Article

Metformin regulates palmitate-induced apoptosis and ER stress response in HepG2 liver cells.

Department of Pharmacology and Institute of Cardiovascular Research, School of Medicine, Chonbuk National University, Chonbuk, Republic of Korea.
Immunopharmacology and Immunotoxicology (impact factor: 1.83). 06/2010; 32(2):251-7. DOI:10.3109/08923970903252220 pp.251-7
Source: PubMed

ABSTRACT The excessive supply of fatty acids to the liver contributes to hepatic insulin resistance and endoplasmic reticulum (ER) stress associated with obesity or type 2 diabetes mellitus. Furthermore, excess and/or prolonged ER stress contributes to hepatic cell death deteriorating nonalcoholic fatty liver disease to steatohepatitis. The aim of this study was to investigate the effects of metformin on palmitate-induced ER stress and hepatic insulin resistance in HepG2 cells. Metformin significantly inhibited palmitate-induced cell death and apoptosis via caspase-3 activation. Metformin also blocked the induction of ER stress proteins (GRP78, Chop, Cleaved ATF-6, p-eIF2 alpha and XBP-1) and regulated serine phosphorylation of IRS-1. Metformin may therefore protect hepatocytes from death induced by saturated fatty acids. These data may also provide a further rationale for exploring the use of metformin in the treatment of non-alcoholic fatty liver disease, revealing its blocking effect for hepatic insulin resistance evoked by saturated fatty acids.

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Keywords

blocking effect
 
caspase-3 activation
 
excessive supply
 
hepatic cell death
 
hepatic insulin resistance
 
hepatic insulin resistance evoked
 
hepatocytes
 
HepG2 cells
 
IRS-1
 
liver contributes
 
metformin
 
non-alcoholic fatty liver disease
 
nonalcoholic fatty liver disease
 
p-eIF2 alpha
 
serine phosphorylation
 
steatohepatitis
 
type 2 diabetes mellitus