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JCS ePress online publication date 1 Sep 2005
doi: 10.1242/jcs.02549

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Research Article

Selective nucleotide-release from dense-core granules in insulin-secreting cells


Stefanie Obermüller, Anders Lindqvist, Jovita Karanauskaite, Juris Galvanovskis, Patrik Rorsman, and Sebastian Barg*
* Author for correspondence (e-mail: bargs{at}ohsu.edu)

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.
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