Diabetic nephropathy. Mechanisms of mesangial matrix expansion

Diabetic nephropathy, a major cause of morbidity and mortality in patients with diabetes mellitus, is characterized by the progressive expansion of mesangial matrix that ultimately occludes glomerular capillaries. Multiple factors in the abnormal metabolic milieu of diabetes contribute to the development of increased amounts of mesangial matrix. Glucose stimulates an increase in synthesis of most collagens and matrix glycoproteins normally expressed within the mesangium. Abnormal glycosylation of matrix proteins interferes with their degradation and turnover. Periods of hyperinsulinemia and alterations in angiotensin II induce changes in the phenotype of mesangial cells and the composition of matrix they secrete. Together, glucose, insulin, and angiotensin II conspire to produce an unrelenting increase in accumulation of mesangial matrix, with altered composition and function.