Beneficial effect of berberine on hepatic insulin resistance in diabetic hamsters possibly involves in SREBPs, LXRα and PPARα transcriptional programs.

Abstract

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.

• Authors: Xuhan Liu, Guosheng Li, Hua Zhu, Lan Huang, Yali Liu, Chunmei Ma, Chuan Qin
• Journal: Endocrine journal (Endocr J) Vol. 57 Issue 10 Pg. 881-93 ( 2010) ISSN: 1348-4540 [Electronic] Japan
• PMID: 20724798 (Publication Type: Journal Article)

Chemical References

• Hypoglycemic Agents
• Hypolipidemic Agents
• Liver X Receptors
• Orphan Nuclear Receptors
• PPAR alpha
• RNA, Messenger
• Sterol Regulatory Element Binding Proteins
• Berberine

Topics

• Animals
• Berberine (pharmacology, therapeutic use)
• Cricetinae
• Diabetes Mellitus, Type 2 (drug therapy, metabolism, physiopathology)
• Female
• Gene Expression Profiling
• Gene Expression Regulation (drug effects)
• Hypoglycemic Agents (pharmacology, therapeutic use)
• Hypolipidemic Agents (pharmacology, therapeutic use)
• Insulin Resistance
• Liver (drug effects, metabolism)
• Liver X Receptors
• Male
• Mesocricetus
• Obesity (drug therapy, metabolism, physiopathology)
• Oligonucleotide Array Sequence Analysis
• Orphan Nuclear Receptors (genetics, metabolism)
• PPAR alpha (genetics, metabolism)
• RNA, Messenger (metabolism)
• Random Allocation
• Sterol Regulatory Element Binding Proteins (genetics, metabolism)