Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • News & Views
  • Published:

Cell biology

Glutamate primes the pump

Nature volume 402, pages 595–596 (1999)Cite this article

Glutamate is the most widely distributed excitatory neurotransmitter in the central nervous system. It is stored within nerve terminals, in small vesicles that are released when the nerve cell is stimulated. Once released, glutamate diffuses to neighbouring nerve cells where it binds to glutamate receptors, resulting in an influx of sodium and calcium ions (ionotropic receptors) or mobilization of intracellular calcium (metabotropic receptors). On page 685 of this issue, Maechler and Wollheim1 report that, as well as having an extracellular function in neurotransmission, glutamate acts as an intracellular signal. They show that in insulin-secreting pancreatic β-cells, glutamate is involved in preparing the insulin-filled secretory granules for release — a process commonly referred to as ‘priming’.

The two phases of insulin secretion are thought to reflect the sequential release of two functional subsets of secretory granules3. In this model, the rapid release and depletion of a readily releasable pool of granules (RRP), containing only about 50 of the cell's 13,000 or so secretory granules, accounts for the first phase. The second, slower phase reflects the time-dependent replenishment of this pool by priming of granules originally in the reserve pool. Priming proceeds at a rate of 5–10 granules per minute per β-cell, and probably involves a product of cell metabolism because this phase is evoked only by stimuli that can be metabolized (such as glucose), and not by agents that merely increase the levels of intracellular calcium3. It has not been possible to establish the identity of this factor, but Maechler and Wollheim1 now propose that glutamate, generated by amination of the Krebs-cycle intermediate α-ketoglutarate, is the elusive metabolic signal.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Biphasic stimulation of insulin secretion in response to glucose.
Figure 2: Model to account for the effects of glutamate on granule priming, based, in part, on the results of Maechler and Wollheim1.

References

  1. Maechler, P. & Wollheim, C. B. Nature 402, 685–689 (1999).

    Article  ADS  CAS  Google Scholar 

  2. Curry, D. L., Bennett, L. L. & Grodsky, G. M. Endocrinology 83, 572–584 (1968).

    Article  CAS  Google Scholar 

  3. Eliasson, L. et al. J. Physiol. 503, 399–412 (1997).

    Article  CAS  Google Scholar 

  4. Hanson, P. I., Heuser, J. E. & Jahn, R. Curr. Opin. Neurobiol. 7, 310–315 (1997).

    Article  CAS  Google Scholar 

  5. Lang, J. Eur. J. Biochem. 259, 3–17 (1999).

    Article  CAS  Google Scholar 

  6. Kiraly-Borri, C. et al. Biochem. J. 314, 199–203 (1996).

    Article  CAS  Google Scholar 

  7. Özkam, E. D. & Ueda, T. Jpn. J. Pharmacol. 77, 1–10 (1998).

    Article  Google Scholar 

  8. Weaver, C. D., Yao, T. L., Powers, A. C. & Verdoorn, T. A. J. Biol. Chem. 271, 12977–12984 (1996).

    Article  CAS  Google Scholar 

  9. Zoccarato, F., Cavallini, L. & Alexandre, A. J. Neurochem. 72, 625–633 (1999).

    Article  CAS  Google Scholar 

  10. Ungerman, C., Wickner, W. & Xu, Z. Proc. Natl Acad. Sci. USA 96, 11194–11199 (1999).

    Article  ADS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. the Department of Molecular and Cellular Physiology, Lund University, Sölvegatan 19, Lund, S-223 62, Sweden

    Patrik Rorsman & Erik Renström

Authors
  1. Patrik Rorsman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Erik Renström
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Patrik Rorsman.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rorsman, P., Renström, E. Glutamate primes the pump. Nature 402, 595–596 (1999). https://doi.org/10.1038/45110

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/45110

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing