Krüppel-like factor 14 increases insulin sensitivity through activation of PI3K/Akt signal pathway

• Published in: Cellular signalling 2015-11, Vol.27 (11), p.2201-2208
• Main Authors: Yang, Min, Ren, Yan, Lin, Zhimin, Tang, Chenchen, Jia, Yanjun, Lai, Yerui, Zhou, Tingting, Wu, Shaobo, Liu, Hua, Yang, Gangyi, Li, Ling
• Format: Article
• Language: English
• Subjects: Adipose Tissue - metabolism; Animals; Antigens, CD - metabolism; Biological Transport - physiology; Cell Line, Tumor; Chromones - pharmacology; Diabetes Mellitus, Type 2 - pathology; Enzyme Activation; Glucose - metabolism; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 beta; Humans; Insulin - metabolism; Insulin Receptor Substrate Proteins - metabolism; Insulin resistance; Insulin Resistance - physiology; Krüppel-like factor 14; Mice; Mice, Inbred C57BL; Morpholines - pharmacology; Muscles - metabolism; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Proto-Oncogene Proteins c-akt - metabolism; Real-Time Polymerase Chain Reaction; Receptor, Insulin - metabolism; RNA, Messenger - biosynthesis; Signal Transduction - physiology; Sp Transcription Factors - biosynthesis; Sp Transcription Factors - genetics; The PI3K/Akt pathway
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2015.07.019

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-[3H]-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. •Genome-wide association studies have shown that KLF14 is associated with T2DM.•It is the first report of KLF14 in glucose metabolism and insulin signaling pathway.•We investigated the expressions of KLF14 in mice and T2DM subjects.•We evaluated the effects of KLF14 on glucose uptake and insulin signaling.•KLF14 might increase insulin sensitivity through the PI3K/Akt pathway.