{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T21:52:37Z","timestamp":1790200357235,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2018,11,9]],"date-time":"2018-11-09T00:00:00Z","timestamp":1541721600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2017R1A6A3A01004397, 2018R1A2B2005219, and 2018R1D1A1B07046882"],"award-info":[{"award-number":["2017R1A6A3A01004397, 2018R1A2B2005219, and 2018R1D1A1B07046882"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Type 2 diabetes mellitus (T2DM) is a chronic disease manifested by hyperglycemia. It is essential to effectively control hyperglycemia to prevent complications of T2DM. Here, we hypothesize that repression of transcriptional activity of forkhead box O1 (FoxO1) via histone deacetylase inhibitors (HDACi) ameliorates hyperglycemia in T2DM rats. Methods: Male Long-Evans Tokushima Otsuka (LETO) and Otsuka Long-Evans Tokushima Fatty (OLETF) rats aged 14 weeks were administered sodium valproate (VPA, 0.71% w\/v) dissolved in water for 20 weeks. Electrophoretic mobility shift assay (EMSA) and luciferase assay were performed for elucidation of transcriptional regulation through acetylation of FoxO1 by HDACi. Results: VPA attenuated blood glucose levels in accordance with a decrease in the expression of gluconeogenic genes in hyperglycemic OLETF rats. It has been shown that HDAC class I-specific and HDAC class IIa-specific inhibitors, as well as pan-HDAC inhibitors decrease FoxO1 enrichment at the cis-element of target gene promoters. Mutations in FoxO1 prevent its acetylation, thereby increasing its transcriptional activity. HDAC3 and HDAC4 interact with FoxO1, and knockdown of HDAC3, HDAC4, or their combination increases FoxO1 acetylation, thereby decreasing the expression of gluconeogenic genes. Conclusions: These results indicate that HDACi attenuates the transcriptional activity of FoxO1 by impeding deacetylation, thereby ameliorating hyperglycemia in T2DM rats.<\/jats:p>","DOI":"10.3390\/ijms19113539","type":"journal-article","created":{"date-parts":[[2018,11,13]],"date-time":"2018-11-13T03:27:31Z","timestamp":1542079651000},"page":"3539","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Repression of Transcriptional Activity of Forkhead Box O1 by Histone Deacetylase Inhibitors Ameliorates Hyperglycemia in Type 2 Diabetic Rats"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6534-1752","authenticated-orcid":false,"given":"Hyun Min","family":"Cho","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 41944, Korea"},{"name":"Cardiovascular Research Institute, School of Medicine, Kyungpook National University, Daegu 41944, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1273-3861","authenticated-orcid":false,"given":"Young Mi","family":"Seok","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, School of Medicine, Kyungpook National University, Daegu 41944, Korea"},{"name":"National Development Institute of Korean Medicine, Gyeongsan, Gyeongbuk 38540, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hae Ahm","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 41944, Korea"},{"name":"Department of Medical Zoology, Kyung Hee University School of Medicine, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minji","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 41944, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8009-5801","authenticated-orcid":false,"given":"InKyeom","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 41944, Korea"},{"name":"Cardiovascular Research Institute, School of Medicine, Kyungpook National University, Daegu 41944, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.diabres.2012.11.006","article-title":"By the Numbers: New Estimates from the Idf Diabetes Atlas Update for 2012","volume":"98","author":"Guariguata","year":"2012","journal-title":"Diabetes Res. 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