title: Exciting Times for Pancreatic Islets: Glutamate Signaling in Endocrine Cells.
abstract: 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.
authors.affiliation: Institute of Metabolic Physiology, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany; Institute for Beta Cell Biology, German Diabetes Center (DDZ), Leibniz Center for Diabetes Research, and German Center for Diabetes Research (DZD e.V.), Düsseldorf, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Otter
authors.affiliation: Institute of Metabolic Physiology, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany; Institute for Beta Cell Biology, German Diabetes Center (DDZ), Leibniz Center for Diabetes Research, and German Center for Diabetes Research (DZD e.V.), Düsseldorf, Germany. Electronic address: lammert@hhu.de.
authors.forename: Eckhard
authors.initials: E
authors.lastname: Lammert
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D018698:Glutamic Acid / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008954:Models, Biological; D017470:Receptors, Glutamate / Q000737:chemistry / Q000378:metabolism; D015290:Second Messenger Systems / Q000187:drug effects; D022142:Secretory Vesicles / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D007004:Hypoglycemic Agents; D007328:Insulin; D017470:Receptors, Glutamate; D018698:Glutamic Acid
keywords: NMDA receptor; diabetes mellitus; drug; glutamate; insulin secretion; pancreatic beta cell