Exciting Times for Pancreatic Islets: Glutamate Signaling in Endocrine Cells

Glutamate represents a key excitatory neurotransmitter in the central nervous system, and also modulates the function and viability of endocrine cells in pancreatic islets. In insulin-secreting beta cells, glutamate acts as an intracellular messenger, and its transport into secretory granules promotes glucose- and incretin-stimulated insulin secretion. Mitochondrial degradation of glutamate also contributes to insulin release when glutamate dehydrogenase is allosterically activated. It also signals extracellularly via glutamate receptors (AMPA and NMDA receptors) to modulate glucagon, insulin and somatostatin secretion, and islet cell survival. Its degradation products, GABA and γ-hydroxybutyrate, are released and also influence islet cell behavior. Thus, islet glutamate receptors, such as the NMDA receptors, might serve as possible drug targets to develop new medications for adjunct treatment of diabetes.

TrendsType 2 diabetes and common neurodegenerative diseases share similar pathomechanisms, including excitotoxic cell death.Glutamate, the major excitatory neurotransmitter in the central nervous system, plays an important role in islet cell function and islet cell survival.NMDARs are glutamate receptors that may be potential drug targets for the treatment of type 2 diabetes.Dextromethorphan, an over-the-counter drug and antagonist of NMDARs, has blood glucose lowering effects and increases serum insulin concentrations mainly during the first phase of an oral glucose tolerance test in individuals with type 2 diabetes.