Glutamate Is a Positive Autocrine Signal for Glucagon Release

Over Cabrera, M. Caroline Jacques-Silva, Stephan Speier, Shao Nian Yang, Martin Köhler, Alberto Fachado, Elaine Vieira, Juleen R. Zierath, Richard Kibbey, Dora Berman-Weinberg, Norma S Kenyon, Camillo Ricordi, Diego A Caicedo-Vierkant, Per Olof Berggren

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

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 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 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.

Original languageEnglish
Pages (from-to)545-554
Number of pages10
JournalCell Metabolism
Volume7
Issue number6
DOIs
StatePublished - Jun 4 2008

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Glucagon
Glutamic Acid
Ionotropic Glutamate Receptors
Glucose
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Kainic Acid
Hypoglycemia
Blood Glucose
Homeostasis
Insulin
Membranes

Keywords

  • HUMDISEASE

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

Cabrera, O., Jacques-Silva, M. C., Speier, S., Yang, S. N., Köhler, M., Fachado, A., ... Berggren, P. O. (2008). Glutamate Is a Positive Autocrine Signal for Glucagon Release. Cell Metabolism, 7(6), 545-554. https://doi.org/10.1016/j.cmet.2008.03.004

Glutamate Is a Positive Autocrine Signal for Glucagon Release. / Cabrera, Over; Jacques-Silva, M. Caroline; Speier, Stephan; Yang, Shao Nian; Köhler, Martin; Fachado, Alberto; Vieira, Elaine; Zierath, Juleen R.; Kibbey, Richard; Berman-Weinberg, Dora; Kenyon, Norma S; Ricordi, Camillo; Caicedo-Vierkant, Diego A; Berggren, Per Olof.

In: Cell Metabolism, Vol. 7, No. 6, 04.06.2008, p. 545-554.

Research output: Contribution to journalArticle

Cabrera, O, Jacques-Silva, MC, Speier, S, Yang, SN, Köhler, M, Fachado, A, Vieira, E, Zierath, JR, Kibbey, R, Berman-Weinberg, D, Kenyon, NS, Ricordi, C, Caicedo-Vierkant, DA & Berggren, PO 2008, 'Glutamate Is a Positive Autocrine Signal for Glucagon Release', Cell Metabolism, vol. 7, no. 6, pp. 545-554. https://doi.org/10.1016/j.cmet.2008.03.004
Cabrera O, Jacques-Silva MC, Speier S, Yang SN, Köhler M, Fachado A et al. Glutamate Is a Positive Autocrine Signal for Glucagon Release. Cell Metabolism. 2008 Jun 4;7(6):545-554. https://doi.org/10.1016/j.cmet.2008.03.004
Cabrera, Over ; Jacques-Silva, M. Caroline ; Speier, Stephan ; Yang, Shao Nian ; Köhler, Martin ; Fachado, Alberto ; Vieira, Elaine ; Zierath, Juleen R. ; Kibbey, Richard ; Berman-Weinberg, Dora ; Kenyon, Norma S ; Ricordi, Camillo ; Caicedo-Vierkant, Diego A ; Berggren, Per Olof. / Glutamate Is a Positive Autocrine Signal for Glucagon Release. In: Cell Metabolism. 2008 ; Vol. 7, No. 6. pp. 545-554.
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