| 1. |
- Barg, Sebastian, 1969-, et al.
(författare)
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Granule docking and cargo release in pancreatic β-cells
- 2008
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Ingår i: Biochemical Society Transactions. - 0300-5127 .- 1470-8752. ; 36:Pt 3, s. 294-299
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Tidskriftsartikel (refereegranskat)abstract
- Biphasic insulin secretion is required for proper insulin action and is observed not only in vivo, but also in isolated pancreatic islets and even single beta-cells. Late events in the granule life cycle are thought to underlie this temporal pattern. In the last few years, we have therefore combined live cell imaging and electrophysiology to study insulin secretion at the level of individual granules, as they approach the plasma membrane, undergo exocytosis and finally release their insulin cargo. In the present paper, we review evidence for two emerging concepts that affect insulin secretion at the level of individual granules: (i) the existence of specialized sites where granules dock in preparation for exocytosis; and (ii) post-exocytotic regulation of cargo release by the fusion pore.
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| 2. |
- Obermüller, Stefanie, et al.
(författare)
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Defective secretion of islet hormones in chromogranin-B deficient mice
- 2010
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:1, s. e8936-
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Tidskriftsartikel (refereegranskat)abstract
- Granins are major constituents of dense-core secretory granules in neuroendocrine cells, but their function is still a matter of debate. Work in cell lines has suggested that the most abundant and ubiquitously expressed granins, chromogranin A and B (CgA and CgB), are involved in granulogenesis and protein sorting. Here we report the generation and characterization of mice lacking chromogranin B (CgB-ko), which were viable and fertile. Unlike neuroendocrine tissues, pancreatic islets of these animals lacked compensatory changes in other granins and were therefore analyzed in detail. Stimulated secretion of insulin, glucagon and somatostatin was reduced in CgB-ko islets, in parallel with somewhat impaired glucose clearance and reduced insulin release, but normal insulin sensitivity in vivo. CgB-ko islets lacked specifically the rapid initial phase of stimulated secretion, had elevated basal insulin release, and stored and released twice as much proinsulin as wildtype (wt) islets. Stimulated release of glucagon and somatostatin was reduced as well. Surprisingly, biogenesis, morphology and function of insulin granules were normal, and no differences were found with regard to beta-cell stimulus-secretion coupling. We conclude that CgB is not required for normal insulin granule biogenesis or maintenance in vivo, but is essential for adequate secretion of islet hormones. Consequentially CgB-ko animals display some, but not all, hallmarks of human type-2 diabetes. However, the molecular mechanisms underlying this defect remain to be determined.
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| 3. |
- Obermüller, Stefanie, et al.
(författare)
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Selective nucleotide-release from dense-core granules in insulin-secreting cells.
- 2005
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Ingår i: Journal of Cell Science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 118:Pt 18, s. 4271-4282
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Tidskriftsartikel (refereegranskat)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 similar to 0.1 and similar to 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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