Identification of novel insulin mimetic drugs by quantitative total internal reflection fluorescence (TIRF) microscopy

Peter Lanzerstorfer, Verena Stadlbauer, Lilia Chtcheglova, Renate Haselgrübler, Daniela Martina Borgmann, Jürgen Wruss, Peter Hinterdorfer, Klaus Schröder, Stephan Winkler, Otmar Höglinger, Julian Weghuber

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)


Background and Purpose Insulin stimulates the transport of glucose in target tissues by triggering the translocation of glucose transporter 4 (GLUT4) to the plasma membrane. Resistance to insulin, the major abnormality in type 2 diabetes, results in a decreased GLUT4 translocation efficiency. Thus, special attention is being paid to search for compounds that are able to enhance this translocation process in the absence of insulin. Experimental Approach Total internal reflection fluorescence (TIRF) microscopy was applied to quantify GLUT4 translocation in highly insulin-sensitive CHO-K1 cells expressing a GLUT4-myc-GFP fusion protein. Key Results Using our approach, we demonstrated GLUT4 translocation modulatory properties of selected substances and identified novel potential insulin mimetics. An increase in the TIRF signal was found to correlate with an elevated glucose uptake. Variations in the expression level of the human insulin receptor (hInsR) showed that the insulin mimetics identified stimulate GLUT4 translocation by a mechanism that is independent of the presence of the hInsR. Conclusions and Implications Taken together, the results indicate that TIRF microscopy is an excellent tool for the quantification of GLUT4 translocation and for identifying insulin mimetic drugs.

Original languageEnglish
Pages (from-to)5237-5251
Number of pages15
JournalBritish Journal of Pharmacology
Issue number23
Publication statusPublished - 1 Dec 2014


  • Androstadienes/pharmacology
  • Animals
  • CHO Cells
  • Chromones/pharmacology
  • Cricetulus
  • Glucose/metabolism
  • Glucose Transporter Type 4/metabolism
  • Green Fluorescent Proteins/metabolism
  • Humans
  • Insulin/pharmacology
  • Insulin Antagonists/pharmacology
  • Microscopy, Atomic Force
  • Microscopy, Fluorescence
  • Morpholines/pharmacology
  • Protein Transport
  • Proto-Oncogene Proteins c-myc/metabolism
  • Receptor, Insulin/metabolism
  • Wortmannin


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