title: Involvement of KLF11 in hepatic glucose metabolism in mice via suppressing of PEPCK-C expression.
abstract: BACKGROUND
  Abnormal hepatic gluconeogenesis is related to hyperglycemia in mammals with insulin resistance. Despite the strong evidences linking Krüppel-like factor 11 (KLF11) gene mutations to development of Type 2 diabetes, the precise physiological functions of KLF11 in vivo remain largely unknown.
  
  
  RESULTS
  In current investigation, we showed that KLF11 is involved in modulating hepatic glucose metabolism in mice. Overexpression of KLF11 in primary mouse hepatocytes could inhibit the expression of gluconeogenic genes, including phosphoenolpyruvate carboxykinase (cytosolic isoform, PEPCK-C) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), subsequently decreasing the cellular glucose output. Diabetic mice with overexpression of KLF11 gene in livers significantly ameliorated hyperglycemia and glucose intolerance; in contrast, the knockdown of KLF11 expression in db/m and C57BL/6J mice livers impaired glucose tolerance.
  
  
  CONCLUSIONS
  Our data strongly indicated the involvement of KLF11 in hepatic glucose homeostasis via modulating the expression of PEPCK-C.
authors.affiliation: Department of Biochemistry & Molecular Biology, School of Basic Medicine, Anhui Medical University, Hefei, China ; National Laboratory of Medical Molecular Biology, Institute of Basic Medical Science, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
authors.forename: Huabing
authors.initials: H
authors.lastname: Zhang
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Science, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Science, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiao
authors.affiliation: Department of Biochemistry, Jining Medical University, Jining, China.
authors.forename: Anfang
authors.initials: A
authors.lastname: Cui
authors.affiliation: Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing Digestive Disease Center, Beijing, China.
authors.forename: Xiujing
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Chemistry, School of Basic Medicine, Anhui Medical University, Hefei, China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Fang
authors.affiliation: Integrative and Molecular Physiology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Liwei
authors.initials: L
authors.lastname: Xie
authors.affiliation: Department of Endocrinology, The Hospital Affiliated to Liaoning University of Traditional Chinese Medicine, Shenyang, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Science, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
authors.forename: Fude
authors.initials: F
authors.lastname: Fang
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Science, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Chang
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism / Q000473:pathology*; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; C506460:KLF11 protein, mouse; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D014157:Transcription Factors; C069767:phosphoenolpyruvate carboxylase kinase; D017346:Protein Serine-Threonine Kinases; D005947:Glucose