Download
125_2015_Article_3703.pdf 1,48MB
WeightNameValue
1000 Titel
  • The diabetes gene Zfp69 modulates hepatic insulin sensitivity in mice
1000 Autor/in
  1. Chung, Bomee |
  2. Stadion, Mandy |
  3. Schulz, Nadja |
  4. Jain, Deepak |
  5. Scherneck, Stephan |
  6. Schürmann, Annette |
  7. Joost, Hans-Georg |
1000 Erscheinungsjahr 2015
1000 Art der Datei
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2015-08-01
1000 Erschienen in
1000 Quellenangabe
  • 58(10): 2403–2413
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2015
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1007/s00125-015-3703-8 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4572078/ |
1000 Ergänzendes Material
  • https://link.springer.com/article/10.1007%2Fs00125-015-3703-8#SupplementaryMaterial |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • AIMS/HYPOTHESIS: Zfp69 was previously identified by positional cloning as a candidate gene for obesity-associated diabetes. C57BL/6J and New Zealand obese (NZO) mice carry a loss-of-function mutation due to the integration of a retrotransposon. On the NZO background, the Zfp69 locus caused severe hyperglycaemia and loss of beta cells. To provide direct evidence for a causal role of Zfp69, we investigated the effects of its overexpression on both a lean [B6-Tg(Zfp69)] and an obese [NZO/B6-Tg(Zfp69)] background. METHODS: Zfp69 transgenic mice were generated by integrating the cDNA into the ROSA locus of the C57BL/6 genome and characterised. RESULTS: B6-Tg(Zfp69) mice were normoglycaemic, developed hyperinsulinaemia, and exhibited increased expression of G6pc and Pck1 and slightly reduced phospho-Akt levels in the liver. During OGTTs, glucose clearance was normal but insulin levels were significantly higher in the B6-Tg(Zfp69) than in control mice. The liver fat content and plasma triacylglycerol levels were significantly increased in B6-Tg(Zfp69) and NZO/B6-Tg(Zfp69) mice on a high-fat diet compared with controls. Liver transcriptome analysis of B6-Tg(Zfp69) mice revealed a downregulation of genes involved in glucose and lipid metabolism. Specifically, expression of Nampt, Lpin2, Map2k6, Gys2, Bnip3, Fitm2, Slc2a2, Ppargc1α and Insr was significantly decreased in the liver of B6-Tg(Zfp69) mice compared with wild-type animals. However, overexpression of Zfp69 did not induce overt diabetes with hyperglycaemia and beta cell loss. CONCLUSIONS/INTERPRETATION: Zfp69 mediates hyperlipidaemia, liver fat accumulation and mild insulin resistance. However, it does not induce type 2 diabetes, suggesting that the diabetogenic effect of the Zfp69 locus requires synergy with other as yet unidentified genes.
1000 Sacherschließung
lokal Zfp69
lokal Hepatosteatosis
lokal Insulin resistance
lokal Diabetes
lokal Lipid metabolism
1000 Fachgruppe
  1. Biologie |
  2. Medizin |
  3. Ernährungswissenschaften |
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/creator/Q2h1bmcsIEJvbWVl|https://frl.publisso.de/adhoc/creator/U3RhZGlvbiwgTWFuZHk=|https://frl.publisso.de/adhoc/creator/U2NodWx6LCBOYWRqYQ==|https://frl.publisso.de/adhoc/creator/SmFpbiwgRGVlcGFr|https://frl.publisso.de/adhoc/creator/U2NoZXJuZWNrLCBTdGVwaGFu|https://frl.publisso.de/adhoc/creator/U2Now7xybWFubiwgQW5uZXR0ZQ==|http://orcid.org/0000-0002-5860-606X
1000 Förderer
  1. German Federal Ministry of Education and Research (BMBF) |
  2. State of Brandenburg, Germany |
1000 Fördernummer
  1. 01GS0821; 01GI0847; 01GI0922; 01GI0925
  2. -
1000 Förderprogramm
  1. NGFNplus; NEUROTARGET; DZD
  2. -
1000 Dateien
  1. The diabetes gene Zfp69 modulates hepatic insulin sensitivity in mice
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer German Federal Ministry of Education and Research (BMBF) |
    1000 Förderprogramm NGFNplus; NEUROTARGET; DZD
    1000 Fördernummer 01GS0821; 01GI0847; 01GI0922; 01GI0925
  2. 1000 joinedFunding-child
    1000 Förderer State of Brandenburg, Germany |
    1000 Förderprogramm -
    1000 Fördernummer -
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6405041.rdf
1000 Erstellt am 2017-10-16T16:51:14.094+0200
1000 Erstellt von 218
1000 beschreibt frl:6405041
1000 Bearbeitet von 218
1000 Zuletzt bearbeitet Wed Jun 27 10:29:24 CEST 2018
1000 Objekt bearb. Wed Jun 27 10:29:24 CEST 2018
1000 Vgl. frl:6405041
1000 Oai Id
  1. oai:frl.publisso.de:frl:6405041 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

View source