Increase in cellular glutamate levels stimulates exocytosis in pancreatic β‐cells

Abstract

Glutamate has been implicated as an intracellular messenger in the regulation of insulin secretion in response to glucose. Here we demonstrate by measurements of cell capacitance in rat pancreatic β‐cells that glutamate (1 mM) enhanced Ca²⁺‐dependent exocytosis. Glutamate (1 mM) also stimulated insulin secretion from permeabilized rat β‐cells. The effect was dose‐dependent (half‐maximum at 5.1 mM) and maximal at 10 mM glutamate. Glutamate‐induced exocytosis was stronger in rat β‐cells and clonal INS‐1E cells compared to β‐cells isolated from mice and in parental INS‐1 cells, which correlated with the expressed levels of glutamate dehydrogenase. Glutamate‐induced exocytosis was inhibited by the protonophores FCCP and SF6847, by the vacuolar‐type H⁺‐ATPase inhibitor bafilomycin A₁ and by the glutamate transport inhibitor Evans Blue. Our data provide evidence that exocytosis in β‐cells can be modulated by physiological increases in cellular glutamate levels. The results suggest that stimulation of exocytosis is associated with accumulation of glutamate in the secretory granules, a process that is dependent on the transgranular proton gradient.