title: Knockdown of STEAP4 inhibits insulin-stimulated glucose transport and GLUT4 translocation via attenuated phosphorylation of Akt, independent of the effects of EEA1.
abstract: The aim of this study was to investigate whether the early endosome antigen 1 (EEA1) and/or PI3K pathway is involved in the molecular mechanisms underlying the effects of the six-transmembrane protein of prostate 4 (STEAP4; also called STAMP2 and TIARP) on the insulin sensitivity of human adipocytes. Our data demonstrated that siRNA-mediated STEAP4 deficiency significantly decreased insulin-stimulated glucose transport in mature human adipocytes by decreasing GLUT4 translocation to the plasma membrane through attenuated Akt phosphorylation. We further found that EEA1 may not be involved in the mechanisms underlying the effects of STEAP4 on insulin-stimulated glucose uptake and GLUT4 translocation, as indicated by the results that i) STEAP4 does not alter the effects of EEA1 on insulin-stimulated glucose uptake and GLUT4 translocation; ii) STEAP4 does not modify the expression of EEA1 protein; and iii) STEAP4 does not interact with EEA1 according to FRET analysis. In conclusion, this study revealed that the knockdown of STEAP4 inhibits insulin-stimulated glucose transport and GLUT4 translocation via the attenuated phosphorylation of Akt, independent of the effects of EEA1.
authors.affiliation: Department of Newborn Infants, Nanjing Children's Hospital of Nanjing Medical University, Nanjing 210008, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Cheng
authors.forename: Jie
authors.initials: J
authors.lastname: Qiu
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Zhou
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Chen
authors.forename: Chun
authors.initials: C
authors.lastname: Zhu
authors.forename: Da-Ni
authors.initials: DN
authors.lastname: Qin
authors.forename: Ji-Wu
authors.initials: JW
authors.lastname: Wang
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Ni
authors.forename: Chen-Bo
authors.initials: CB
authors.lastname: Ji
authors.forename: Xi-Rong
authors.initials: XR
authors.lastname: Guo
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000201:enzymology; D001692:Biological Transport / Q000187:drug effects; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008565:Membrane Proteins / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D008565:Membrane Proteins; C495692:SLC2A4 protein, human; D033921:Vesicular Transport Proteins; C093846:early endosome antigen 1; D010088:Oxidoreductases; C503310:STEAP4 protein, human; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose