Journal
IUBMB LIFE
Volume 50, Issue 1, Pages 27-31Publisher
WILEY
DOI: 10.1080/15216540050176557
Keywords
exocytosis; glutamate dehydrogenase; insulin; oxygen consumption; succinate
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The mitochondria play a pivotal role in regulating glucose-induced insulin secretion in the pancreatic beta cell. We have recently demonstrated that glutamate derived from mitochondria participates directly in the stimulation of insulin exocytosis, Tn the present study, mitochondria isolated from the beta cell line INS-1E generated glutamate when incubated with the tricarboxylic acid cycle intermediate succinate, The generation of glutamate correlated with stimulated mitochondrial activity monitored as oxygen consumption and was inhibited by the mitochondrial uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone. Glutamate is formed by the mitochondrial enzyme glutamate dehydrogenase from cr-ketoglutarate. Transient overexpression of glutamate dehydrogenase in INS-1E cells resulted in potentiation of glucose-stimulated hormone secretion without affecting basal release, These results further point to glutamate as an intracellular messenger playing a key role in the control of insulin exocytosis.
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