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Ordelheide, A.-M. ; Gerst, F.* ; Rothfuss, O.* ; Heni, M.* ; Haas, C. ; Thielker, I. ; Herzberg-Schäfer, S.* ; Böhm, A. ; Machicao, F. ; Ullrich, S. ; Stefan, N. ; Fritsche, A. ; Häring, H.-U. ; Staiger, H.

Nor-1, a novel incretin-responsive regulator of insulin genes and insulin secretion.

Mol. Metab. 2, 243-255 (2013)
Verlagsversion Volltext DOI PMC
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B-cell failure at the onset of type 2 diabetes is caused by a decline in β-cell function in the postprandial state and loss of pancreatic β-cell mass. Recently, we showed an association between increased insulin secretion and a single nucleotide polymorphism (SNP), SNP rs12686676, in the NR4A3 gene locus encoding the nuclear receptor Nor-1. Nor-1 is expressed in β-cells, however, not much is known about its function with regard to insulin gene expression and insulin secretion. Nor-1 is induced in a glucose-/incretin-dependent manner via the PKA pathway and directly induces insulin gene expression. Additionally, it stimulates insulin secretion possibly via regulation of potentially important genes in insulin exocytosis. Moreover, we show that the minor allele of NR4A3 SNP rs12686676 fully rescues incretin resistance provoked by a well-described polymorphism in TCF7L2. Thus, Nor-1 represents a promising new target for pharmacological intervention to fight diabetes.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Nor-1; Insulin gene expression; Insulin secretion; Incretin resistance; TCF7L2
Sprache englisch
Veröffentlichungsjahr 2013
HGF-Berichtsjahr 0
ISSN (print) / ISBN 2212-8778
e-ISSN 2212-8778
Zeitschrift Molecular Metabolism
Quellenangaben Band: 2, Heft: 3, Seiten: 243-255 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research and Metabolic Diseases (IDM)
POF Topic(s) 90000 - German Center for Diabetes Research
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-502400-002
G-502400-001
PubMed ID 24044104
DOI 10.1016/j.molmet.2013.06.003
Erfassungsdatum 2013-12-17
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