Failure to phosphorylate AKT in podocytes from mice with early diabetic nephropathy promotes cell death

T. Tejada, P. Catanuto, A. Ijaz, J. V. Santos, X. Xia, P. Sanchez, N. Sanabria, O. Lenz, S. J. Elliot, A. Fornoni

Research output: Contribution to journalArticle

103 Scopus citations

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-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.

Original languageEnglish (US)
Pages (from-to)1385-1393
Number of pages9
JournalKidney international
Volume73
Issue number12
DOIs
StatePublished - Jun 2008

Keywords

  • AKT
  • Cell death
  • Diabetic nephropathy
  • Insulin signaling
  • Podocytes

ASJC Scopus subject areas

  • Nephrology

Fingerprint Dive into the research topics of 'Failure to phosphorylate AKT in podocytes from mice with early diabetic nephropathy promotes cell death'. Together they form a unique fingerprint.

  • Cite this