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.

Glucose-inhibition of glucagon secretion involves activation of GABAA-receptor chloride channels

Abstract

THE endocrine part of the pancreas plays a central role in blood-glucose regulation. It is well established that an elevation of glucose concentration reduces secretion of the hyperglycaemia-associated hormone glucagon from pancreatic α2 cells. The mechanisms involved, however, remain unknown. Electrophysio-logical studies have demonstrated that α2 cells generate Ca2+-dependent action potentials. The frequency of these action poten-tials, which increases under conditions that stimulate glucagon release, is not affected by glucose or insulin1. The inhibitory neurotransmitter γ-aminobutyric acid (GABA) is present in the endocrine part of the pancreas at concentrations comparable to those encountered in the central nervous system2, and co-localizes with insulin in pancreatic β cells3. We now describe a mechanism whereby GABA, co-secreted with insulin from β cells, may mediate part of the inhibitory action of glucose on glucagon secretion by activating GABAA-receptor Cl channels in α2 cells. These observations provide a model for feedback regulation of glucagon release, which may be of significance for the understanding of the hypersecretion of glucagon frequently associated with diabetes4.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Rorsman, P. & Hellman, B. J. gen. Physiol. 91, 223–242 (1988).

    CAS  Article  Google Scholar 

  2. 2

    Okada, Y., Tanigushi, H. & Shimada, C. Science 194, 620–622 (1979).

    ADS  Article  Google Scholar 

  3. 3

    Garry, D. J., Sorenson, L., Elde, R. P., Maley, B. E. & Madsen, A. Diabetes 35, 1090–1096 (1986).

    CAS  Article  Google Scholar 

  4. 4

    Lins, P. E., Wajngot, A., Adamsson, U., Vranic, M. & Efendic, S. Diabetes 32, 633–635 (1983).

    CAS  Article  Google Scholar 

  5. 5

    Robbins, M. S., Grouse, L. H., Sorenson, R. L. & Elde, R. P. Diabetes 30, 168–171 (1981).

    CAS  Article  Google Scholar 

  6. 6

    Bormann, J., Hamill, O. P. & Sakmann, B. J. Physiol. (Lond.) 385, 243–286 (1987).

    CAS  Article  Google Scholar 

  7. 7

    Bormann, J. & Clapham, D. E. Proc. natn. Acad Sci. U.S.A. 82, 2168–2172 (1985).

    ADS  CAS  Article  Google Scholar 

  8. 8

    Vicini, S., Mienville, J. M. & Costa, E. J. Pharmac. exp. Therap. 243, 1195–1201 (1987).

    CAS  Google Scholar 

  9. 9

    Taleb, O. et al. Pflügers Arch. ges. Physiol. 409, 620–631 (1987).

    CAS  Article  Google Scholar 

  10. 10

    Kehl, S. J., Hughes, D. & McBurney, R. N. Br. J. Pharmac. 92, 573–585 (1987).

    CAS  Article  Google Scholar 

  11. 11

    Akaike, N., Inoue, M. & Krishtal, O. A. J. Physiol. (Lond.) 379, 171–185 (1986).

    CAS  Article  Google Scholar 

  12. 12

    Gerber, J. C. & Hare, T. A. Brain Res. Bull. 5, (suppl. 2), 341–346 (1980).

    CAS  Article  Google Scholar 

  13. 13

    Johansson, H., Gylfe, E. & Hellman, B., Biochem. biophys. Res. Commun. 147, 309–313 (1987).

    CAS  Article  Google Scholar 

  14. 14

    Pipeleers, D. G., Schuit, F. C., Van Schravendijk, C. F. H. & Van De Winkel, M. Endocrinology 117, 817–823 (1985).

    CAS  Article  Google Scholar 

  15. 15

    Faloona, G. R. & Unger, R. H. in Methods of Hormone Radioimmunoassay (eds Jaffe B. M. & Behrman H. R.) 324–326 (Academic, New York, 1974).

    Google Scholar 

  16. 16

    McLean, I. W. & Nakane, P. K. J. Histochem. Cytochem. 22, 1077–1083 (1974).

    CAS  Article  Google Scholar 

  17. 17

    Scoch, P. et al. Nature 314, 168–171 (1985).

    ADS  Article  Google Scholar 

  18. 18

    Häring, P. et al. Proc. natn. Acad. Sci. U.S.A. 82, 4837–4841 (1985).

    ADS  Article  Google Scholar 

  19. 19

    Schofield, P. R. et al. Nature 328, 221–227 (1987).

    ADS  CAS  Article  Google Scholar 

  20. 20

    Hamill, O. P., Marty, A., Neher, E., Sakmann, B. & Sigworth, F. J. Pflügers Arch. ges. Physiol. 391, 85–100 (1981).

    CAS  Article  Google Scholar 

  21. 21

    Efendic, S., Nylén, A., Roovete, A. & Uvnäs-Wallensten, K. FEBS Lett. 92, 33–35 (1978).

    CAS  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Rorsman, P., Berggren, PO., Bokvist, K. et al. Glucose-inhibition of glucagon secretion involves activation of GABAA-receptor chloride channels. Nature 341, 233–236 (1989). https://doi.org/10.1038/341233a0

Download citation

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

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