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Glutamate Is a Positive Autocrine Signal for Glucagon Release

2008; Cell Press; Volume: 7; Issue: 6 Linguagem: Inglês

10.1016/j.cmet.2008.03.004

1932-7420

Over Cabrera, Maria C. Jacques-Silva, Stephan Speier, Shao-Nian Yang, Martin Köhler, Alberto Fachado, Elaine Vieira, Juleen R. Zierath, Richard G. Kibbey, Dora M. Berman, Norma S. Kenyon, Camillo Ricordi, Alejandro Caicedo, Per‐Olof Berggren,

Diet and metabolism studies

Summary An important feature of glucose homeostasis is the effective release of glucagon from the pancreatic α cell. The molecular mechanisms regulating glucagon secretion are still poorly understood. We now demonstrate that human α cells express ionotropic glutamate receptors (iGluRs) that are essential for glucagon release. A lowering in glucose concentration results in the release of glutamate from the α cell. Glutamate then acts on iGluRs of the AMPA/kainate type, resulting in membrane depolarization, opening of voltage-gated Ca 2+ channels, increase in cytoplasmic free Ca 2+ concentration, and enhanced glucagon release. In vivo blockade of iGluRs reduces glucagon secretion and exacerbates insulin-induced hypoglycemia in mice. Hence, the glutamate autocrine feedback loop endows the α cell with the ability to effectively potentiate its own secretory activity. This is a prerequisite to guarantee adequate glucagon release despite relatively modest changes in blood glucose concentration under physiological conditions.