title: Long-term beneficial effects of vanadate, tungstate, and molybdate on insulin secretion and function of cultured beta cells.
abstract: The ultratrace elements vanadate, tungstate, and molybdate exhibit significant antihyperglycemic effects in both type 1 and 2 diabetic animals, but possible effects on the function of pancreatic beta cells are understudied. In the present study, clonal BRIN BD11 cells were cultured for 3 days with each ultratrace element to establish doses lacking detrimental effects on viable beta cell mass. Vanadate treatment (4 micromol/L) had no effect on cellular insulin content but improved glucose-induced insulin secretory responsiveness. However, insulin secretion mediated by PKA and PKC activation was desensitized in vanadate-treated cells. Culture with tungstate (300 micromol/L) and molybdate (1 mmol/L) increased cellular insulin content and enhanced basal insulin release and the responsiveness to glucose and a wide range of other secretagogues. These observations suggest significant effects of ultratrace elements on pancreatic beta cells that may contribute to their antihyperglycemic action.
authors.affiliation: School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland, UK.
authors.forename: Hui-Kang
authors.initials: HK
authors.lastname: Liu
authors.forename: Brian D
authors.initials: BD
authors.lastname: Green
authors.forename: Neville H
authors.initials: NH
authors.lastname: McClenaghan
authors.forename: Jane T
authors.initials: JT
authors.lastname: McCluskey
authors.forename: Peter R
authors.initials: PR
authors.lastname: Flatt
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005089:Exocytosis; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008982:Molybdenum / Q000494:pharmacology; D051381:Rats; D014131:Trace Elements / Q000494:pharmacology*; D017973:Tungsten Compounds / Q000494:pharmacology; D014638:Vanadates / Q000494:pharmacology
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D014131:Trace Elements; D017973:Tungsten Compounds; C044659:molybdate; D014638:Vanadates; D008982:Molybdenum; C045951:tungstate