title: Riluzole increases the rate of glucose transport in L6 myotubes and NSC-34 motor neuron-like cells via AMPK pathway activation.
abstract: Riluzole is the only approved ALS drug. Riluzole influences several cellular pathways, but its exact mechanism of action remains unclear. Our goal was to study the drug's influence on the glucose transport rate in two ALS relevant cell types, neurons and myotubes. Stably transfected wild-type or mutant G93A human SOD1 NSC-34 motor neuron-like cells and rat L6 myotubes were exposed to riluzole. The rate of glucose uptake, translocation of glucose transporters to the cell's plasma membrane and the main glucose transport regulatory proteins' phosphorylation levels were measured. We found that riluzole increases the glucose transport rate and up-regulates the translocation of glucose transporters to plasma membrane in both types of cells. Riluzole leads to AMPK phosphorylation and to the phosphorylation of its downstream target, AS-160. In conclusion, increasing the glucose transport rate in ALS affected cells might be one of the mechanisms of riluzole's therapeutic effect. These findings can be used to rationally design and synthesize novel anti-ALS drugs that modulate glucose transport in neurons and skeletal muscles.
authors.affiliation: Division of Medicinal Chemistry, Department of Chemistry, Faculty of Exact Sciences, Bar Ilan University, Ramat Gan, Israel.
authors.forename: Bareket
authors.initials: B
authors.lastname: Daniel
authors.forename: Omer
authors.initials: O
authors.lastname: Green
authors.forename: Olga
authors.initials: O
authors.lastname: Viskind
authors.forename: Arie
authors.initials: A
authors.lastname: Gruzman
mesh_terms: D000263:Adenylate Kinase / Q000502:physiology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism*; D051246:Glucose Transport Proteins, Facilitative / Q000187:drug effects* / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000187:drug effects / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009046:Motor Neurons / Q000187:drug effects* / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D019782:Riluzole / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000235:genetics
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; C495679:Slc2a1 protein, rat; C495694:Slc2a4 protein, rat; D019782:Riluzole; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; D000263:Adenylate Kinase; D005947:Glucose