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

Cell Signal. 2015 Nov;27(11):2201-8. doi: 10.1016/j.cellsig.2015.07.019. Epub 2015 Jul 28.


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.

Keywords: Insulin resistance; Krüppel-like factor 14; The PI3K/Akt pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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 / physiology*
  • Kruppel-Like Transcription Factors
  • Mice
  • Mice, Inbred C57BL
  • Morpholines / pharmacology
  • Muscles / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA, Messenger / biosynthesis
  • Real-Time Polymerase Chain Reaction
  • Receptor, Insulin / metabolism
  • Signal Transduction / physiology
  • Sp Transcription Factors / biosynthesis*
  • Sp Transcription Factors / genetics


  • Antigens, CD
  • Chromones
  • IRS1 protein, human
  • Insulin
  • Insulin Receptor Substrate Proteins
  • KLF14 protein, human
  • Kruppel-Like Transcription Factors
  • Morpholines
  • Phosphoinositide-3 Kinase Inhibitors
  • RNA, Messenger
  • Sp Transcription Factors
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • INSR protein, human
  • Receptor, Insulin
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, mouse
  • Proto-Oncogene Proteins c-akt
  • Glycogen Synthase Kinase 3
  • Glucose