title: Staurosporine as an agonist for induction of GLUT4 translocation, identified by a pH-sensitive fluorescent IRAP-mOrange2 probe.
abstract: Insulin-stimulated GLUT4 translocation from GLUT4 storage vesicles (GSVs) to the plasma membrane (PM) constitutes a key process for blood glucose control. Therefore, compounds that could promote GLUT4 translocation into the PM represent potential drugs for the treatment of diabetes. In this research, we screened for agonists that induce GLUT4 translocation by using a novel pH-sensitive fluorescent probe, insulin-regulated aminopeptidase (IRAP)-mOrange2. We identified as well as validated one agonist, staurosporine, from a 64,000 compound library. Staurosporine promotes GSVs translocation into the PM and increases glucose uptake through the AMP-activated protein kinase (AMPK) pathway, serving as an effective insulin additive analogue in L6 cells. Our work highlights the convenience and efficiency of this novel pH-sensitive fluorescent probe and reveals the new biological activity of staurosporine as an agonist for GLUT4 translocation and as an effective insulin additive analogue.
authors: College of Life Science, Sichuan Normal University, Chengdu 610101, China; National Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors: Yufeng
authors: Y
authors: Li
authors: National Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors: Li
authors: L
authors: Zheng
authors: National Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors: Dan
authors: D
authors: Wang
authors: National Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors: Xiang
authors: X
authors: Zhang
authors: State Key Laboratory of Drug Research, The National Drug Screening Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
authors: Jia
authors: J
authors: Li
authors: National Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors: Sher
authors: S
authors: Ali
authors: National Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors: Jingze
authors: J
authors: Lu
authors: College of Life Science, Sichuan Normal University, Chengdu 610101, China. Electronic address: zonghaocsd@163.com.
authors: Hao
authors: H
authors: Zong
authors: National Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: xiaolanxu@moon.ibp.ac.cn.
authors: Xiaolan
authors: X
authors: Xu
mesh_terms: D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D005947:Glucose / Q000493:pharmacokinetics*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives; D053590:Interleukin 1 Receptor Antagonist Protein / Q000493:pharmacokinetics*; D008164:Luminescent Proteins / Q000493:pharmacokinetics*; D008856:Microscopy, Fluorescence; D021381:Protein Transport / Q000187:drug effects; D019311:Staurosporine / Q000032:analysis / Q000494:pharmacology*
chemical_list: D005456:Fluorescent Dyes; D051275:Glucose Transporter Type 4; C507763:IL1RN protein, human; D007328:Insulin; D053590:Interleukin 1 Receptor Antagonist Protein; D008164:Luminescent Proteins; C495692:SLC2A4 protein, human; C413663:fluorescent protein 583; D019311:Staurosporine; D005947:Glucose
keywords: Diabetes; GLUT4 translocation; Insulin additive analogue; Staurosporine; pH-sensitive fluorescent probe