{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:36:31Z","timestamp":1790663791616,"version":"4.1.0"},"reference-count":50,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T00:00:00Z","timestamp":1728604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades of Spain","award":["RTI2018-095615-B-I00"],"award-info":[{"award-number":["RTI2018-095615-B-I00"]}]},{"name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades of Spain","award":["PID2021-123865OB-I00"],"award-info":[{"award-number":["PID2021-123865OB-I00"]}]},{"name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades of Spain","award":["S2017\/BMD-3684 MOIR2-CM"],"award-info":[{"award-number":["S2017\/BMD-3684 MOIR2-CM"]}]},{"name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades of Spain","award":["S2022\/BMD-7227 MOIR-ACTOME-CM"],"award-info":[{"award-number":["S2022\/BMD-7227 MOIR-ACTOME-CM"]}]},{"name":"Comunidad de Madrid","award":["RTI2018-095615-B-I00"],"award-info":[{"award-number":["RTI2018-095615-B-I00"]}]},{"name":"Comunidad de Madrid","award":["PID2021-123865OB-I00"],"award-info":[{"award-number":["PID2021-123865OB-I00"]}]},{"name":"Comunidad de Madrid","award":["S2017\/BMD-3684 MOIR2-CM"],"award-info":[{"award-number":["S2017\/BMD-3684 MOIR2-CM"]}]},{"name":"Comunidad de Madrid","award":["S2022\/BMD-7227 MOIR-ACTOME-CM"],"award-info":[{"award-number":["S2022\/BMD-7227 MOIR-ACTOME-CM"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pleiotrophin (PTN) is crucial for embryonic development and pancreas organogenesis as it regulates metainflammation, metabolic homeostasis, thermogenesis, and glucose tolerance. Pleiotrophin deletion is associated with a lipodystrophic phenotype in which adipose tissue plasticity is altered in late life. This study explored the impact of pleiotrophin deletion on pancreatic morphology and function in later life. We analyzed glucose tolerance and circulating parameters on female wild-type (Ptn+\/+) and knock-out (Ptn\u2212\/\u2212) mice. At 9 and 15 months, we conducted morphometric analyses of pancreatic islets and evaluated the levels of insulin, glucagon, somatostatin, glucose transporter 2 (GLUT2), vesicle-associated membrane protein 2 (VAMP2), and synaptosome-associated protein 25 (SNAP25) via immunofluorescence. The effect of PTN on glucose-stimulated insulin secretion (GSIS) was evaluated in INS1E cells and isolated islets. Ptn\u2212\/\u2212 mice showed hyperinsulinemia, impaired glucose tolerance, and increased homeostatic model assessment for insulin resistance (HOMA-IR) with age. While Ptn+\/+ islets enlarge with age, in Ptn\u2212\/\u2212 mice, the median size decreased, and insulin content increased. Vesicle transport and exocytosis proteins were significantly increased in 9-month-old Ptn\u2212\/\u2212 islets. Islets from Ptn\u2212\/\u2212 mice showed impaired GSIS and decreased cell membrane localization of GLUT2 whereas, PTN increased GSIS in INS1E cells. Ptn deletion accelerated age-related changes in the endocrine pancreas, affecting islet number and size, and altering VAMP2 and SNAP25 levels and GLUT2 localization leading to impaired GSIS and insulin accumulation in islets.<\/jats:p>","DOI":"10.3390\/ijms252010960","type":"journal-article","created":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T08:54:27Z","timestamp":1728636867000},"page":"10960","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Constitutive Pleiotrophin Deletion Results in a Phenotype with an Altered Pancreatic Morphology and Function in Old Mice"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8656-9171","authenticated-orcid":false,"given":"Cristina","family":"Ballesteros-Pla","sequence":"first","affiliation":[{"name":"Departamento de Qu\u00edmica y Bioqu\u00edmica, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanizaci\u00f3n Montepr\u00edncipe, Boadilla del Monte, 28660 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7726-6673","authenticated-orcid":false,"given":"Julio","family":"Sevillano","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica y Bioqu\u00edmica, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanizaci\u00f3n Montepr\u00edncipe, Boadilla del Monte, 28660 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7788-8923","authenticated-orcid":false,"given":"Mar\u00eda Gracia","family":"S\u00e1nchez-Alonso","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica y Bioqu\u00edmica, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanizaci\u00f3n Montepr\u00edncipe, Boadilla del Monte, 28660 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6064-2855","authenticated-orcid":false,"given":"Mar\u00eda","family":"Limones","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica y Bioqu\u00edmica, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanizaci\u00f3n Montepr\u00edncipe, Boadilla del Monte, 28660 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimena","family":"Pita","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica y Bioqu\u00edmica, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanizaci\u00f3n Montepr\u00edncipe, Boadilla del Monte, 28660 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6073-6181","authenticated-orcid":false,"given":"Bego\u00f1a","family":"Zapater\u00eda","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica y Bioqu\u00edmica, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanizaci\u00f3n Montepr\u00edncipe, Boadilla del Monte, 28660 Madrid, Spain"},{"name":"Department of Medicine, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6898-7660","authenticated-orcid":false,"given":"Marta Inmaculada","family":"Sanz-Cuadrado","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica y Bioqu\u00edmica, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanizaci\u00f3n Montepr\u00edncipe, Boadilla del Monte, 28660 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Pizarro-Delgado","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica y Bioqu\u00edmica, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanizaci\u00f3n Montepr\u00edncipe, Boadilla del Monte, 28660 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6920-4939","authenticated-orcid":false,"given":"Adriana","family":"Izquierdo-Lahuerta","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias B\u00e1sicas de la Salud, Universidad Rey Juan Carlos, Alcorc\u00f3n, 28922 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8169-681X","authenticated-orcid":false,"given":"Gema","family":"Medina-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias B\u00e1sicas de la Salud, Universidad Rey Juan Carlos, Alcorc\u00f3n, 28922 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gonzalo","family":"Herrad\u00f3n","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Farmac\u00e9uticas y de la Salud, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Boadilla del Monte Urbanizaci\u00f3n Montepr\u00edncipe, 28660 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7727-7783","authenticated-orcid":false,"given":"Mar\u00eda del Pilar","family":"Ramos-\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica y Bioqu\u00edmica, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanizaci\u00f3n Montepr\u00edncipe, Boadilla del Monte, 28660 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/0006-291X(90)90753-A","article-title":"Heparin-binding neurotrophic factor (HBNF) and MK, members of a new family of homologous, developmentally regulated 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