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Pancreatic β-cell function is essential for the regulation of glucose homeostasis and its impairment leads to diabetes mellitus. Besides glucose, the major nutrient factor, inputs from neural and humoral components and intraislet cell–cell communication act together to guarantee an appropriate pancreatic β-cell function. Data obtained over the last 5 years in several laboratories have revitalized a controversial concept, namely the autocrine feedback action of secreted insulin on β-cell function. While, historically, insulin was suggested to exert a negative effect on β-cells, recent data provide evidence for a positive role of insulin in transcription, translation, ion flux, insulin secretion and β-cell survival. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]