{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T17:13:01Z","timestamp":1789146781472,"version":"build-2803163510"},"reference-count":32,"publisher":"The Company of Biologists","issue":"18","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-2\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"crossref","award":["24K02501"],"award-info":[{"award-number":["24K02501"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"crossref","award":["20K08325"],"award-info":[{"award-number":["20K08325"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004014","name":"Japan IDDM Network","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004014","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Vesicular monoamine transporter 2 (VMAT2) transports monoamines into storage vesicles. We have previously reported that VMAT2 negatively regulates pancreatic progenitor differentiation into endocrine beta cells; however, the underlying mechanism remains unknown. Using a pancreatic bud explant culture, we show here that inhibiting VMAT2-mediated catecholamine uptake promotes pancreatic epithelial branching and increases the number of insulin-expressing cells. The increase in pancreatic branching was mimicked by inhibition of tyrosine hydroxylase, monoamine oxidase A, dopamine beta-hydroxylase or norepinephrine transporter. RNA sequencing analysis of the pancreatic buds revealed that reactive oxygen species (ROS) play a role in branch formation. We found that these early glucagon (GCG) and insulin (INS) co-expressing cells express VMAT2 and monoamine signaling components. Lineage-specific VMAT2 deletion in Gcg-expressing cells resulted in increased pancreatic branching and islet areas, and decreased ROS accumulation. We conclude that early GCG and INS co-expressing cells regulate pancreatic branching morphogenesis via VMAT2\u2013noradrenaline-mediated ROS signaling.<\/jats:p>","DOI":"10.1242\/dev.205734","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:54:31Z","timestamp":1787730871000},"source":"Crossref","is-referenced-by-count":0,"title":["Early glucagon-positive cells restrict pancreatic branching through VMAT2\u2013noradrenaline-mediated ROS signaling"],"prefix":"10.1242","volume":"153","author":[{"given":"Airi","family":"Inoue","sequence":"first","affiliation":[{"name":"School of Life Science and Technology, Institute of Science Tokyo , 4259-B-25 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-8501 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0699-1768","authenticated-orcid":false,"given":"Fumiya","family":"Uefune","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology, Institute of Science Tokyo , 4259-B-25 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-8501 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Shitamichi","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology, Institute of Science Tokyo , 4259-B-25 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-8501 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5305-5556","authenticated-orcid":false,"given":"Daisuke","family":"Sakano","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology, Institute of Science Tokyo , 4259-B-25 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-8501 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4292-205X","authenticated-orcid":false,"given":"Shoen","family":"Kume","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology, Institute of Science Tokyo , 4259-B-25 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-8501 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"2026091112464033500_DEV205734C1","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1111\/j.1476-5381.2012.01975.x","article-title":"The solute carrier 6 family of transporters","volume":"167","author":"Br\u00f6er","year":"2012","journal-title":"Br. 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