The "lipotoxicity" hypothesis holds that fat-induced hepatic
insulin resistance (FIHIR) may play a major role in the pathogenesis of
type 2 diabetes.
Berberine has been reported to have
antidiabetic properties. However, the molecular mechanisms for this action are not fully clarified. Therefore, we will investigate the gene expression alterations involved in the
therapeutic effect of
berberine on FIHIR in diabetic hamsters and possible mechanisms. In this study, type 2 diabetic hamsters were induced by high-fat diet with
streptozotocin injection. After 9 weeks of
berberine-treatment, the gene expression alterations involved in the therapeutic molecular mechanisms of
berberine on FIHIR will be studied by microarray technology and real time RT-PCR. Our study demonstrates
berberine significantly improved fat-induced
insulin resistance and diabetic phenotype in type 2 diabetic hamsters. The alterations of certain metabolism related genes and their main regulators:
Liver X receptor (LXR) α,
Peroxisome proliferator-activated receptor (
PPAR) α and
Sterol regulatory element-binding protein (SREBPs) are observed in the liver of treated and untreated diabetic hamsters. Compared with diabetic hamsters, the increased
mRNA levels of LXRα and PPARα and the decreased
mRNA levels of SREBPs are observed in
berberine-treated diabetic hamster. The statistical significance of the expression of hepatic LXRα, SREBPs and PPARα and their certain target genes is found between treated and untreated diabetic hamsters. These results suggest that altered hepatic SREBPs, LXRα and PPARα transcriptional programs possibly involve in the therapeutic mechanisms of
berberine on FIHIR in type 2 diabetic hamsters.