{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:42:50Z","timestamp":1761871370645,"version":"build-2065373602"},"reference-count":36,"publisher":"Wiley","issue":"s3","license":[{"start":{"date-parts":[[2012,8,28]],"date-time":"2012-08-28T00:00:00Z","timestamp":1346112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:p>\n                    Ca\n                    <jats:sup>2+<\/jats:sup>\n                    extrusion from the \u03b2\u2010cell is mediated by two processes the Na\/Ca exchanger (NCX)  and the plasma membrane Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010\n                    <jats:styled-content style=\"fixed-case\">ATPase<\/jats:styled-content>\n                    (\n                    <jats:styled-content style=\"fixed-case\">PMCA<\/jats:styled-content>\n                    ). Gain of function studies show that overexpression of\n                    <jats:styled-content style=\"fixed-case\">NCX<\/jats:styled-content>\n                    or\n                    <jats:styled-content style=\"fixed-case\">PMCA<\/jats:styled-content>\n                    leads to endoplasmic reticulum (\n                    <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content>\n                    ) Ca\n                    <jats:sup>2+<\/jats:sup>\n                    depletion with subsequent\n                    <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content>\n                    stress, decrease in \u03b2\u2010cell proliferation and \u03b2\u2010cell death by apoptosis. Interestingly, chronic exposure to cytokines or high free fatty acid concentrations also induce\n                    <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content>\n                    Ca\n                    <jats:sup>2+<\/jats:sup>\n                    depletion and \u03b2\u2010cell death in diabetes. Loss of function studies show, on the contrary, that heterozygous inactivation of\n                    <jats:styled-content style=\"fixed-case\">NCX1<\/jats:styled-content>\n                    (\n                    <jats:italic>\n                      Ncx1\n                      <jats:sup>+\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    ) leads to an increase in \u03b2\u2010cell function (insulin production and release), and a fivefold increase in both \u03b2\u2010cell mass and proliferation. The mutation also increases \u03b2\u2010cell resistance to hypoxia, and\n                    <jats:italic>\n                      Ncx1\n                      <jats:sup>+\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    islets show a two to four times higher rate of diabetes cure than Ncx1\n                    <jats:sup>+\/+<\/jats:sup>\n                    islets when transplanted in diabetic animals. Thus, down\u2010regulation of the Na\/Ca exchanger leads to various changes in \u03b2\u2010cell function that are opposite to the major abnormalities seen in diabetes. This provides a unique model for the prevention and treatment of \u03b2\u2010cell dysfunction in diabetes and following islet transplantation.\n                  <\/jats:p>","DOI":"10.1111\/j.1463-1326.2012.01649.x","type":"journal-article","created":{"date-parts":[[2012,8,28]],"date-time":"2012-08-28T08:47:45Z","timestamp":1346143665000},"page":"136-142","source":"Crossref","is-referenced-by-count":22,"title":["\u03b2\u2010Cell preservation and regeneration in diabetes by modulation of \u03b2\u2010cell\n                    <scp>Ca<\/scp>\n                    <sup>2+<\/sup>\n                    homeostasis"],"prefix":"10.1111","volume":"14","author":[{"given":"A.","family":"Herchuelz","sequence":"first","affiliation":[{"name":"Laboratoire de Pharmacodynamie et de Th\u00e9rapeutique Universit\u00e9 Libre de Bruxelles (ULB), Facult\u00e9 de M\u00e9dicine  B\u20101070 Brussels 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