Mechanism of Astragalus polysaccharides in attenuating insulin resistance in Rats with type 2 diabetes mellitus via the regulation of liver microRNA‑203a‑3p.

Abstract

Insulin resistance (IR) is a common feature of type 2 diabetes mellitus (T2DM). Astragalus polysaccharides (APS) is a natural medicine that is used to treat T2DM. However, the mechanism by which APS regulates micro (mi)RNA in the treatment of IR has not been investigated. The purpose of the present study was to investigate differential miRNA expression between normal, T2DM model and APS treatment rats, as well as changes in miRNA and its downstream gene expression levels after APS treatment in T2DM Goto Kakizaki (GK) rats. Results suggested that miRNA (miR)-203a-3p expression level was significantly decreased in the liver of T2DM GK rats. Furthermore, it was identified that glucose-regulated protein (GRP)78 was the target gene of miR-203a-3p. GRP78 mRNA and protein expression levels of GRP78, CAAT-enhancer-binding protein homologous protein (CHOP), phosphorylated-c-Jun N-terminal kinase (pJNK)1, and caspase-12 were significantly increased in the liver of T2DM GK rats. Furthermore, miR-203a-3p was upregulated following APS treatment, and the protein expression levels of GRP78, CHOP, pJNK1 and caspase-12 were significantly decreased. In addition, miR-203a-3p overexpression in IR cells decreased the protein expression levels of these factors and anti-miR-203a-3p produced the opposite result. These findings provided evidence that miR-203a-3p may have a functional role in endoplasmic reticulum stress (ERS) signaling in the liver of T2DM GK rats. In addition, APS attenuated IR in T2DM, likely through upregulating or maintaining the miR-203a-3p expression levels, decreasing GRP78 mRNA and protein expression levels and regulating the protein expression of the ERS signaling pathway.