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Biddle Family Foundation"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The islet \u03b2-cells integrate external signals to modulate insulin secretion to better regulate blood glucose levels during periods of changing metabolic demand. The vesicular monoamine transporter type 2 (VMAT2), an important regulator of CNS neurotransmission, has an analogous role in the endocrine pancreas as a key control point of insulin secretion, with additional roles in regulating \u03b2-cell differentiation and proliferation. Here we report on the synthesis and biological characterisation of a fluorescent ligand for VMAT2 suitable for live cell imaging. Staining for VMAT2 and dopamine in live \u03b2-cell cultures show colocalisation in specific vesicles and reveal a heterogeneous population with respect to cell size, shape, vesicle number, size, and contents. Staining for VMAT2 and zinc ion, as a surrogate for insulin, reveals a wide range of vesicle sizes. Immunohistochemistry shows larger \u03b2-cell vesicles enriched for proinsulin, whereas smaller vesicles predominantly contain the processed mature insulin. In \u03b2-cell cultures obtained from nondiabetic donors, incubation at non-stimulatory glucose concentrations promotes a shift in vesicle diameter towards the more mature insulin vesicles at the expense of the larger immature insulin secretory vesicle population. We anticipate that this probe will be a useful reagent to identify living \u03b2-cells within complex mixtures for further manipulation and characterisation.<\/jats:p>","DOI":"10.1038\/s41598-019-41891-x","type":"journal-article","created":{"date-parts":[[2019,4,1]],"date-time":"2019-04-01T11:29:55Z","timestamp":1554118195000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A novel optical tracer for VMAT2 applied to live cell measurements of vesicle maturation in cultured human \u03b2-cells"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3706-8768","authenticated-orcid":false,"given":"Stevan","family":"Pecic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nenad","family":"Milosavic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina","family":"Rayat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5637-6523","authenticated-orcid":false,"given":"Antonella","family":"Maffei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4806-8242","authenticated-orcid":false,"given":"Paul E.","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,4,1]]},"reference":[{"issue":"Suppl 1","key":"41891_CR1","doi-asserted-by":"publisher","first-page":"S27","DOI":"10.1016\/S0168-8227(11)70010-9","volume":"93","author":"JC Henquin","year":"2011","unstructured":"Henquin, J. 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