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Ekim Üstünel, B. ; Friedrich, K. ; Maida, A. ; Wang, X. ; Krones-Herzig, A. ; Seibert, O. ; Sommerfeld, A. ; Jones, A. ; Sijmonsma, T.P. ; Sticht, C.* ; Gretz, N.* ; Fleming, T.* ; Nawroth, P.P.* ; Stremmel, W.* ; Rose, A.J. ; Berriel-Diaz, M. ; Blüher, M.* ; Herzig, S.

Control of diabetic hyperglycaemia and insulin resistance through TSC22D4.

Nat. Commun. 7:13267 (2016)
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Open Access Gold
Creative Commons Lizenzvertrag
Obesity-related insulin resistance represents the core component of the metabolic syndrome, promoting glucose intolerance, pancreatic beta cell failure and type 2 diabetes. Efficient and safe insulin sensitization and glucose control remain critical therapeutic aims to prevent diabetic late complications Here, we identify transforming growth factor beta-like stimulated clone (TSC) 22 D4 as a molecular determinant of insulin signalling and glucose handling. Hepatic TSC22D4 inhibition both prevents and reverses hyperglycaemia, glucose intolerance and insulin resistance in diabetes mouse models. TSC22D4 exerts its effects on systemic glucose homeostasis - at least in part - through the direct transcriptional regulation of the small secretory protein lipocalin 13 (LCN13). Human diabetic patients display elevated hepatic TSC22D4 expression, which correlates with decreased insulin sensitivity, hyperglycaemia and LCN13 serum levels. Our results establish TSC22D4 as a checkpoint in systemic glucose metabolism in both mice and humans, and propose TSC22D4 inhibition as an insulin sensitizing option in diabetes therapy.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Metabolism; Obesity; Akt/pkb; Disease; Gene
Sprache deutsch
Veröffentlichungsjahr 2016
HGF-Berichtsjahr 2016
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 7, Heft: , Seiten: , Artikelnummer: 13267 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
POF Topic(s) 90000 - German Center for Diabetes Research
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-501900-251
Scopus ID 84995475195
Erfassungsdatum 2016-12-01