Heterogeneity of β-Cell Secretion

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


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.


Plaque Assay Plaque Size Patch Clamp Experiment Large Plaque Small Plaque 
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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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