Specificity of divalent cation requirement for insulin release. Effects of strontium

Isolated pancreatic islets of rats were used to investigate whether Sr2+ can effectively replace Ca2+ in sustaining insulin release. Insulin secretion in response to glucose, potassium and tolbutamide was lower in a Sr2+ than in a Ca2+ medium, even at the optimum concentration of 2.5 mmol/l. The amplitude of the second phase of glucose-induced release was inversely related to the duration of Ca2+ replacement by Sr2+. The insulinotropic effect of glucose was suppressed by Co2+ and D600 in a Sr2+ medium and also reduced by addition of Sr2+ itself to a Ca2+ medium. Glucose uptake, glucose utilization and K-permeability in islet cells were not altered by Sr2+ substitution for Ca2+. The basal uptake of Sr2+ was lower than that of Ca2+, but was increased by glucose or high K+, Co2+ and Ca2+ inhibited Sr2+ uptake more markedly than Co2+ and Sr2+ inhibited Ca2+ uptake. High glucose reduced Sr2+ efflux from islet cells less markedly than Ca2+ efflux. These results show that Sr2+ is less effective than Ca2+ in sustaining insulin release and suggest that the difference between both cations are due to non identical membrane transport and unequal activation of later steps of the stimulus-secretion coupling.