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First published online 1 September 2005
doi: 10.1242/jcs.02549
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Research Article |
1 Department of Experimental Medicinal Sciences, Lund University, BMC B11, SE-221 84 Lund, Sweden
2 OCDEM, Nuffield Department of Clinical Medicine, University of Oxford, Churchill Hospital, Oxford, OX3 7LJ, UK
3 Vollum Institute, Oregon Health and Sciences University, 3181 SW Sam Jackson Park Road, Portland OR, 97210, USA
* Author for correspondence (e-mail: bargs{at}ohsu.edu)
Accepted 17 June 2005
Secretory granules of insulin-secreting cells are used to store and release peptide hormones as well as low-molecular-weight compounds such as nucleotides. Here we have compared the rate of exocytosis with the time courses of nucleotide and peptide release by a combination of capacitance measurements, electrophysiological detection of ATP release and single-granule imaging. We demonstrate that the release of nucleotides and peptides is delayed by 
0.1 and 2 seconds with respect to membrane fusion, respectively. We further show that in up to 70% of the cases exocytosis does not result in significant release of the peptide cargo, likely because of a mechanism that leads to premature closure of the fusion pore. Release of nucleotides and protons occurred regardless of whether peptides were secreted or not. These observations suggest that insulin-secreting cells are able to use the same secretory vesicles to release small molecules either alone or together with the peptide hormone.
Key words: Exocytosis, Endocytosis, Fusion pore, Insulin, Hormone, Kiss-and-run, Secretion
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