Cobalt inhibition of insulin secretion and calcium uptake by isolated rat islets

Cobalt (Co'++) inhibited glucose-, leucine-, and K'+-induced immunoreactive insulin (IRI)release by isolated rat islets. This inhibition of the insulinotropic effect of glucose was dose dependent, affected both phases of secretion, was very rapid, and was well reversible. It exhibited a kinetics similiar to that of Ca'++ omission, and the metal (2.5 mM) prevented Ca'++ reintroduction from restoring a normal rate of IRI release. Theophylline (2 mM) partially overcame the inhibitory effect of 0.5 mM Co'++, but not that of 2.5 mM. Glucose-induced secretion was lessmarkedly reduced by 0.5 mM Co'++ in the absence of Mg'++ or in the presence of 7.5 mM Ca'++. Even at 12.5 mM, the metal did not alter glucose oxidation by theislets. By contrast, Ca uptake by islet cells was reversibly diminished (55%) in the presence of 1.25 mM Co'++. Calcium influx (measured after 2.5 min) was aslo reduced by Co'++ to a degree that did not change after longer incubation periods. It is concluded that Co'++ inhibits IRI release mainly through an antaognistic action on Ca entry in beta cells.