Sökning: onr:"swepub:oai:prod.swepub.kib.ki.se:145437100" > XPR1 Mediates the P...
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000 | 02842naa a2200373 4500 | |
001 | oai:prod.swepub.kib.ki.se:145437100 | |
003 | SwePub | |
008 | 240920s2021 | |||||||||||000 ||eng| | |
024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1454371002 URI |
024 | 7 | a https://doi.org/10.2337/db19-06332 DOI |
040 | a (SwePub)ki | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Barker, CJu Karolinska Institutet4 aut |
245 | 1 0 | a XPR1 Mediates the Pancreatic β-Cell Phosphate Flush |
264 | c 2020-08-21 | |
264 | 1 | b American Diabetes Association,c 2021 |
520 | a Glucose-stimulated insulin secretion is the hallmark of the pancreatic β-cell, a critical player in the regulation of blood glucose concentration. In 1974, the remarkable observation was made that an efflux of intracellular inorganic phosphate (Pi) accompanied the events of stimulated insulin secretion. The mechanism behind this “phosphate flush,” its association with insulin secretion, and its regulation have since then remained a mystery. We recapitulated the phosphate flush in the MIN6m9 β-cell line and pseudoislets. We demonstrated that knockdown of XPR1, a phosphate transporter present in MIN6m9 cells and pancreatic islets, prevented this flush. Concomitantly, XPR1 silencing led to intracellular Pi accumulation and a potential impact on Ca2+ signaling. XPR1 knockdown slightly blunted first-phase glucose-stimulated insulin secretion in MIN6m9 cells, but had no significant impact on pseudoislet secretion. In keeping with other cell types, basal Pi efflux was stimulated by inositol pyrophosphates, and basal intracellular Pi accumulated following knockdown of inositol hexakisphosphate kinases. However, the glucose-driven phosphate flush occurred despite inositol pyrophosphate depletion. Finally, while it is unlikely that XPR1 directly affects exocytosis, it may protect Ca2+ signaling. Thus, we have revealed XPR1 as the missing mediator of the phosphate flush, shedding light on a 45-year-old mystery. | |
700 | 1 | a Tessaro, FHG4 aut |
700 | 1 | a Ferreira, SD4 aut |
700 | 1 | a Simas, R4 aut |
700 | 1 | a Ayala, TS4 aut |
700 | 1 | a Kohler, Mu Karolinska Institutet4 aut |
700 | 1 | a Rajasekaran, SS4 aut |
700 | 1 | a Martins, JO4 aut |
700 | 1 | a Dare, Eu Karolinska Institutet4 aut |
700 | 1 | a Berggren, POu Karolinska Institutet4 aut |
710 | 2 | a Karolinska Institutet4 org |
773 | 0 | t Diabetesd : American Diabetes Associationg 70:1, s. 111-118q 70:1<111-118x 1939-327Xx 0012-1797 |
856 | 4 | u https://diabetesjournals.org/diabetes/article-pdf/70/1/111/437815/db190633.pdf |
856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:145437100 |
856 | 4 8 | u https://doi.org/10.2337/db19-0633 |
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