Modulation of insulin degrading enzyme activity and liver cell proliferation

  1. Pivovarova, Olga
  2. von Loeffelholz, Christian
  3. Ilkavets, Iryna
  4. Sticht, Carsten
  5. Zhuk, Sergei
  6. Murahovschi, Veronica
  7. Lukowski, Sonja
  8. Döcke, Stephanie
  9. Kriebel, Jennifer
  10. de Gala, Tonia las Heras
  11. Malashicheva, Anna
  12. Kostareva, Anna
  13. Lock, Johan F
  14. Stockmann, Martin
  15. Grallert, Harald
  16. Gretz, Norbert
  17. Dooley, Steven
  18. Pfeiffer, Andreas FH
  19. Rudovich, Natalia

WeightNameValue
1000 Titel
  • Modulation of insulin degrading enzyme activity and liver cell proliferation
1000 Autor/in
  1. Pivovarova, Olga |
  2. von Loeffelholz, Christian |
  3. Ilkavets, Iryna |
  4. Sticht, Carsten |
  5. Zhuk, Sergei |
  6. Murahovschi, Veronica |
  7. Lukowski, Sonja |
  8. Döcke, Stephanie |
  9. Kriebel, Jennifer |
  10. de Gala, Tonia las Heras |
  11. Malashicheva, Anna |
  12. Kostareva, Anna |
  13. Lock, Johan F |
  14. Stockmann, Martin |
  15. Grallert, Harald |
  16. Gretz, Norbert |
  17. Dooley, Steven |
  18. Pfeiffer, Andreas FH |
  19. Rudovich, Natalia |
1000 Erscheinungsjahr 2015
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2015-05-06
1000 Erschienen in
1000 Quellenangabe
  • 14(14): 2293-2300
1000 FRL-Sammlung
1000 Verlagsversion
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613656/ |
  • http://dx.doi.org/10.1080/15384101.2015.1046647 |
1000 Ergänzendes Material
  • http://www.tandfonline.com/doi/full/10.1080/15384101.2015.1046647#supplemental-material-section |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Diabetes mellitus type 2 (T2DM), insulin therapy, and hyperinsulinemia are independent risk factors of liver cancer. Recently, the use of a novel inhibitor of insulin degrading enzyme (IDE) was proposed as a new therapeutic strategy in T2DM. However, IDE inhibition might stimulate liver cell proliferation via increased intracellular insulin concentration. The aim of this study was to characterize effects of inhibition of IDE activity in HepG2 hepatoma cells and to analyze liver specific expression of IDE in subjects with T2DM. HepG2 cells were treated with 10 nM insulin for 24 h with or without inhibition of IDE activity using IDE RNAi, and cell transcriptome and proliferation rate were analyzed. Human liver samples (n = 22) were used for the gene expression profiling by microarrays. In HepG2 cells, IDE knockdown changed expression of genes involved in cell cycle and apoptosis pathways. Proliferation rate was lower in IDE knockdown cells than in controls. Microarray analysis revealed the decrease of hepatic IDE expression in subjects with T2DM accompanied by the downregulation of the p53-dependent genes FAS and CCNG2, but not by the upregulation of proliferation markers MKI67, MCM2 and PCNA. Similar results were found in the liver microarray dataset from GEO Profiles database. In conclusion, IDE expression is decreased in liver of subjects with T2DM which is accompanied by the dysregulation of p53 pathway. Prolonged use of IDE inhibitors for T2DM treatment should be carefully tested in animal studies regarding its potential effect on hepatic tumorigenesis.
1000 Sacherschließung
lokal hepatocellular carcinoma
lokal type 2 diabetes mellitus
lokal insulin-degrading enzyme
lokal proliferation
lokal non-alcoholic fatty liver disease
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
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1000 Label
1000 Förderer
  1. German Diabetic Association |
  2. German Ministry of Education and Science (BMBF) |
1000 Fördernummer
  1. -
  2. ROS10-058 GERUSSFIT
1000 Förderprogramm
  1. Allgemeine Projektförderung der DDG 2011; Allgemeine Projektförderung der DDG 2012
  2. -
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer German Diabetic Association |
    1000 Förderprogramm Allgemeine Projektförderung der DDG 2011; Allgemeine Projektförderung der DDG 2012
    1000 Fördernummer -
  2. 1000 joinedFunding-child
    1000 Förderer German Ministry of Education and Science (BMBF) |
    1000 Förderprogramm -
    1000 Fördernummer ROS10-058 GERUSSFIT
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6405488.rdf
1000 Erstellt am 2017-11-24T11:32:08.766+0100
1000 Erstellt von 122
1000 beschreibt frl:6405488
1000 Bearbeitet von 288
1000 Zuletzt bearbeitet 2021-03-30T11:51:01.451+0200
1000 Objekt bearb. Tue Mar 30 11:51:01 CEST 2021
1000 Vgl. frl:6405488
1000 Oai Id
  1. oai:frl.publisso.de:frl:6405488 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

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