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MicroRNA 152 regulates hepatic glycogenesis by targeting PTEN

Wang, Shuyue, Wang, Lilin, Dou, Lin, Guo, Jun, Fang, Weiwei, Li, Meng, Meng, Xiangyu, Man, Yong, Shen, Tao, Huang, Xiuqing, Li, Jian
The FEBS journal 2016 v.283 no.10 pp. 1935-1946
Hepatitis B virus, glycogen, glycogen synthase kinases, glycogenesis, hepatocytes, hepatoma, high fat diet, insulin, insulin resistance, interleukin-6, liver, metabolic syndrome, mice, microRNA, non-specific serine/threonine protein kinase, noninsulin-dependent diabetes mellitus, pathogenesis, pumps
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.