Failure to phosphorylate AKT in podocytes from mice with early diabetic nephropathy promotes cell death.
Kidney Int
; 73(12): 1385-93, 2008 Jun.
Article
em En
| MEDLINE
| ID: mdl-18385666
ABSTRACT
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-alpha 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Nefropatias Diabéticas
/
Podócitos
/
Proteínas Proto-Oncogênicas c-akt
Limite:
Animals
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article