Dreh, a long noncoding RNA repressed by metformin, regulates glucose transport in C2C12 skeletal muscle cells

This study aims to explore the role of lncRNAs in the glucometabolic action of metformin on skeletal muscle cells.Main methodsMetformin accumulation was assessed using [14C]-metformin. A lncRNA array was used to investigate metformin-regulated lncRNAs in C2C12 skeletal muscle cells. Knockdown studies were applied to evaluate the function of lncRNA Dreh. A colorimetric assay was used for the measurement of medium glucose concentration; glucose transport was assessed using [3H]-2-deoxyglucose; real-time PCR was used for RNA expression analysis, and western blotting was used to assess protein expression in myotubes. A Dreh overexpression plasmid was transfected into the cells.Key findingsMetformin accumulated in C2C12 myotubes. Metformin reduced medium glucose concentration and repressed lncRNA Dreh expression in the myotubes. Knockdown of Dreh in the myotubes resulted in reduced glucose concentration in the culture medium, increased glucose transport, and increased levels of GLUT4 protein in the plasma membrane. Overexpression of Dreh attenuated the glucose-lowering effect of metformin in myotubes.SignificanceThe glucoregulatory actions of metformin are mediated in part by a lncRNA, Dreh, in the skeletal muscle cells. Dreh is a novel regulator for glucose transport and could be a therapeutic target for diabetes.Graphical abstract

Source: Life Sciences - October 13, 2019 Category: Biology Source Type: research