title: Sodium tungstate activates glycogen synthesis through a non-canonical mechanism involving G-proteins.
abstract: Tungstate treatment ameliorates experimental diabetes by increasing liver glycogen deposition through an as yet unidentified mechanism. The signalling mechanism of tungstate was studied in CHOIR cells and primary cultured hepatocytes. This compound exerted its pro-glycogenic effects through a new G-protein-dependent and Tyr-Kinase Receptor-independent mechanism. Chemical or genetic disruption of G-protein signalling prevented the activation of the Ras/ERK cascade and the downstream induction of glycogen synthesis caused by tungstate. Thus, these findings unveil a novel non-canonical signalling pathway that leads to the activation of glycogen synthesis and that could be exploited as an approach to treat diabetes.
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona) and Department of Biochemistry and Molecular Biology, University of Barcelona, and CIBER de Diabetes y Enfermedades Metabólicas (CIBERDEM), Baldiri Reixac 10-12, E-08028 Barcelona, Spain.
authors.forename: Delia
authors.initials: D
authors.lastname: Zafra
authors.forename: Laura
authors.initials: L
authors.lastname: Nocito
authors.forename: Jorge
authors.initials: J
authors.lastname: Domínguez
authors.forename: Joan J
authors.initials: JJ
authors.lastname: Guinovart
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D017973:Tungsten Compounds / Q000494:pharmacology*; D018631:ras Proteins / Q000378:metabolism
chemical_list: D007004:Hypoglycemic Agents; D017973:Tungsten Compounds; C025399:sodium tungstate(VI); D006003:Glycogen; D011972:Receptor, Insulin; D048049:Extracellular Signal-Regulated MAP Kinases; D020962:Heterotrimeric GTP-Binding Proteins; D018631:ras Proteins