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

FEBS Letters

Efanov, Alexander M¹  Gromada, Jesper¹  Wollheim, Claes B²  Berggren, Per-Olof³  Høy, Marianne¹  Maechler, Pierre² 

[1] Islet Discovery Research, Novo Nordisk A/S, Novo Alle, 2880 Bagsvaerd, Denmark;Division of Clinical Biochemistry, Department of Internal Medicine, University Medical Center, Geneva, Switzerland;The Rolf Luft Center for Diabetes Research, Department of Molecular Medicine, Karolinska Institutet, Karolinska Hospital L3, 171 76 Stockholm, Sweden

关键词: Glutamate;    Exocytosis;    Insulin;    Beta cell;    [Ca2+]i;    cytoplasmic-free Ca2+ concentration;    GDH;    glutamate dehydrogenase;    TCA;    tricarboxylic acid;   

DOI  :  10.1016/S0014-5793(02)03500-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown