Specificity of divalent cation requirement for insulin release

Abstract

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 differences between both cations are due to non identical membrane transport and unequal activation of later steps of the stimulus-secretion coupling.