Emodin improves glucose metabolism by targeting microRNA-20b in insulin-resistant skeletal muscle

Abstract

Background: Emerging evidence has indicated the therapeutic potential of emodin with its multiple pharmacological effects.

Purpose: To evaluate role of emodin in regulating insulin resistance (IR) and to elucidate the underlying molecular mechanisms.

Study design/methods: Fasting blood glucose (FBG) and lipid levels were measured before and after intragastric administration of emodin in type 2 diabetes mellitus (T2DM) rats. Glucose consumption was determined in L6 cells to investigate the effect of emodin on glucose metabolism. Expression of miR-20b and SMAD7 was quantified by real-time PCR for mRNAs or western blot analysis for proteins.

Results: Emodin ameliorated hyperglycemia and dyslipidemia in T2DM rats, and glucose metabolism in a concentration- and time-dependent manner. MiR-20b was markedly upregulated in the setting of IR and overexpression of miR-20b disrupted glucose metabolism by repressing SMAD7 in L6 cells. Knockdown of this miRNA produced the opposite effects. Emodin abolished the abnormal upregulation of miR-20b and indirectly upregulated SMAD7.

Conclusion: Emodin improves glucose metabolism to produce anti-IR effects, and downregulation of miR-20b thereby upregulation of SMAD7 is an underlying mechanism for the beneficial effects of emodin.

Keywords: Emodin; Insulin resistance; SMAD7; Skeletal muscle; miR-20b.