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, Oliver Lenz, Sharon Elliot, Alessia Fornoni

Research output: Contribution to journalArticle

95 Citations (Scopus)

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
Pages (from-to)1385-1393
Number of pages9
JournalKidney International
Volume73
Issue number12
DOIs
StatePublished - Jun 1 2008

Fingerprint

Podocytes
Diabetic Nephropathies
Cell Death
Phosphorylation
Insulin
Proto-Oncogene Proteins c-akt
Albuminuria
Cell Survival
Tumor Necrosis Factor-alpha
Apoptosis
Serum

Keywords

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

ASJC Scopus subject areas

  • Nephrology

Cite this

Failure to phosphorylate AKT in podocytes from mice with early diabetic nephropathy promotes cell death. / Tejada, T.; Catanuto, P.; Ijaz, A.; Santos, J. V.; Xia, X.; Sanchez, P.; Sanabria, N.; Lenz, Oliver; Elliot, Sharon; Fornoni, Alessia.

In: Kidney International, Vol. 73, No. 12, 01.06.2008, p. 1385-1393.

Research output: Contribution to journalArticle

Tejada, T. ; Catanuto, P. ; Ijaz, A. ; Santos, J. V. ; Xia, X. ; Sanchez, P. ; Sanabria, N. ; Lenz, Oliver ; Elliot, Sharon ; Fornoni, Alessia. / Failure to phosphorylate AKT in podocytes from mice with early diabetic nephropathy promotes cell death. In: Kidney International. 2008 ; Vol. 73, No. 12. pp. 1385-1393.
@article{27dfdcfb75a24ffc81925be188def88a,
title = "Failure to phosphorylate AKT in podocytes from mice with early diabetic nephropathy promotes cell death",
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.",
keywords = "AKT, Cell death, Diabetic nephropathy, Insulin signaling, Podocytes",
author = "T. Tejada and P. Catanuto and A. Ijaz and Santos, {J. V.} and X. Xia and P. Sanchez and N. Sanabria and Oliver Lenz and Sharon Elliot and Alessia Fornoni",
year = "2008",
month = "6",
day = "1",
doi = "10.1038/ki.2008.109",
language = "English",
volume = "73",
pages = "1385--1393",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "12",

}

TY - JOUR

T1 - Failure to phosphorylate AKT in podocytes from mice with early diabetic nephropathy promotes cell death

AU - Tejada, T.

AU - Catanuto, P.

AU - Ijaz, A.

AU - Santos, J. V.

AU - Xia, X.

AU - Sanchez, P.

AU - Sanabria, N.

AU - Lenz, Oliver

AU - Elliot, Sharon

AU - Fornoni, Alessia

PY - 2008/6/1

Y1 - 2008/6/1

N2 - 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.

AB - 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.

KW - AKT

KW - Cell death

KW - Diabetic nephropathy

KW - Insulin signaling

KW - Podocytes

UR - http://www.scopus.com/inward/record.url?scp=44449119048&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=44449119048&partnerID=8YFLogxK

U2 - 10.1038/ki.2008.109

DO - 10.1038/ki.2008.109

M3 - Article

C2 - 18385666

AN - SCOPUS:44449119048

VL - 73

SP - 1385

EP - 1393

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 12

ER -