Glomerular changes in diabetes mellitus.
Ultrastructural, immunohistochemical and biochemical studies have improved our knowledge on the events occurring during the development of diabetic late complications. Immunohistochemical investigations of diabetic kidneys, using antibodies against various components of the extracellular matrix, showed increased collagen type IV (alpha 1,alpha 2-chain) deposition in the mesangial matrix, and a decrease of heparan sulphate proteoglycan in the mesangial matrix and glomerular basement membrane. Changes in matrix components seem to be the underlying cause of the alterations in renal function, as reflected by albuminuria and proteinuria. The occurrence of collagen type III in late diffuse glomerulosclerosis has been interpreted as an irreversible change in glomerular structure. The extent of alteration of the extracellular matrix correlates to a certain extent with the severity of nephropathy of the individual subject. The studies performed to date support the hypothesis that hyperglycaemia, whatever its origin, is the primary cause of diabetic late complications, although the pathobiochemical mechanisms are not yet fully understood. Increased intra- and extracellular levels of glucose and its derivatives are thought to contribute to diabetic tissue dysfunction. Three pathobiochemical theories are favoured in the current discussion: i) the polyol pathway ii) non-enzymatic glycation of proteins iii) direct influence of hyperglycaemia on the synthesis of matrix components. The evidence for the participation of the polyol pathway in the pathogenesis of diabetic nephropathy comes mainly from animal data using aldose reductase inhibitors, but only limited data are available for humans, so that the significance of this pathomechanism cannot yet be determined.(ABSTRACT TRUNCATED AT 250 WORDS)
Schleicher
E D
ED
Institut für Diabetesforschung, München.
Olgemöller
B
B
D000818:Animals; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000378:metabolism / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure