期刊
CELL METABOLISM
卷 7, 期 6, 页码 545-554出版社
CELL PRESS
DOI: 10.1016/j.cmet.2008.03.004
关键词
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资金
- NCRR NIH HHS [U42 RR016603, M01 RR016587, MO1RR16587, 5U42RR016603] Funding Source: Medline
- NIDDK NIH HHS [1R01-DK55347-IU42RR0, R03 DK075487-02, 1R03DK075487, R03 DK075487, U24 DK059635, K08 DK080142, U24 DK59635, R03 DK075487-01] Funding Source: Medline
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 a 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 Ca2+ channels, increase in cytoplasmic free Ca2+ 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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