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However, much less attention has been paid to the physiologic actions of IAPP on pancreatic \u03b2 cells, which secrete this peptide together with insulin upon glucose stimulation. Here, we aimed to explore the signaling pathways and mitogenic actions of IAPP on \u03b2 cells. We show that IAPP activated Erk1\/2 and v\u2010akt murine thymoma viral oncogene homolog 1 (Akt) at the picomolar range (10\u2010100 pM) in mouse pancreatic islets and MIN6 \u03b2 cells cultured at low glucose concentrations. In contrast, IAPP decreased the induction of these pathways by high glucose levels. Consistently, IAPP induced a 1.7\u2010fold increase of \u03b2\u2010cell proliferation at low\u2010glucose conditions, whereas it reduced \u03b2\u2010cell proliferation at high glucose levels. Strikingly, the specific antagonist of the IAPP receptor AC187 (100 nM) decreased the activation of Erk1\/2 and Akt and reduced \u03b2\u2010cell proliferation by 24% in glucose\u2010stimulated \u03b2 cells, uncovering a key role of endogenously released IAPP in \u03b2\u2010cell responses to glucose. We conclude that exogenously added IAPP exerts a dual effect on \u03b2\u2010cell mitogenic signaling and proliferation, depending on the glucose concentration. Importantly, secreted IAPP contributes to the signaling and mitogenic response of \u03b2 cells to glucose through an autocrine mechanism.\u2014 Visa, M., Alcarraz\u2010Viz\u00e1n, G., Montane, J., Cadavez, L., Casta\u00f1o, C., Villanueva\u2010Pe\u00f1acarrillo, M. L., Servitja, J.\u2010M., Novials, A. Islet amyloid polypeptide exerts a novel autocrine action in \u03b2\u2010cell signaling and proliferation.\n                    <jats:italic>FASEB J<\/jats:italic>\n                    . 29, 2970\u20102979 (2015).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.15-270553","type":"journal-article","created":{"date-parts":[[2015,3,26]],"date-time":"2015-03-26T04:43:53Z","timestamp":1427345033000},"page":"2970-2979","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Islet amyloid polypeptide exerts a novel autocrine action in \u03b2\u2010cell signaling and proliferation"],"prefix":"10.1096","volume":"29","author":[{"given":"Montse","family":"Visa","sequence":"first","affiliation":[{"name":"Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gema","family":"Alcarraz\u2010Viz\u00e1n","sequence":"additional","affiliation":[{"name":"Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Montane","sequence":"additional","affiliation":[{"name":"Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Cadavez","sequence":"additional","affiliation":[{"name":"Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Casta\u00f1o","sequence":"additional","affiliation":[{"name":"Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Luisa","family":"Villanueva\u2010Pe\u00f1acarrillo","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas Barcelona Spain"},{"name":"Department of Metabolism, Nutrition and Hormones Instituto de Investigaci\u00f3n Sanitaria de la Fundaci\u00f3n Jim\u00e9nez D\u00edaz Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan\u2010Marc","family":"Servitja","sequence":"additional","affiliation":[{"name":"Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Novials","sequence":"additional","affiliation":[{"name":"Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,3,25]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.39.5.634"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(91)91325-7"},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1100\/tsw.2006.263","article-title":"Amylin in the periphery II: an updated mini-review","volume":"6","author":"Wookey P. 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