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

Journal article

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: Obermüller, S; Lindqvist, A; Karanauskaite, J; Galvanovskis, J; Rorsman, P

• Publication status: Published
• Journal: Journal of cell science
• Volume: 118
• Issue: Pt 18
• Pages: 4271-4282
• Publication date: 2005-09-01
• DOI: 10.1242/jcs.02549
• EISSN: 1477-9137
• ISSN: 0021-9533
• Language: English
• Keywords: Islet Amyloid Polypeptide; Receptors, Purinergic P2X2; Islets of Langerhans; Peptides; Membrane Potentials; Adenine Nucleotides; Hydrogen-Ion Concentration; Insulin; Amyloid; Receptors, Purinergic P2; Time Factors; Secretory Vesicles; Cells, Cultured; Adenosine Triphosphate; Exocytosis; Transfection