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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. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are small non-coding RNAs that are important in the pathogenesis of multiple diseases and, therefore, may represent a novel class of targets for therapeutic intervention. However, like the majority of oligonucleotide-based strategies, there are obstacles to their clinical application, including poor cellular uptake due to the low permeability of the cell membrane to negatively charged molecules. MPG is a 27-residue peptide vector which contains a hydrophobic domain derived from the fusion sequence of HIV-1 gp41 and a hydrophilic domain derived from the nuclear localization sequence of SV40 T-antigen. MPG is one of the most promising tools for the non-invasive cellular import of oligonucleotides and analogs. In the present study, a non-covalent peptide-based strategy was used for the efficient delivery of the miRNA-122 (miR-122) mimic and inhibitor into mouse liver cell lines, mouse primary hepatocytes and C. elegans, without any associated cytotoxicity. Moreover, high-performance liquid chromatography analysis determined that MPG and MPG▵ NLS delivered the miR-122 mimic and inhibitor into mouse liver cells and effectively regulated cholesterol levels. The results demonstrated that MPG family members may be used for the efficient delivery of miR-122 to regulate cholesterol metabolism, and that this cell-penetrating peptide-based technology may be beneficial for further biological applications of RNA therapeutics in vivo. [ABSTRACT FROM AUTHOR]