Vanadate stimulation of insulin release in normal mouse islets.
The effects of vanadate (Na3VO4) on pancreatic B-cell function were studied in normal mouse islets. Vanadate did not affect basal insulin release but potentiated the effect of 7-30 mM glucose at concentrations of 0.1-1 mM. This effect was progressive and slowly reversible. It was abolished by omission of extracellular Ca2+ but unaffected by blockers of adrenergic or muscarinic receptors. Comparison of the changes in membrane potential, 86Rb efflux and 45Ca efflux that vanadate and ouabain produced in B-cells made it possible to exclude the hypothesis that vanadate increases insulin release by blocking the sodium pump. Vanadate was also without effect on cAMP levels. On the other hand, it markedly changed the characteristics of the Ca(2+)-dependent electrical activity and of the oscillations of cytoplasmic Ca2+ recorded in B-cells stimulated by 15 mM glucose. In the steady state, Ca2+ influx was increased by vanadate, and this resulted in a rise in cytoplasmic Ca2+. The exact mechanisms underlying these changes could not be established but a blockade of K channels was excluded. In the presence of LiCl, vanadate markedly increased inositol phosphate levels in islet cells. This effect was attenuated but not suppressed by omission of Ca2+. A small increase in inositol bisphosphate was still produced by vanadate in the absence of LiCl. These results suggest that vanadate both stimulates phosphoinositide breakdown and inhibits inositol phosphate degradation. In conclusion, vanadate does not induce insulin release, but markedly potentiates the stimulation by glucose. This property is not due to an inhibition of the sodium pump or to a rise in cAMP concentration. It results from a complex interplay between changes in B-cell membrane potential, phosphoinositide metabolism and Ca2+ handling.
Zhang
A Q
AQ
Unité de Diabétologie et Nutrition, University of Louvain Faculty of Medicine, Brussels, Belgium.
Gao
Z Y
ZY
Gilon
P
P
Nenquin
M
M
Drews
G
G
Henquin
J C
JC
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D010042:Ouabain / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D012413:Rubidium / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology*
D007295:Inositol Phosphates; D007328:Insulin; D014638:Vanadates; D010042:Ouabain; D001285:Atropine; D011433:Propranolol; D000242:Cyclic AMP; D005947:Glucose; D012413:Rubidium; D002118:Calcium; D011224:Prazosin; D004837:Epinephrine