High glucose reduces hepatic glycogenesis by suppression of microRNA‑152

MicroRNAs (miRNAs) are a class of non‑coding 18‑25-nucleotide endogenous RNA molecules. miRNAs act as specific gene silencers to regulate target gene expression at the posttranscriptional level, by base pairing to the 3'‑untranslated region of the target mRNA. miR‑152 is an miRNA that was originally identified in cancer cells, and was shown to be able to modulate the expression of specific oncogenes and tumor suppressor genes, leading to enhanced carcinoma growth. However, little is known regarding the role of miR‑152 in the regulation of hepatic insulin resistance and glucose metabolism. In the present study, it was identified that the activation of AKT and glycogen synthase kinase 3 (GSK‑3), and the expression levels of glycogen, were reduced in mouse NCTC 1469 hepatocytes and mouse primary hepatocytes, following exposure to 25 mM glucose for 48 h. Furthermore, it was demonstrated that high glucose levels suppressed the expression of miR‑152 in hepatocytes. In order to further assess the effects of miR‑152 on the glucose‑induced reduction of glycogen synthesis and activation of AKT and GSK, miR‑152 mimic and inhibitor were transfected into the NCTC 1469 cells, respectively. The transfection of the miR‑152 inhibitor resulted in reduced expression of glycogen, accompanied by impaired phosphorylation of AKT and GSK in the NCTC 1469 cells treated with or without glucose. Conversely, upregulation of miR‑152 by transfection of an miR‑152 mimic reversed the glucose‑induced decrease in glycogen synthesis and reduced AKT and GSK phosphorylation in hepatocytes. This indicated that miR‑152 could modulate the AKT/GSK pathway and glycogen synthesis. In conclusion, to the best of our knowledge, this study was the first to indicate that high glucose impaired the activation of the AKT/GSK pathway and the synthesis of glycogen in mouse hepatocytes, in part through the downregulation of miR‑152.