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

• Published in: Life sciences (1973) Vol. 236; p. 116906
• Main Authors: Takahashi, Nobuhiko, Kimura, Atsushi P., Otsuka, Kai, Ohmura, Kazumasa, Naito, Sumiyoshi, Yoshida, Mika, Ieko, Masahiro
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01-11-2019; Elsevier BV
• Subjects: Cell culture; Colorimetry; Deoxyglucose; Diabetes mellitus; Dreh; Gene expression; Glucose; Glucose transport; Long noncoding RNA; Membrane proteins; Metformin; Muscles; Musculoskeletal system; Myotubes; Proteins; Ribonucleic acid; RNA; Skeletal muscle; Therapeutic applications; Western blotting; Dreh; Metformin; Long noncoding RNA; Glucose transport; Skeletal muscle
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2019.116906

The anti-hyperglycemic action of metformin on skeletal muscles is presently unclear. Long noncoding RNAs (lncRNAs) are implicated in multiple cellular functions. This study aims to explore the role of lncRNAs in the glucometabolic action of metformin on skeletal muscle cells.
Metformin 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.
Metformin 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.
The 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.
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