title: Selective nucleotide-release from dense-core granules in insulin-secreting cells.
abstract: 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 approximately 0.1 and approximately 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.
authors.affiliation: Department of Experimental Medicinal Sciences, Lund University, BMC B11, SE-221 84 Lund, Sweden.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Obermüller
authors.forename: Anders
authors.initials: A
authors.lastname: Lindqvist
authors.forename: Jovita
authors.initials: J
authors.lastname: Karanauskaite
authors.forename: Juris
authors.initials: J
authors.lastname: Galvanovskis
authors.forename: Patrik
authors.initials: P
authors.lastname: Rorsman
authors.forename: Sebastian
authors.initials: S
authors.lastname: Barg
mesh_terms: D000227:Adenine Nucleotides / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000682:Amyloid / Q000378:metabolism; D002478:Cells, Cultured; D005089:Exocytosis / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology; D010455:Peptides / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058476:Receptors, Purinergic P2X2; D022142:Secretory Vesicles / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection
chemical_list: D000227:Adenine Nucleotides; D000682:Amyloid; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D010455:Peptides; D018048:Receptors, Purinergic P2; D058476:Receptors, Purinergic P2X2; D000255:Adenosine Triphosphate