Loss of podocytes by apoptosis characterizes the early stages of diabetic nephropathy. To examine its mechanism we studied glomeruli and podocytes isolated from db/db mice with early diabetic nephropathy and albuminuria. Phosphorylation of AKT (protein kinase B, a key survival protein) was found to be lower in the glomeruli of 12 week old db/db compared to db/+ mice. In vitro, insulin phosphorylated AKT solely in podocytes from db/+ mice. Serum deprivation and exposure to tumor necrosis factor-α significantly compromised cell viability in podocytes from db/db but not from db/+ mice, and this was associated with a significant decrease in AKT phosphorylation. Inhibition of AKT was necessary to achieve the same degree of cell death in db/+ podocytes. Our study shows that podocyte inability to respond to insulin and susceptibility to cell death may partially account for the decreased podocyte number seen in early diabetic nephropathy. © 2008 International Society of Nephrology.
CITATION STYLE
Tejada, T., Catanuto, P., Ijaz, A., Santos, J. V., Xia, X., Sanchez, P., … Fornoni, A. (2008). Failure to phosphorylate AKT in podocytes from mice with early diabetic nephropathy promotes cell death. Kidney International, 73(12), 1385–1393. https://doi.org/10.1038/ki.2008.109
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