Insulin is a potent survival factor in mesangial cells: role of the PI3-kinase/Akt pathway

Kidney International
K HiromuraS J Shankland

Abstract

Elucidating the mechanisms of apoptosis is important for understanding the molecular mechanisms underlying glomerular disease. The phosphatidylinositol 3 kinase (PI3-kinase)/Akt pathway is essential for survival signaling in non-renal cells. However, little is known about the anti-apoptotic effect of insulin and the role of the PI3-kinase/Akt pathway in mesangial cells (MC) apoptosis. Apoptosis was induced in wild type, p27Kip1 (p27) -/- and p21Cip1/Waf1 (p21) -/- mouse MC by survival factor withdrawal, actinomycin D, ultraviolet (UV)-B irradiation and cycloheximide in the presence or absence of insulin (1 micromol/L) or insulin-like growth factor-I (IGF-I; 100 ng/mL). The activation and levels of Akt, extracellular signal regulated kinase (ERK) and specific cell cycle proteins were determined by Western blot analysis. Insulin and IGF-I inhibited wild-type MC apoptosis induced by survival factor withdrawal, actinomycin D, ultraviolet-B irradiation and cycloheximide and in p27 -/- MC when apoptosis was induced by survival factor withdrawal. Akt was activated by insulin and IGF-I during apoptosis. Blocking PI3-kinase with LY294002 reduced Akt activation and abrogated the anti-apoptotic effect of insulin. ERK was activated during ...Continue Reading

References

Apr 1, 1991·International Journal of Radiation Biology·S J Martin, T G Cotter
Sep 29, 1995·The Journal of Biological Chemistry·A S ClarkeA M Mercurio
Feb 1, 1996·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·A K BerfieldC K Abrass
Apr 30, 1998·Current Opinion in Cell Biology·J Downward
May 19, 1998·Nature Medicine·V OphascharoensukS J Shankland
Jun 17, 1998·Proceedings of the National Academy of Sciences of the United States of America·N AhmadH Mukhtar
Jun 19, 1998·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·R Hirschberg, S Adler
Aug 1, 1998·The Journal of Biological Chemistry·M Pap, G M Cooper
Dec 5, 1998·Biochimica Et Biophysica Acta·D R Alessi, C P Downes
Feb 2, 1999·Experimental Cell Research·A L Gartel, A L Tyner
Mar 13, 1999·The Journal of Clinical Investigation·K HiromuraS J Shankland
Sep 15, 1999·Nature·A Khwaja
Nov 2, 1999·Biochemical and Biophysical Research Communications·Y Ishikawa, M Kitamura
Dec 28, 1999·Kidney International·J Savill
Feb 17, 2000·Arteriosclerosis, Thrombosis, and Vascular Biology·C HermannS Dimmeler
Apr 25, 2000·Biochemical and Biophysical Research Communications·M P MoralesS Lavandero
Apr 25, 2000·Journal of Molecular and Cellular Cardiology·A K JonassenD M Yellon
Sep 20, 2000·The Journal of Biological Chemistry·X WangN J Holbrook
Oct 24, 2000·Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society·P NavarroM Lorenzo
Oct 24, 2000·Kidney International·A Ortiz

❮ Previous
Next ❯

Citations

Jul 11, 2006·Journal of Proteome Research·Michelle T BaratiKenneth R McLeish
Nov 1, 2008·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Kumiko KaifuMasakazu Kohno
Jul 15, 2005·Kidney International·Kojiro NagaiHidenori Arai
Mar 9, 2010·PloS One·Peter V HauserStuart J Shankland
Jun 26, 2008·Reproduction : the Official Journal of the Society for the Study of Fertility·Erica LoudenKelle H Moley
Dec 6, 2014·Hematology/oncology Clinics of North America·Junga LeeJeffrey A Meyerhardt
Feb 10, 2006·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Manoranjan SantraMichael Chopp
Jul 22, 2008·Experimental Biology and Medicine·Jana ZdychováRadko Komers
Apr 28, 2004·Archives of Biochemistry and Biophysics·Donghwan ShimHak Yong Kim
Jul 6, 2005·International Journal of Obesity : Journal of the International Association for the Study of Obesity·M P-S LeeG Sweeney
Feb 26, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Min Kyung Cho, Sang Geon Kim
Jul 18, 2019·Aging Cell·Gayoung LeeHunjoo Ha
Dec 11, 2002·American Journal of Physiology. Renal Physiology·Xianghong ZhangYouhua Liu
Nov 1, 2016·Nature Reviews. Nephrology·Ferruh ArtuncHans-Ulrich Häring
Mar 29, 2014·American Journal of Physiology. Renal Physiology·Eva MárquezMaría José Soler

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.