title: Phosphorylation events implicating p38 and PI3K mediate tungstate-effects in MIN6 beta cells.
abstract: Oral administration of sodium tungstate is an effective treatment for diabetes in animal models. Several lines of evidence indicate the pancreatic beta cell as one of the targets of tungstate action. Here, we examined the molecular mechanism by which this compound exerts its effects on the beta cell line MIN6. Tungstate treatment induced phosphorylation and subsequent activation of p38 and PI3K which in turn are implicated in tungstate PDX-1 nuclear localization and activation. Although no effect was observed in glucose-induced insulin secretion we found that tungstate activates basal insulin release, a process driven, at least in part, by activation of p38. These results show a direct involvement of p38 and PI3K phosphorylation in the mechanism of action of tungstate in the beta cell.
authors.affiliation: Endocrinology and Diabetes Unit, Department of Medicine, Hospital Clínic/IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Piquer
authors.forename: Sílvia
authors.initials: S
authors.lastname: Barceló-Batllori
authors.forename: Marta
authors.initials: M
authors.lastname: Julià
authors.forename: Nuria
authors.initials: N
authors.lastname: Marzo
authors.forename: Belen
authors.initials: B
authors.lastname: Nadal
authors.forename: Joan J
authors.initials: JJ
authors.lastname: Guinovart
authors.forename: Ramon
authors.initials: R
authors.lastname: Gomis
mesh_terms: D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D018398:Homeodomain Proteins / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D015534:Trans-Activators / Q000378:metabolism*; D017973:Tungsten Compounds / Q000008:administration & dosage*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; D015534:Trans-Activators; D017973:Tungsten Compounds; C084010:pancreatic and duodenal homeobox 1 protein; D019869:Phosphatidylinositol 3-Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C045951:tungstate