{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T05:29:10Z","timestamp":1793338150325,"version":"4.5.0"},"reference-count":35,"publisher":"National Academy of Sciences","issue":"14","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,4,7]]},"abstract":"<jats:p>\n                    Altered growth and development of the endocrine pancreas is a frequent cause of the hyperglycemia associated with diabetes. Here we show that microRNA-375 (\n                    <jats:italic>miR-375<\/jats:italic>\n                    ), which is highly expressed in pancreatic islets, is required for normal glucose homeostasis. Mice lacking\n                    <jats:italic>miR-375<\/jats:italic>\n                    (\n                    <jats:italic>375KO<\/jats:italic>\n                    ) are hyperglycemic, exhibit increased total pancreatic \u03b1-cell numbers, fasting and fed plasma glucagon levels, and increased gluconeogenesis and hepatic glucose output. Furthermore, pancreatic \u03b2-cell mass is decreased in\n                    <jats:italic>375KO<\/jats:italic>\n                    mice as a result of impaired proliferation. In contrast, pancreatic islets of obese mice (\n                    <jats:italic>ob<\/jats:italic>\n                    \/\n                    <jats:italic>ob<\/jats:italic>\n                    ), a model of increased \u03b2-cell mass, exhibit increased expression of\n                    <jats:italic>miR-375<\/jats:italic>\n                    . Genetic deletion of\n                    <jats:italic>miR-375<\/jats:italic>\n                    from these animals (\n                    <jats:italic>375<\/jats:italic>\n                    \/\n                    <jats:italic>ob<\/jats:italic>\n                    ) profoundly diminished the proliferative capacity of the endocrine pancreas and resulted in a severely diabetic state. Bioinformatic analysis of transcript data from\n                    <jats:italic>375KO<\/jats:italic>\n                    islets revealed that\n                    <jats:italic>miR-375<\/jats:italic>\n                    regulates a cluster of genes controlling cellular growth and proliferation. These data provide evidence that\n                    <jats:italic>miR-375<\/jats:italic>\n                    is essential for normal glucose homeostasis, \u03b1- and \u03b2-cell turnover, and adaptive \u03b2-cell expansion in response to increasing insulin demand in insulin resistance.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0810550106","type":"journal-article","created":{"date-parts":[[2009,3,16]],"date-time":"2009-03-16T21:38:29Z","timestamp":1237239509000},"page":"5813-5818","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":690,"title":["<i>miR-375<\/i>\n                    maintains normal pancreatic \u03b1- and \u03b2-cell mass"],"prefix":"10.1073","volume":"106","author":[{"given":"Matthew N.","family":"Poy","sequence":"first","affiliation":[{"name":"Institute of Molecular Systems Biology, Swiss Federal Institute of Technology, ETH Zurich, CH-8093 Zurich, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Hausser","sequence":"additional","affiliation":[{"name":"Swiss Institute of Bioinformatics, Biozentrum, University of Basel, 4056 Basel, Switzerland; 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