Berberine reverses free-fatty-acid-induced insulin resistance in 3T3-L1 adipocytes through targeting IKKbeta.

Abstract

AIM:

To investigate the effects and molecular mechanisms of berberine on improving insulin resistance induced by free fatty acids (FFAs) in 3T3-L1 adipocytes.

METHODS:

The model of insulin resistance in 3T3-L1 adipocytes was established by adding palmic acid (0.5 mmol/L) to the culture medium. Berberine treatment was performed at the same time. Glucose uptake rate was determined by the 2-deoxy-[(3)H]-D-glucose method. The levels of IkB kinase beta (IKKbeta) Ser(181) phosphorylation, insulin receptor substrate-1(IRS-1) Ser(307) phosphorylation, expression of IKKbeta, IRS-1, nuclear transcription factor kappaB p65 (NF-kappaB p65), phosphatidylinositol-3-kinase p85 (PI-3K p85) and glucose transporter 4 (GLUT4) proteins were detected by Western blotting. The distribution of NF-kappaB p65 proteins inside the adipocytes was observed through confocal laser scanning microscopy (CLSM).

RESULTS:

After the intervention of palmic acid for 24 h, the insulin-stimulated glucose transport in 3T3-L1 adipocytes was inhibited by 67%. Meanwhile, the expression of IRS-1 and PI-3K p85 protein was reduced, while the levels of IKKbeta Ser(181) and IRS-1 Ser(307) phosphorylation, and nuclear translocation of NF-kappaB p65 protein were increased. However, the above indexes, which indicated the existence of insulin resistance, were reversed by berberine although the expression of GLUT4, IKKbeta and total NF-kappaB p65 protein were not changed during this study.

CONCLUSION:

Insulin resistance induced by FFAs in 3T3-L1 adipocytes can be improved by berberine. Berberine reversed free-fatty-acid-induced insulin resistance in 3T3-L1 adipocytes through targeting IKKbeta.

• Authors: Ping Yi, Fu-Er Lu, Li-Jun Xu, Guang Chen, Hui Dong, Kai-Fu Wang
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 14 Issue 6 Pg. 876-83 (Feb 14 2008) ISSN: 1007-9327 [Print] United States
• PMID: 18240344 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• Fatty Acids, Nonesterified
• Insulin
• Insulin Receptor Substrate Proteins
• Irs1 protein, mouse
• Transcription Factor RelA
• Berberine
• Serine
• Phosphatidylinositol 3-Kinases
• I-kappa B Kinase
• Ikbkb protein, mouse
• Glucose

Topics

• 3T3-L1 Cells
• Active Transport, Cell Nucleus (physiology)
• Adaptor Proteins, Signal Transducing (metabolism)
• Adipocytes (cytology, metabolism)
• Animals
• Berberine (metabolism)
• Fatty Acids, Nonesterified (metabolism)
• Glucose (metabolism)
• I-kappa B Kinase (metabolism)
• Insulin (metabolism)
• Insulin Receptor Substrate Proteins
• Insulin Resistance (physiology)
• Mice
• Phosphatidylinositol 3-Kinases (metabolism)
• Serine (metabolism)
• Transcription Factor RelA (metabolism)