{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T10:38:53Z","timestamp":1783593533603,"version":"3.55.0"},"reference-count":83,"publisher":"National Academy of Sciences","issue":"33","license":[{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["DK132090"],"award-info":[{"award-number":["DK132090"]}]},{"name":"NIH","award":["DK020579"],"award-info":[{"award-number":["DK020579"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,8,13]]},"abstract":"<jats:p>\n                    Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER)-resident secretory protein that reduces inflammation and promotes proliferation in pancreatic \u03b2 cells. Numerous studies have highlighted the potential of MANF as a therapeutic agent for diabetes mellitus (DM), making it essential to understand the mechanisms underlying MANF\u2019s functions. In our previous search for a molecule that mediates MANF signaling, we identified Neuroplastin (NPTN) as a binding partner of MANF that localizes on the cell surface. However, the roles of NPTN in pancreatic \u03b2 cells remain unclear. In this study, we generated \u03b2 cell\u2013specific\n                    <jats:italic>Nptn<\/jats:italic>\n                    knockout (KO) mice and conducted metabolic characterization. NPTN deficiency improved glucose tolerance by increasing insulin secretion and \u03b2 cell mass in the pancreas. Moreover, proliferation and mitochondrial numbers in \u03b2 cells increased in\n                    <jats:italic>Nptn<\/jats:italic>\n                    KO islets. These phenotypes resulted from elevated cytosolic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    levels and subsequent activation of downstream molecules. Simultaneously, we demonstrated that NPTN induces the expression of proinflammatory cytokines via the TRAF6\u2013NF-\u03baB axis in \u03b2 cells. Additionally, NPTN deficiency conferred resistance to streptozotocin-induced diabetic phenotypes. Finally, exogenous MANF treatment in islets or \u03b2 cells led to similar phenotypes as those observed in NPTN-deficient models. These results indicate that NPTN plays important roles in the regulation of insulin secretion, proliferation, and mitochondrial quantity, as well as proinflammatory responses, which are antagonized by MANF treatment. Thus, targeting the MANF\u2013NPTN interaction may lead to a novel treatment for improving \u03b2 cell functions in DM.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2411234121","type":"journal-article","created":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T13:45:07Z","timestamp":1722951907000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":6,"title":["Dual role of neuroplastin in pancreatic \u03b2 cells: Regulating insulin secretion and promoting islet inflammation"],"prefix":"10.1073","volume":"121","author":[{"given":"Rie Asada","family":"Kitamura","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, MO 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A. Kitamura D. Hummel A. Ustione D. W. Piston F. Urano Dual role of neuroplastin in pancreatic \u03b2 cells: Regulating insulin secretion and promoting islet inflammation. GEO. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE272736. 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