PMID- 26226221 OWN - NLM STAT- MEDLINE DCOM- 20160630 LR - 20211103 IS - 1873-3913 (Electronic) IS - 0898-6568 (Linking) VI - 27 IP - 11 DP - 2015 Nov TI - Kruppel-like factor 14 increases insulin sensitivity through activation of PI3K/Akt signal pathway. PG - 2201-8 LID - S0898-6568(15)00216-8 [pii] LID - 10.1016/j.cellsig.2015.07.019 [doi] AB - Genome-wide association studies (GWAS) have shown that Kruppel-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-3beta (GSK-3beta) 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. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Yang, Min AU - Yang M AD - Key Laboratory of Diagnostic Medicine (Ministry of Education) and Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, 400010 Chongqing, China. FAU - Ren, Yan AU - Ren Y AD - Key Laboratory of Diagnostic Medicine (Ministry of Education) and Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, 400010 Chongqing, China. FAU - Lin, Zhimin AU - Lin Z AD - Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, 400010 Chongqing, China. FAU - Tang, Chenchen AU - Tang C AD - Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, 400010 Chongqing, China. FAU - Jia, Yanjun AU - Jia Y AD - Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, 400010 Chongqing, China. FAU - Lai, Yerui AU - Lai Y AD - Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, 400010 Chongqing, China. FAU - Zhou, Tingting AU - Zhou T AD - Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, 400010 Chongqing, China. FAU - Wu, Shaobo AU - Wu S AD - Key Laboratory of Diagnostic Medicine (Ministry of Education) and Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, 400010 Chongqing, China. FAU - Liu, Hua AU - Liu H AD - Department of Pediatrics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505, USA. FAU - Yang, Gangyi AU - Yang G AD - Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, 400010 Chongqing, China. FAU - Li, Ling AU - Li L AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150728 PL - England TA - Cell Signal JT - Cellular signalling JID - 8904683 RN - 0 (Antigens, CD) RN - 0 (Chromones) RN - 0 (IRS1 protein, human) RN - 0 (Insulin) RN - 0 (Insulin Receptor Substrate Proteins) RN - 0 (KLF14 protein, human) RN - 0 (Kruppel-Like Transcription Factors) RN - 0 (Morpholines) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (RNA, Messenger) RN - 0 (Sp Transcription Factors) RN - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) RN - EC 2.7.10.1 (INSR protein, human) RN - EC 2.7.10.1 (Receptor, Insulin) RN - EC 2.7.11.1 (GSK3B protein, human) RN - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta) RN - EC 2.7.11.1 (Gsk3b protein, mouse) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.26 (Glycogen Synthase Kinase 3) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Adipose Tissue/metabolism MH - Animals MH - Antigens, CD/metabolism MH - Biological Transport/physiology MH - Cell Line, Tumor MH - Chromones/pharmacology MH - Diabetes Mellitus, Type 2/*pathology MH - Enzyme Activation MH - Glucose/metabolism MH - Glycogen Synthase Kinase 3/metabolism MH - Glycogen Synthase Kinase 3 beta MH - Humans MH - Insulin/metabolism MH - Insulin Receptor Substrate Proteins/metabolism MH - Insulin Resistance/*physiology MH - Kruppel-Like Transcription Factors MH - Mice MH - Mice, Inbred C57BL MH - Morpholines/pharmacology MH - Muscles/metabolism MH - Phosphatidylinositol 3-Kinases/*metabolism MH - Phosphoinositide-3 Kinase Inhibitors MH - Phosphorylation MH - Proto-Oncogene Proteins c-akt/*metabolism MH - RNA, Messenger/biosynthesis MH - Real-Time Polymerase Chain Reaction MH - Receptor, Insulin/metabolism MH - Signal Transduction/physiology MH - Sp Transcription Factors/*biosynthesis/genetics OTO - NOTNLM OT - Insulin resistance OT - Kruppel-like factor 14 OT - The PI3K/Akt pathway EDAT- 2015/08/01 06:00 MHDA- 2016/07/01 06:00 CRDT- 2015/07/31 06:00 PHST- 2015/04/20 00:00 [received] PHST- 2015/07/19 00:00 [revised] PHST- 2015/07/22 00:00 [accepted] PHST- 2015/07/31 06:00 [entrez] PHST- 2015/08/01 06:00 [pubmed] PHST- 2016/07/01 06:00 [medline] AID - S0898-6568(15)00216-8 [pii] AID - 10.1016/j.cellsig.2015.07.019 [doi] PST - ppublish SO - Cell Signal. 2015 Nov;27(11):2201-8. doi: 10.1016/j.cellsig.2015.07.019. Epub 2015 Jul 28.