Format

Send to

Choose Destination
Dis Model Mech. 2012 Mar;5(2):259-69. doi: 10.1242/dmm.008110. Epub 2011 Nov 22.

Metformin differentially activates ER stress signaling pathways without inducing apoptosis.

Author information

1
Department of Pediatric Cardiology and Pediatric Intensive Care Medicine, University of Göttingen, Göttingen, Germany. thomas.quentin@med.uni-goettingen.de

Abstract

Endoplasmic reticulum stress signaling (ERSS) plays an important role in the pathogenesis of diabetes and heart disease. The latter is a common comorbidity of diabetes and worsens patient outcome. Results from clinical studies suggest beneficial effects of metformin - a widely used oral drug for the treatment of type 2 diabetes - on the heart of diabetic patients with heart failure. We therefore analyzed the effect of metformin on ERSS in primary rat cardiomyocytes. We found that metformin activates the PERK-ATF4 but not the ATF6 or IRE1-XBP1 branch in ERSS and leads to a strong upregulation of CHOP mRNA and protein. Surprisingly, long-term induction of CHOP by metformin is not accompanied by apoptosis even though CHOP is regarded to be a mediator of ER-stress-induced apoptosis. In conclusion, metformin induces distinct ER stress pathways in cardiomyocytes and our results indicate that CHOP is not necessarily a mediator of apoptosis. Metformin might exert its cardioprotective effect through selective activation of ERSS pathways in the cardiomyocyte.

PMID:
22107872
PMCID:
PMC3291647
DOI:
10.1242/dmm.008110
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center