title: Krüppel-like factor 14 increases insulin sensitivity through activation of PI3K/Akt signal pathway.
abstract: Genome-wide association studies (GWAS) have shown that Krüppel-like factor 14 (KLF14) is associated with type 2 diabetes mellitus (T2DM). However, no report has demonstrated a relationship between KLF14 and glucose metabolism. The aim of this study was to determine whether KLF14 is associated with glucose metabolism and insulin signaling in vitro. The mRNA and protein expressions of KLF14 were determined by Real-time PCR and Western blotting. Glucose uptake was assessed by 2-[(3)H]-deoxyglucose (2-DG) uptake. Western blotting was used to identify the activation of insulin signaling proteins. KLF14 mRNA and protein in fat and muscle were significantly decreased in HFD-fed mice, db/db mice and T2DM patients. Overexpression of KLF14 enhanced insulin-stimulated glucose uptake and the activation of Akt kinase in Hepa1-6 cells. The phosphorylation of insulin receptor (InsR), insulin receptor substrate-1(IRS-1), glycogen synthase kinase-3β (GSK-3β) and Akt also elevated significantly by up-regulation of KLF14. KLF14 overexpression in Hepa1-6 cells prevented the inhibition of glucose uptake and Akt phosphorylation induced by high glucose and/or high insulin, or T2DM serum. However, KLF14's ability to increase glucose uptake and Akt activation was significantly attenuated by LY294002, a PI3-kinase inhibitor. These data suggested that KLF14 could increase insulin sensitivity probably through the PI3K/Akt pathway.
authors.affiliation: Key Laboratory of Diagnostic Medicine (Ministry of Education) and Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, 400010 Chongqing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.affiliation: Key Laboratory of Diagnostic Medicine (Ministry of Education) and Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, 400010 Chongqing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, 400010 Chongqing, China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, 400010 Chongqing, China.
authors.forename: Chenchen
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, 400010 Chongqing, China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, 400010 Chongqing, China.
authors.forename: Yerui
authors.initials: Y
authors.lastname: Lai
authors.affiliation: Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, 400010 Chongqing, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Diagnostic Medicine (Ministry of Education) and Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, 400010 Chongqing, China.
authors.forename: Shaobo
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Pediatrics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, 400010 Chongqing, China.
authors.forename: Gangyi
authors.initials: G
authors.lastname: Yang
authors.affiliation: Key Laboratory of Diagnostic Medicine (Ministry of Education) and Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, 400010 Chongqing, China. Electronic address: liling31@hotmail.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D008810:Mice, Inbred C57BL; D009025:Morpholines / Q000494:pharmacology; D009132:Muscles / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D060888:Real-Time Polymerase Chain Reaction; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D051703:Sp Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D015703:Antigens, CD; D002867:Chromones; D005947:Glucose; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D051741:Kruppel-Like Transcription Factors; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D011972:Receptor, Insulin; D051703:Sp Transcription Factors; C526292:IRS1 protein, human; C417549:KLF14 protein, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C435941:INSR protein, human; C000605506:GSK3B protein, human; C000605507:Gsk3b protein, mouse
keywords: Insulin resistance; Krüppel-like factor 14; The PI3K/Akt pathway