title: MicroRNA 152 regulates hepatic glycogenesis by targeting PTEN.
abstract: Hepatic insulin resistance, defined as a diminished ability of hepatocytes to respond to the action of insulin, plays an important role in the development of type 2 diabetes and metabolic syndrome. Aberrant expression of mmu-miR-152-3p (miR-152) is related to the pathogenesis of tumors such as hepatitis B virus related hepatocellular carcinoma. However, the role of miR-152 in hepatic insulin resistance remains unknown. In the present study, we identified the potential role of miR-152 in regulating hepatic glycogenesis. The expression of miR-152 and the level of glycogen were significantly downregulated in the liver of db/db mice and mice fed a high fat diet. In vivo and in vitro results suggest that inhibition of miR-152 expression induced impaired glycogenesis in hepatocytes. Interestingly, miR-152 expression, glycogen synthesis and protein kinase B/glycogen synthase kinase (AKT/GSK) pathway activation were significantly decreased in the liver of mice injected with 16 μg·mL(-1) interleukin 6 (IL-6) by pumps for 7 days and in NCTC 1469 cells treated with 10 ng·mL(-1) IL-6 for 24 h. Moreover, hepatic overexpression of miR-152 rescued IL-6-induced impaired glycogenesis. Finally, phosphatase and tensin homolog (PTEN) was identified as a direct target of miR-152 to mediate hepatic glycogen synthesis. Our findings provide mechanistic insight into the effects of miR-152 on the regulation of the AKT/GSK pathway and the synthesis of glycogen in hepatocytes. Downregulated miR-152 induced impaired hepatic glycogenesis by targeting PTEN. PTEN participated in miR-152-mediated glycogenesis in hepatocytes via regulation of the AKT/GSK pathway.
authors.affiliation: Peking University Fifth School of Clinical Medicine, Beijing, China.
authors.forename: Shuyue
authors.initials: S
authors.lastname: Wang
authors.affiliation: Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, China.|Department of Medicine, Shenzhen Family Planning Service Center, Guangdong, China.
authors.forename: Lilin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Dou
authors.affiliation: Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.affiliation: Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Fang
authors.affiliation: Peking University Fifth School of Clinical Medicine, Beijing, China.|Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: Peking University Fifth School of Clinical Medicine, Beijing, China.|Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Meng
authors.affiliation: Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Man
authors.affiliation: Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Shen
authors.affiliation: Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, China.
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Huang
authors.affiliation: Peking University Fifth School of Clinical Medicine, Beijing, China.|Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D059305:Diet, High-Fat; D015850:Interleukin-6 / Q000008:administration & dosage; D008112:Liver Glycogen / Q000096:biosynthesis*; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; D008112:Liver Glycogen; C550857:MIRN152 microRNA, mouse; D035683:MicroRNAs; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse
keywords: IL-6; glycogenesis; insulin signal pathway; microRNA 152