{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T11:55:00Z","timestamp":1761738900710,"version":"build-2065373602"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Pancreatic \u03b2-cell dysfunction is a key contributor to the development of Type 2 Diabetes. The platelet-derived growth factor receptor \u03b1 (PDGFR\u03b1) is known to play a crucial role in \u03b2-cell proliferation and expansion. However, its specific role in \u03b2-cell function and glucose metabolism remains unclear. This study aimed to investigate the effects of Pdgfr\u03b1 deficiency on islet \u03b2-cell function and overall glucose metabolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To explore this, we generated \u03b2-cell-specific Pdgfr\u03b1-deficient C57BL\/6 mice (Pdgfra\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      Pdx1-cre\n                      <jats:sup>+<\/jats:sup>\n                      ) and assessed their metabolic function under both normal and high-fat diet conditions. Various parameters were measured, including body weight, body fat composition, glucose metabolism, insulin content, and \u03b2-cell apoptosis. Additionally, we conducted mechanistic analyses to understand the signaling pathways involved.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Pdgfr\u03b1-deficient mice exhibited significantly greater weight gain and increased body fat compared to controls. These mice also showed impaired glucose metabolism, reduced insulin content in \u03b2-cells, and increased \u03b2-cell apoptosis. Mechanistic studies revealed that Pdgfr\u03b1 deletion led to suppression of Atf5 expression via downregulation of the PI3K pathway. This suppression resulted in enhanced \u03b2-cell apoptosis. Furthermore, Atf5 was found to regulate the expression of Gadd45b, Bcl2, and aminoacyl-tRNA synthetases, which are involved in insulin biosynthesis and glucose metabolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our findings demonstrate that PDGFR\u03b1 plays a critical role in maintaining \u03b2-cell function and glucose homeostasis. Loss of PDGFR\u03b1 impairs \u03b2-cell survival and insulin production, likely through the PI3K\u2013Atf5 axis. These insights suggest that targeting \u03b2-cell apoptotic pathways, particularly involving Atf5 and its downstream effectors, may offer promising avenues for the prevention and treatment of Type 2 Diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2025.1630979","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T05:30:49Z","timestamp":1761715849000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pdgfr\u03b1 deficiency in islet \u03b2-cells up-regulates apoptosis of beta-cells and disturbs glucose metabolism in B6 mice"],"prefix":"10.3389","volume":"16","author":[{"given":"Luyao","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanpeng","family":"Xing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianlei","family":"Gu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James Alexander","family":"Pearson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youjia","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F. 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