Studies in the diabetic mutant mouse. VI. Evolution of glomerular lesions and associated proteinuria

Light and electron microscopic studies were performed on renal glomeruli of diabetic mutant and age-matched normal mice and correlated with alterations in urinary excretion. The glomeruli of young (prediabetic) mutants and their normal littermates were normal and identical. With increasing age, the glomeruli of normal control mice were characterized by mesangial prominence and increased thickness and nodular densities of the peripheral basal lamina. These alterations were also observed in the diabetic mutant mice but more frequently and to a greatly exaggerated degree. The diabetic mutants were polyuric and excreted a quantity of protein identified by agarose and inmunoelectrophoresis as a serum protein. The excretion of this protein preceded the recognition of the morphologic alterations and did not increase in magnitude with the progression of glomerular changes. This report challenges the theoretic concept of genetically controlled diabetic glomerular lesions and discusses possible relationships between the glomerular alterations, the presence of proteinuria and the presence of hyperglycemia.