{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T15:56:12Z","timestamp":1765209372445,"version":"3.46.0"},"reference-count":20,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Veterinary Sciences"],"abstract":"<jats:p>Transcription factors control the development of the endocrine pancreas in various mammals. In humans, paired box-4 (PAX4) and aristaless-related homeobox (ARX) allocate endocrine progenitor cells toward \u03b2-cell and \u03b1-cell specification, respectively. In adulthood, PAX4 contributes to reprogramming \u03b1-cells into \u03b2-cells and exocrine into endocrine cells; induction of ARX in \u03b2-cells drives them to reprogram into \u03b1-cells. Feline diabetes mellitus has a similar pathophysiology to human type 2 diabetes, but information about the role of these transcription factors is unavailable in diabetic cats. The study aim was to test whether diabetic cats have an increased number of pancreatic cells expressing developmental markers of \u03b2- and \u03b1-cells, respectively, suggesting reprogramming. In 9 diabetic and 9 well-matched control cats, pancreas was collected, formalin-fixed and paraffin-embedded. Tissue slides were labelled for insulin, glucagon, PAX4, and ARX. Positive cells for each marker and double-positive cells for their combinations were counted in the pancreas and compared between groups. Against controls, diabetic cats had fewer insulin-positive cells in the islets (p = 0.001) and exocrine pancreas (p = 0.038); glucagon-positive cells were similar. In the islets, diabetic cats had higher counts of insulin\/glucagon-positive cells (p = 0.024), PAX4-positive cells (p = 0.038), as well as PAX4\/insulin-positive cells (p = 0.027). In conclusion, in diabetic cats, the increased number of islet cells expressing PAX4 leads to the hypothesis that \u03b2-cells change to an earlier stage of differentiation or that novel \u03b2-cells are formed. Furthermore, the higher count of islet insulin\/glucagon-positive cells might indicate that \u03b1-cells transform into \u03b2-cells or vice versa. Hence, reprogramming seems possible in diabetic cats, specifically in the islets.<\/jats:p>","DOI":"10.3390\/vetsci12121167","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T14:52:24Z","timestamp":1765205544000},"page":"1167","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of Pancreatic Endocrine Reprogramming in Diabetic Cats"],"prefix":"10.3390","volume":"12","author":[{"given":"Lune D.","family":"Geurts","sequence":"first","affiliation":[{"name":"AniCura Dierenkliniek Rijngeest, President Kennedylaan 260, 2343 GX Oegstgeest, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Zanon","sequence":"additional","affiliation":[{"name":"Department of Animal Medicine, Production and Health, University of Padova, viale dell\u2019Universit\u00e0 16, 35020 Legnaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7054-5116","authenticated-orcid":false,"given":"Eylem E.","family":"Akyurek","sequence":"additional","affiliation":[{"name":"Department of Comparative Biomedicine and Food Sciences, University of Padova, viale dell\u2019Universit\u00e0 16, 35020 Legnaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3643-7568","authenticated-orcid":false,"given":"Silvia","family":"Ferro","sequence":"additional","affiliation":[{"name":"Department of Comparative Biomedicine and Food Sciences, University of Padova, viale dell\u2019Universit\u00e0 16, 35020 Legnaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8884-8302","authenticated-orcid":false,"given":"Roberta","family":"Sacchetto","sequence":"additional","affiliation":[{"name":"Department of Comparative Biomedicine and Food Sciences, University of Padova, viale dell\u2019Universit\u00e0 16, 35020 Legnaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mila Della","family":"Barbera","sequence":"additional","affiliation":[{"name":"Department of Cardiac, Thoracic and Vascular Science, Cardiovascular Pathology Section, University of Padova, via A. Gabelli 61, 35121 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"Callegari","sequence":"additional","affiliation":[{"name":"IDEXX Laboratories Italia, via Guglielmo Silva 36, 20149 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9423-614X","authenticated-orcid":false,"given":"Gabriele","family":"Gerardi","sequence":"additional","affiliation":[{"name":"Department of Animal Medicine, Production and Health, University of Padova, viale dell\u2019Universit\u00e0 16, 35020 Legnaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3121-2199","authenticated-orcid":false,"given":"Federico","family":"Fracassi","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medical Science, University of Bologna, via Tolara di Sopra 43, 40064 Ozzano dell\u2019Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8058-0492","authenticated-orcid":false,"given":"Hans S.","family":"Kooistra","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, 3584 CM Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas A.","family":"Lutz","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, 8057 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Zini","sequence":"additional","affiliation":[{"name":"Department of Animal Medicine, Production and Health, University of Padova, viale dell\u2019Universit\u00e0 16, 35020 Legnaro, Italy"},{"name":"Clinic for Small Animal Internal Medicine, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, 8057 Zurich, Switzerland"},{"name":"AniCura Istituto Veterinario Novara, Strada Provinciale 9, 28060 Granozzo con Monticello, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2591","DOI":"10.1101\/gad.269003","article-title":"Opposing actions of ARX and PAX4 in endocrine pancreas development","volume":"17","author":"Collombat","year":"2003","journal-title":"Genes Dev."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Bonnavion, R., Jaafar, R., Kerr-Conte, J., Assade, F., van Stralen, E., Leteurtre, E., Pouponnot, C., Gargani, S., Pattou, F., and Bertolino, P. 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