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Heterogeneity of β-Cell Secretion

Possible Involvement of K-ATP Channels
  • M. Faehling
  • F. M. Ashcroft
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 426)

Abstract

Studies of secretion using the reverse haemolytic plaque assay have revealed a marked heterogeneity in the response of individual β-cells to a given secretagogue concentration (Salomon & Meda, 1986; Hiriart & Matteson, 1988; Hiriart & Ramirez-Medeles, 1991). A similar heterogeneity is also found for the increase in intracellular Ca2+ evoked by glucose (Pralong et al., 1990; Hellman et al., 1992). The rise in [Ca2+]i which stimulates insulin secretion is brought about by activation of voltage-gated Ca2+ channels, as a consequence of the membrane depolarisation which is produced by glucose-induced closure of ATP-sensitive K+ channels (Ashcroft & Rorsman, 1989). Thus, one possible explanation for the heterogeneity observed in both the Ca2+ and the secretory responses of the β-cell to glucose is that they arise from variability in the extent of inhibition of the ATP-sensitive K+ channel (K-ATP channel) by glucose metabolism. No difference in the maximum amplitude of K-ATP currents in β-cells with low and high secretory activity, identified by small and large plaque formation in the reverse haemolytic plaque assay, was found using the standard whole-cell patch-clamp method (Soria et al., 1991). However, these experiments measured the total K-ATP current in the absence of ATP, and did not address the question of whether heterogeneity in the metabolic regulation of the K-ATP channel might underlie the observed secretory variability. In this study, we have used the perforated patch configuration, in which metabolism is preserved, to examine this possibility.

Keywords

Plaque Assay Plaque Size Patch Clamp Experiment Large Plaque Small Plaque 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Ashcroft F. M. and Rorsman P. (1989) Electrophysiology of the pancreatic β-cell. Prog. Biophys. Molec. Biol. 54: 87–143.CrossRefGoogle Scholar
  2. Ashcroft F.M. Harrison D.E. and Ashcroft S.J.H. (1988) Properties of single potassium channels modulated by glucose in rat pancreatic β-cells. J. Physiol. 400: 501–527.PubMedGoogle Scholar
  3. Cohen A. S., Matteson D. R., Parsey R. V. and Sala S. (1990) Ionic currents in rat pancreatic β-cells recorded with the perforated patch technique. Biophys. J. 57: 509a.Google Scholar
  4. Hellman B., Gylfe E., Grappengeisser E., Lund P. E. and Marcström A. (1992) Cytoplasmic calcium and insulin secretion. In Nutrient Regulation of Insulin Secretion. Ed. P. Flatt. pp. 213-246.Google Scholar
  5. Hiriart M. and Matteson D. R. (1988) Na channels and two types of Ca channels in rat pancreatic β-cells identified with the reverse haemolytic plaque assay. J. Gen. Physiol. 91: 617–639.PubMedCrossRefGoogle Scholar
  6. Hiriart M. and Ramirez-Medeles M. C. (1991) Functional subpopulations of individual pancreatic β-cells in culture. Endocrinol. 128: 3193–3198.CrossRefGoogle Scholar
  7. Lewis C., Clark A., Ashcroft S. J. H., Cooper G. J. S. and Morris J. F. (1988) Calcitonin gene-related peptide and somatostatin inhibit insulin release from individual rat β-cells. Mol. Cell. Endocrinol. 57: 41–49.PubMedCrossRefGoogle Scholar
  8. Pipeleers D., Kiekens R, and In’t veld P. (1992) Morphology of the pancreatic β-cell. In Insulin: Molecular Biology to Pathology. Ed. Ashcroft F. M. and Ashcroft S. J. H. pp. 5-33.Google Scholar
  9. Pralong W. F., Bartley C. and Wollheim C. B. (1990) Single islet beta-cell stimulation by nutrients: relationship between pyridine nucleotides, cytosolic Ca2+ and secretion. EMBO J. 9: 53–60.PubMedGoogle Scholar
  10. Rorsman P. and Trube G. (1985). Glucose-dependent K+ channels in pancreatic β-cells are regulated by intracellular ATP. Pflügers Arch. 405: 305–309.PubMedCrossRefGoogle Scholar
  11. Salomon D. and Meda P. (1986) Heterogeneity and contact-dependent regulation of hormone secretion by individual β-cells. Exp. Cell. Res. 162: 507–520.PubMedCrossRefGoogle Scholar
  12. Schuit F. C., In’t Veld P.A., Pipeleers D.G. (1988) Glucose stimulates proinsulin biosynthesis by a dose-dependent recruitment of p ancreatic β-cells. Proc. Natl Acad. Sci. U.S.A. 85: 3865–3869.PubMedCrossRefGoogle Scholar
  13. Soria B., Chanson M., Giordano E., Bosco D. and Meda P. (1991) Ion channels of glucose-responsive and un-responsive cells. Diabetes 40: 1069–1078.PubMedCrossRefGoogle Scholar
  14. Smith P. A., Rorsman P. and Ashcroft F. M. (1990) Simultaneous recording of glucose-dependent electrical activity and ATP-regulated K+-currents in isolated mouse pancreatic β-cells. FEBS Lett. 261: 187–190.PubMedCrossRefGoogle Scholar
  15. Smith P. A. (1988) Electrophysiology of β-cells from pancreatic islets of Langerhans. Ph.D. thesis, University of East Anglia.Google Scholar
  16. Smith P. A., Ashcroft F. M. and Fewtrell C. M. S. (1993) Permeation and gating properties of the L-type calcium channel in mouse pancreatic β-cells. J. Gen. Physiol. 101: 767–797.PubMedCrossRefGoogle Scholar
  17. Trube G., Rorsman P. and Ohno-Shosaku T. (1986). Opposite effects of tolbutamide and diazoxide on the ATP-dependent K+ channel in mouse pancreatic β-cells. Pflügers Arch. 407: 493–499.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • M. Faehling
    • 1
  • F. M. Ashcroft
    • 1
  1. 1.University Laboratory of PhysiologyOX1 3PTUK

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