic glomerular damage. Marked hyperglycemia in animals and man leads to 'glycogen nephrosis', which affects the distal tubule at the level of the macula densa of the juxtaglomerular apparatus (JGA). This could lead to disturbance of JGA blood pressure regulation. Disturbed mesangial function may result from failure of macula densa cells to process macromolecules that have reached that site from the mesangium.
|Original language||English (US)|
|Number of pages||8|
|State||Published - Dec 1 1976|