{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T19:11:29Z","timestamp":1793214689774,"version":"4.5.0"},"reference-count":45,"publisher":"National Academy of Sciences","issue":"15","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,4,10]]},"abstract":"<jats:p>\n                    There is widespread interest in defining factors and mechanisms that stimulate proliferation of pancreatic islet cells. Wnt signaling is an important regulator of organ growth and cell fates, and genes encoding Wnt-signaling factors are expressed in the pancreas. However, it is unclear whether Wnt signaling regulates pancreatic islet proliferation and differentiation. Here we provide evidence that Wnt signaling stimulates islet \u03b2 cell proliferation. The addition of purified Wnt3a protein to cultured \u03b2 cells or islets promoted expression of Pitx2, a direct target of Wnt signaling, and Cyclin D2, an essential regulator of \u03b2 cell cycle progression, and led to increased \u03b2 cell proliferation\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Conditional pancreatic \u03b2 cell expression of activated \u03b2-catenin, a crucial Wnt signal transduction protein, produced similar phenotypes\n                    <jats:italic>in vivo<\/jats:italic>\n                    , leading to \u03b2 cell expansion, increased insulin production and serum levels, and enhanced glucose handling. Conditional \u03b2 cell expression of Axin, a potent negative regulator of Wnt signaling, led to reduced Pitx2 and Cyclin D2 expression by \u03b2 cells, resulting in reduced neonatal \u03b2 cell expansion and mass and impaired glucose tolerance. Thus, Wnt signaling is both necessary and sufficient for islet \u03b2 cell proliferation, and our study provides previously unrecognized evidence of a mechanism governing endocrine pancreas growth and function.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0701509104","type":"journal-article","created":{"date-parts":[[2007,4,2]],"date-time":"2007-04-02T21:04:22Z","timestamp":1175547862000},"page":"6247-6252","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":302,"title":["Wnt signaling regulates pancreatic \u03b2 cell proliferation"],"prefix":"10.1073","volume":"104","author":[{"given":"Ingrid C.","family":"Rulifson","sequence":"first","affiliation":[{"name":"Departments of *Developmental Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satyajit K.","family":"Karnik","sequence":"additional","affiliation":[{"name":"Departments of *Developmental Biology 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