Berberine Ameliorates Hepatic Insulin Resistance by Regulating microRNA-146b/SIRT1 Pathway

Hepatic insulin resistance is a major initiating factor for type 2 diabetes mellitus. In previous study, Gegen Qinlian Decoction containing berberine could enhance hepatic insulin sensitivity by SIRT1-dependent deacetylation of FOXO1. However, it is not clear whether berberine also can improve hepatic insulin sensitivity by SIRT1/FOXO1 pathway. This study aimed to evaluate the efficacy of berberine for improving hepatic insulin resistance and the possible molecular mechanisms involved.

In vitro, HepG2 cells were induced with palmitic acid, and glycogen synthesis was examined. In vivo, a high-fat diet (HFD)-fed mouse model was established, and metabolic parameters were assessed. The expressions of miR-146b and sirtuin 1 (SIRT1) in liver were also examined. The relationship between miR-146b and SIRT1 was examined by the dual-luciferase reporter gene assay.

Serum biochemical parameters, such as glucose and HOMA-IR index, were increased in HFD mice; miR-146b and SIRT1 were abnormally expressed in HFD mice and palmitic acid-treated HepG2 cells. Interestingly, berberine reduced body weight and caused a significant improvement in glucose tolerance and HOMA-IR index without altering food intake in mice. Overexpression of miR-146b abolished the protective effect of berberine on palmitic acid-induced impaired glycogen synthesis in HepG2 cells. Luciferase assay showed that miR-146b directly targeted SIRT1.

The present findings suggest that berberine could attenuate hepatic insulin resistance through the miR-146b/SIRT1 pathway, which may represent a potential therapeutic target for the prevention and treatment of metabolic diseases, particularly diabetes.