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Micro-RNAs (miRNAs) have been identified as critical regulators of diabetes and other metabolic disorders. In this study, we found that the expressions of miRNA-27 family members miRNA-27a and miRNA-27b (miR-27a\/b) decreased significantly in the livers of diabetic mice. Moreover, the levels of miR-27a\/b increased in the serum of patients with type 2 diabetes. Our present results showed that inhibition of miR-27a\/b expression led to increased hepatic protein levels of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase and enhanced hepatic gluconeogenesis in vitro and in vivo. Overexpression of miR-27a\/b suppressed hepatic glucose output and alleviated hyperglycemia in diabetic mice. Further study revealed that forkhead box O1 (FOXO1) is a downstream target of miR-27a\/b. Taken together, we found novel evidence suggesting that miR-27a\/b contributes to hepatic gluconeogenesis through targeting FOXO1 and provided novel mechanistic insight into the pathophysiology of insulin resistance. <\/jats:p>","DOI":"10.1152\/ajpendo.00190.2019","type":"journal-article","created":{"date-parts":[[2019,9,17]],"date-time":"2019-09-17T16:38:13Z","timestamp":1568738293000},"page":"E911-E924","source":"Crossref","is-referenced-by-count":29,"title":["Micro-RNA-27a\/b negatively regulates hepatic gluconeogenesis by targeting FOXO1"],"prefix":"10.1152","volume":"317","author":[{"given":"Shuyue","family":"Wang","sequence":"first","affiliation":[{"name":"National Engineering Laboratory for Druggable Gene and Protein Screening, School of Life Sciences, Northeast Normal University, Changchun, China"},{"name":"Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education, Northeast Normal University, Changchun, 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