{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T04:29:22Z","timestamp":1792297762778,"version":"4.4.0"},"reference-count":58,"publisher":"American Diabetes Association","issue":"5","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/100017618","name":"Division of Diabetes, Endocrinology, and Metabolic Diseases","doi-asserted-by":"publisher","award":["1R21DK129968-01 (SB)"],"award-info":[{"award-number":["1R21DK129968-01 (SB)"]}],"id":[{"id":"10.13039\/100017618","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017618","name":"Division of Diabetes, Endocrinology, and Metabolic Diseases","doi-asserted-by":"publisher","award":["Diabetes Research Center (DRC) Grant P30DK079626-1"],"award-info":[{"award-number":["Diabetes Research Center (DRC) Grant P30DK079626-1"]}],"id":[{"id":"10.13039\/100017618","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017618","name":"Division of Diabetes, Endocrinology, and Metabolic Diseases","doi-asserted-by":"publisher","award":["R00 DK95975-03 (SB)"],"award-info":[{"award-number":["R00 DK95975-03 (SB)"]}],"id":[{"id":"10.13039\/100017618","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017618","name":"Division of Diabetes, Endocrinology, and Metabolic Diseases","doi-asserted-by":"publisher","award":["R01 DK128132 (CSH), R01 DK111483 (CSH)"],"award-info":[{"award-number":["R01 DK128132 (CSH), R01 DK111483 (CSH)"]}],"id":[{"id":"10.13039\/100017618","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017618","name":"Division of Diabetes, Endocrinology, and Metabolic Diseases","doi-asserted-by":"publisher","award":["R01DK120684 (SB)"],"award-info":[{"award-number":["R01DK120684 (SB)"]}],"id":[{"id":"10.13039\/100017618","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,5,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>The transition from a proliferative to a functionally mature state is a critical phase in postnatal pancreatic \u03b2-cell development, yet the molecular mechanisms coordinating this shift remain poorly understood. Here, we identify tomosyn-2 as a key regulator that restrains \u03b2-cell maturation and insulin secretory capacity. Tomosyn-2 expression progressively declines in mouse islets with age, coinciding with enhanced biphasic glucose-stimulated insulin secretion and reduced \u03b2-cell proliferation. Mice lacking tomosyn-2 exhibit improved glucose clearance, elevated plasma insulin levels, and enhanced insulin secretion from isolated islets without changes in insulin action. Mechanistically, tomosyn-2 interacts with syntaxin-1A to inhibit insulin granule exocytosis by limiting SNARE complex assembly. Transcriptomic and network analyses reveal that loss of tomosyn-2 is associated with coordinated changes in insulin secretion and cell-cycle regulation, reducing \u03b2-cell proliferation and mass expansion by downregulating Akt1 signaling and cell-cycle mediators, while promoting \u03b2-cell identity and functional maturation accompanied by altered islet cytoarchitecture. These findings identify tomosyn-2 as a molecular brake that balances proliferation and insulin secretion to achieve a threshold of functionally mature \u03b2-cell mass during postnatal development. Targeting tomosyn-2 or its downstream pathways may enhance \u03b2-cell functional competence and offer new strategies to restore insulin secretion in diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                    <jats:p>The mechanisms governing the postnatal transition of pancreatic \u03b2-cells from a proliferative, immature state to a functionally mature, glucose-responsive state remain poorly understood. We investigate the role of tomosyn-2 in modulating \u03b2-cell proliferation and insulin secretion during postnatal maturation. Tomosyn-2 inhibits SNARE complex formation and insulin secretion, and its loss is associated with enhanced \u03b2-cell maturation, increased biphasic insulin secretion, reduced \u03b2-cell proliferation, and suppressed Akt1-cyclinD1 signaling. Tomosyn-2 functions as a physiological brake on insulin secretion, coordinating the balance between \u03b2-cell maturation and proliferation, with implications for diabetes pathogenesis and \u03b2-cell regenerative strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db25-0644","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T19:01:41Z","timestamp":1776711701000},"page":"799-815","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":1,"title":["Tomosyn-2 Regulates Postnatal \u03b2-Cell Expansion and Insulin Secretion to Maintain Glucose Homeostasis"],"prefix":"10.2337","volume":"75","author":[{"given":"Katherine C.","family":"Perez","sequence":"first","affiliation":[{"name":"Comprehensive Diabetes Center and Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Alabama at Birmingham 1 , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Alexander","sequence":"additional","affiliation":[{"name":"Comprehensive Diabetes Center and Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Alabama at Birmingham 1 , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Mostafizur","family":"Rahman","sequence":"additional","affiliation":[{"name":"Comprehensive Diabetes Center and Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Alabama at Birmingham 1 , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haifa","family":"Alsharif","sequence":"additional","affiliation":[{"name":"Comprehensive Diabetes Center and Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Alabama at Birmingham 1 , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Liu","sequence":"additional","affiliation":[{"name":"Comprehensive Diabetes Center and Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Alabama at Birmingham 1 , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong-A","family":"Kim","sequence":"additional","affiliation":[{"name":"Comprehensive Diabetes Center and Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Alabama at Birmingham 1 , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1644-447X","authenticated-orcid":false,"given":"Chad S.","family":"Hunter","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Clinical Pharmacology, Department of Internal Medicine, University of Kansas Medical Center 2 , Kansas City, KS"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanh","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Alabama at Birmingham 3 , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2917-8588","authenticated-orcid":false,"given":"Sushant","family":"Bhatnagar","sequence":"additional","affiliation":[{"name":"Comprehensive Diabetes Center and Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Alabama at Birmingham 1 , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"2026061712322736400_B1","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/nbt.2141","article-title":"Functional beta-cell maturation is marked by an increased glucose threshold and by expression of urocortin 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