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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Glutamate is a positive autocrine signal for glucagon release.
Cell Metab. 7, 545-554 (2008)
An important feature of glucose homeostasis is the effective release of glucagon from the pancreatic alpha cell. The molecular mechanisms regulating glucagon secretion are still poorly understood. We now demonstrate that human alpha 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 alpha 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 alpha 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.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
ISSN (print) / ISBN
1550-4131
e-ISSN
1932-7420
Zeitschrift
Cell Metabolism
Quellenangaben
Band: 7,
Heft: 6,
Seiten: 545-554
Verlag
Elsevier
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Pancreatic Islet Research (IPI)