title: MicroRNA-29a-c decrease fasting blood glucose levels by negatively regulating hepatic gluconeogenesis.
abstract: OBJECTIVE
  The expression levels of microRNA-29 (miR-29) family members (miR-29a, miR-29b, miR-29c, here denoted collectively as miR-29a-c) are increased in livers of Goto-Kakizaki diabetic rats and db/db diabetic mice. However, the functional consequences of miR-29a-c upregulation in diabetic livers are not explored. The objective of this study was to evaluate the roles of miR-29a-c in the regulation of hepatic glucose production and blood glucose levels using different mouse models.
  
  
  METHODS
  db/m, db/db diabetic and diet-induced obese (DIO) mice were injected with adenovirus expressing miR-29a-c through the tail vein. Blood glucose levels were measured and glucose-tolerance tests and pyruvate-tolerance tests were performed. To explore the molecular mechanism by which miR-29a-c regulate hepatic glucose metabolism, gain or loss of miR-29a-c function studies were performed in primary mouse hepatocytes and the direct effectors of miR-29-mediated effects on glucose metabolism were identified.
  
  
  RESULTS
  Adenovirus-mediated overexpression of miR-29a-c in the livers of db/m, db/db, and DIO mice decreased fasting blood glucose levels and improved glucose tolerance. Overexpression of miR-29a-c in primary hepatocytes and mouse livers decreased the protein levels of PGC-1α and G6Pase, the direct targets of miR-29a-c, thereby reducing cellular, and hepatic glucose production. In contrast, loss of miR-29a-c function in primary hepatocytes increased the protein levels of PGC-1α and G6Pase and increased cellular glucose production. Finally, enforced expression of PGC-1α increased miR-29a-c expression levels in primary hepatocytes, thus forming a negative feedback regulation loop.
  
  
  CONCLUSIONS
  miR-29a-c can regulate hepatic glucose production and glucose tolerance in mice.
authors.affiliation: Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, Hubei University, Wuhan 430062, China.
authors.forename: Jichao
authors.initials: J
authors.lastname: Liang
authors.forename: Changzheng
authors.initials: C
authors.lastname: Liu
authors.forename: Aijun
authors.initials: A
authors.lastname: Qiao
authors.forename: Ying
authors.initials: Y
authors.lastname: Cui
authors.forename: Huabing
authors.initials: H
authors.lastname: Zhang
authors.forename: Anfang
authors.initials: A
authors.lastname: Cui
authors.forename: Shutian
authors.initials: S
authors.lastname: Zhang
authors.forename: Yanli
authors.initials: Y
authors.lastname: Yang
authors.forename: Xinhua
authors.initials: X
authors.lastname: Xiao
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.forename: Fude
authors.initials: F
authors.lastname: Fang
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Chang
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis*; D005576:Colforsin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005215:Fasting / Q000378:metabolism*; D005943:Gluconeogenesis; D005952:Glucose-6-Phosphatase / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000502:physiology*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D051381:Rats; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors
chemical_list: D001786:Blood Glucose; C547014:MIRN29 microRNA, mouse; C526366:MIRN29 microRNA, rat; D035683:MicroRNAs; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D005576:Colforsin; D003907:Dexamethasone; D005952:Glucose-6-Phosphatase