Long-term beneficial effects of vanadate, tungstate, and molybdate on insulin secretion and function of cultured beta cells.
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.
Liu
Hui-Kang
HK
School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland, UK.
Green
Brian D
BD
McClenaghan
Neville H
NH
McCluskey
Jane T
JT
Flatt
Peter R
PR
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
D007004:Hypoglycemic Agents; D007328:Insulin; D014131:Trace Elements; D017973:Tungsten Compounds; C044659:molybdate; D014638:Vanadates; D008982:Molybdenum; C045951:tungstate