Effects of altered Ca²⁺ and Mg²⁺ concentrations on proliferation and functional differentiation of the clonal insulin-producing cells RINm5F

Effects of calcium and magnesium on proliferation and functional differentiation were investigated in the clonal insulin-producing rat cell line RINm5F. Variations of the extracellular concentrations of Ca²⁺ and Mg²⁺ had only monor effects on the cellular contents of these elements. Even when the medium was depleted of extracellular Ca²⁺ by the addition of EGTA, the Ca Mg ratio corresponded to approximately 0.1. In a Mg²⁺-deficient medium a lowering of the extracellular calcium to 0.13 mM reduced the amount of insulin in the media but increased that in the cells. Irrespective of the concentration of Mg²⁺, depletion of Ca²⁺ was associated with low media levels of insulin and a reduced proliferation rate. In addition, the cells became smaller in size and showed an increased ability to exclude trypan blue. A rise of the magnesium concentration to 6.30 mM was accompanied by a decrease of the cellular content of insulin despite reduced amounts of hormone in the medium. This finding might be due to suppression of insulin biosynthesis, suggesting that the RINm5F cells have a markedly different metabolism and/or sensitivity to extracellular magnesium than non-tumorigenic β-cells.