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

Abstract

AIM:To i n v e s t i g a t e t h e e f f e c t s a n d m o l e c u l a r 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 m m o l / L ) t o t h e c u l t u re m e d i u m . B e r b e r in e treatment was performed at the same time. Glucose uptake rate was determined by the 2-deoxy-[3 H]-Dglucose method. The levels of IkB kinase beta (IKKβ) Ser 181 phosphorylation, insulin receptor substrate-1(IRS-1) Ser 307 phosphorylation, expression of IKKβ, IRS-1, nuclear transcription factor kappaB p65 (NF-κB p65), phosphatidylinositol-3-kinase p85 (PI-3K p85) and glucose transporter 4 (GLUT4) proteins were detected by Western blotting. The distribution of NF-κB 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 e x p re s s i o n o f I R S -1 a n d P I-3 K p 8 5 p ro t e i n wa s reduced, while the levels of IKKβ Ser 181 and IRS-1 Ser 307 phosphorylation, and nuclear translocation of NF-κB p65 protein were increased. However, the above indexes, which indicated the existence of insulin resistance, were reversed by berberine although the expression of GLUT4, IKKβ and total NF-κB 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 IKKβ.

Kaempferol alleviates insulin resistance via hepatic IKK/NF-κB signal in type 2 diabetic rats

“…The antiinflammation activity of KPF has been reported in vitro and in vivo by other studies [14,36], and our work also confirmed its antiinflammatory effect in T2DM. High-dose of salicylate is a potent inhibitor of inflammation, which prevents insulin resistance by inhibiting IKKβ activation, and our results were in accordance with those reports by Sun et al [18,37].…”

Oxidized LDL impair adipocyte response to insulin by activating serine/threonine kinases

“…by the activation of the two serine/threonine kinases, which have been previously demonstrated to be activated by the proinflammatory conditions associated with insulin resistance (26,83,84). The involvement of IKKb and JNK in our experimental model was in agreement with several published papers, which have suggested serine kinases activation as an intervening mechanism in inducing insulin resistance (25,(30)(31)(32)(33)(34)(85)(86)(87).…”

Antidiabetic Properties of Berberine: From Cellular Pharmacology to Clinical Effects

“…29,30 In the 3T3-L1 adipocytes model of insulin resistance, berberine reverses 1κB kinase beta Ser(181) and insulin receptor substrate-1 (IRS-1) Ser(307) phosphorylation, improves insulin-stimulated glucose transport, and reverses free fatty acid-induced insulin resistance (palmitic acid in this study). 31 Berberine seems to improve insulin resistance by upregulating IRS-2 mRNA expression in nonalcoholic fatty liver disease in the rat liver. 32 However, in another study, which was conducted on 3T3-L1 adipocytes, berberine did not augment IRS-1 or insulin receptor tyrosine phosphorylation.…”