title: Liver-specific deletion of Ppp2cα enhances glucose metabolism and insulin sensitivity.
abstract: Protein phosphatase 2A (PP2A) is a key negative regulator of phosphatidylinositol 3-kinase/Akt pathway. Previous study showed that, in the liver, the catalytic subunit of PP2A (PP2Ac) is closely associated with insulin resistance syndrome, which is characterized by glucose intolerance and dyslipidemia. Here we studied the role of liver PP2Ac in glucose metabolism and evaluated whether PP2Ac is a suitable therapeutic target for treating insulin resistance syndrome. Liver-specific Ppp2cα knockout mice (Ppp2cα(loxp/loxp): Alb) exhibited improved glucose homeostasis compared with littermate controls in both normal and high-fat diet conditions, despite no significant changes in body weight and liver weight under chow diet. Ppp2cα(loxp/loxp): Alb mice showed enhanced glycogen deposition, serum triglyceride, cholesterol, low density lipoprotein and high density lipoprotein, activated insulin signaling, decreased expressions of gluconeogenic genes G6P and PEPCK, and lower liver triglyceride. Liver-specific Ppp2cα knockout mice showed enhanced glucose homeostasis and increased insulin sensitivity by activation of insulin signaling through Akt. These findings suggest that inhibition of hepatic Ppp2cα may be a useful strategy for the treatment of insulin resistance syndrome.
authors.affiliation: Key Laboratory of Model Animal for Disease Study of Ministry of Education, Model Animal Research Center, Nanjing University, Nanjing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xian
authors.affiliation: Key Laboratory of Model Animal for Disease Study of Ministry of Education, Model Animal Research Center, Nanjing University, Nanjing, China.
authors.forename: Siyuan
authors.initials: S
authors.lastname: Hou
authors.affiliation: Key Laboratory of Model Animal for Disease Study of Ministry of Education, Model Animal Research Center, Nanjing University, Nanjing, China.
authors.forename: Zan
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Key Laboratory of Model Animal for Disease Study of Ministry of Education, Model Animal Research Center, Nanjing University, Nanjing, China.
authors.forename: An
authors.initials: A
authors.lastname: Tang
authors.affiliation: Key Laboratory of Model Animal for Disease Study of Ministry of Education, Model Animal Research Center, Nanjing University, Nanjing, China.
authors.forename: Peiliang
authors.initials: P
authors.lastname: Shi
authors.affiliation: Key Laboratory of Model Animal for Disease Study of Ministry of Education, Model Animal Research Center, Nanjing University, Nanjing, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Key Laboratory of Model Animal for Disease Study of Ministry of Education, Model Animal Research Center, Nanjing University, Nanjing, China.
authors.forename: Anying
authors.initials: A
authors.lastname: Song
authors.affiliation: Key Laboratory of Model Animal for Disease Study of Ministry of Education, Model Animal Research Center, Nanjing University, Nanjing, China.
authors.forename: Shujun
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Model Animal for Disease Study of Ministry of Education, Model Animal Research Center, Nanjing University, Nanjing, China.
authors.forename: Zhaoyu
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Key Laboratory of Model Animal for Disease Study of Ministry of Education, Model Animal Research Center, Nanjing University, Nanjing, China.
authors.forename: Shiying
authors.initials: S
authors.lastname: Guo
authors.affiliation: Key Laboratory of Model Animal for Disease Study of Ministry of Education, Model Animal Research Center, Nanjing University, Nanjing, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
mesh_terms: D000818:Animals; D059305:Diet, High-Fat; D005947:Glucose / Q000378:metabolism*; D018149:Glucose Intolerance / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D000071636:Protein Phosphatase 2C; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D007328:Insulin; D008055:Lipids; D051057:Proto-Oncogene Proteins c-akt; D010749:Phosphoprotein Phosphatases; D000071636:Protein Phosphatase 2C; D005947:Glucose