Abstract
The glomerular mesangium is the site of prominent structural lesions in diabetic nephropathy, including excess deposition of extracellular matrix in a focal, nodular pattern. Increased single-nephron blood flow and filtration are early signs of glomerular involvement in diabetes, and may initiate or contribute to mesangial damage. Vasodilatation results from arteriolar insensitivity to vasoconstrictors. In turn, this may reflect primary metabolic defects of glomerular smooth muscle, including the afferent arteriole and mesangial cells themselves. Parallel alterations in the glomerular basement membrane and related structures, such as mesangial matrix, are likely to result from glycosylation of intrinsic proteins, or accumulation of advanced glycosylation end-products. Structural and haemodynamic changes account for (micro)-albuminuria, with additional possible overloading of the measangium. Mesangial proliferative changes eventually ensue, with excess matrix deposition and progressive fibrosis. Recent evidence that long-standing hyperglycaemia modifies mesangial metabolism, sensitivity to vasoconstrictors and matrix biosynthesis in vitro is reviewed here, in the light of its potential implications for experimental and human diabetic nephropathy.
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Mené, P., Cinotti, G.A. & Pugliese, F. Mesangial cells in diabetes. Acta Diabetol 29, 227–230 (1992). https://doi.org/10.1007/BF00573493
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DOI: https://doi.org/10.1007/BF00573493