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MicroRNA-214 Suppresses Gluconeogenesis by Targeting Activating Transcriptional Factor 4.
- Source :
-
Journal of Biological Chemistry . 3/27/2015, Vol. 290 Issue 13, p8185-8195. 11p. - Publication Year :
- 2015
-
Abstract
- Although the gluconeogenesis pathway is already a target for the treatment of type 2 diabetes, the potential role of micro- RNAs (miRNAs) in gluconeogenesis remains unclear. Here, we investigated the physiological functions of miR-214 in gluconeogenesis. The expression of miR-214 was suppressed by glucagon via protein kinaseAsignaling in primary hepatocytes, and miR-214 was down-regulated in the livers of fasted, high fat dietinduced diabetic and leptin receptor-mutated (db/db) mice. The overexpression of miR-214 in primary hepatocytes suppressed glucose production, and silencing miR-214 reversed this effect. Gluconeogenesis was suppressed in the livers of mice injected with an adenovirus expressing miR-214 (Ad-miR-214). Additionally, Ad-miR-214 alleviated high fat diet-induced elevation of gluconeogenesis and hyperglycemia. Furthermore, we found that activating transcription factor 4 (ATF4), a reported target of miR-214, can reverse the suppressive effect of miR-214 on gluconeogenesis in primary hepatocytes, and this suppressive effect was blocked in liver-specific ATF4 knock-out mice. ATF4 regulated gluconeogenesis via affecting forkhead box protein O1(FOXO1) transcriptional activity. Finally, liver-specific miR- 214 transgenic mice exhibited suppressed gluconeogenesis and reduced expression of ATF4, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase in liver. Taken together, our results suggest that the miR-214-ATF4 axis is a novel pathway for the regulation of hepatic gluconeogenesis. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00219258
- Volume :
- 290
- Issue :
- 13
- Database :
- Academic Search Index
- Journal :
- Journal of Biological Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 101878208
- Full Text :
- https://doi.org/10.1074/jbc.M114.633990