{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T15:55:02Z","timestamp":1764172502328,"version":"3.37.3"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T00:00:00Z","timestamp":1638144000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK64819"],"award-info":[{"award-number":["DK64819"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK63618"],"award-info":[{"award-number":["DK63618"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K20934"],"award-info":[{"award-number":["21K20934"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MSD Life Science foundation"},{"DOI":"10.13039\/501100005865","name":"Mochida Memorial Foundation for Medical and Pharmaceutical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008732","name":"Uehara Memorial Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008732","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Beta cell failure is a critical feature of diabetes. It includes defects of insulin production, secretion, and altered numbers of hormone-producing cells. In previous work, we have shown that beta cell failure is mechanistically linked to loss of Foxo1 function. This loss of function likely results from increased Foxo1 protein degradation, due to hyperacetylation of Foxo1 from increased nutrient turnover. To understand the mechanisms of Foxo1-related beta cell failure, we performed genome-wide analyses of its target genes, and identified putative mediators of sub-phenotypes of cellular dysfunction. Chromatin immunoprecipitation analyses demonstrated a striking pattern of Foxo1 binding to the promoters of a cluster of aldo-ketoreductases on chromosome 13: Akr1c12, Akr1c13, Akr1c19. Of these, Akr1c19 has been reported as a marker of Pdx1-positive endodermal progenitor cells. Here we show that Akr1c19 expression is dramatically decreased in <jats:italic>db\/db<\/jats:italic> islets. Thus, we investigated whether Akr1c19 is involved in beta cell function. We performed gain- and loss-of-function experiments in cultured beta cells and generated Akr1c19 knockout mice. We show that Foxo1 and HNF1a cooperatively regulate Akr1c19 expression. Nonetheless, functional characterization of Akr1c19 both using islets and knockout mice did not reveal abnormalities on glucose homeostasis. We conclude that reduced expression of Akr1c19 is not sufficient to affect islet function.<\/jats:p>","DOI":"10.1371\/journal.pone.0260526","type":"journal-article","created":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T18:26:13Z","timestamp":1638210373000},"page":"e0260526","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Aldo-ketoreductase 1c19 ablation does not affect insulin secretion in murine islets"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1487-5153","authenticated-orcid":true,"given":"Yasutaka","family":"Miyachi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taiyi","family":"Kuo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinsook","family":"Son","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Domenico","family":"Accili","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,11,29]]},"reference":[{"issue":"9","key":"pone.0260526.ref001","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.2337\/dbi18-0025","article-title":"Insulin Action Research and the Future of Diabetes Treatment: The 2017 Banting Medal for Scientific Achievement Lecture","volume":"67","author":"D Accili","year":"2018","journal-title":"Diabetes"},{"issue":"1","key":"pone.0260526.ref002","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s00125-002-1009-0","article-title":"The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes","volume":"46","author":"SE Kahn","year":"2003","journal-title":"Diabetologia"},{"issue":"27","key":"pone.0260526.ref003","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1056\/NEJM199312303292703","article-title":"Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus. 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