Buchumschlag

TSC22D4 interacts with Akt1 to regulate glucose metabolism

Weitere Versionen anzeigen (2)

Maladaptive insulin signaling is a key feature in the pathogenesis of severe metabolic disorders, including obesity and diabetes. Enhancing insulin sensitivity represents a major goal in the treatment of patients affected by diabetes. Here, we identify transforming growth factor-β1 stimulated clone...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Hauptverfasser: Demir, Sevgican (VerfasserIn) , Wolff, Gretchen (VerfasserIn) , Wieder, Annika (VerfasserIn) , Maida, Adriano (VerfasserIn) , Bühler, Lea (VerfasserIn) , Brune, Maik (VerfasserIn) , Hautzinger, Oksana (VerfasserIn) , Feuchtinger, Annette (VerfasserIn) , Poth, Tanja (VerfasserIn) , Szendrödi, Julia (VerfasserIn) , Herzig, Stephan (VerfasserIn) , Üstünel, Bilgen Ekim (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 21 October 2022
In: Science advances
Year: 2022, Jahrgang: 8, Heft: 42, Pages: 1-15
ISSN:2375-2548
DOI:10.1126/sciadv.abo5555
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1126/sciadv.abo5555
Verlag, lizenzpflichtig, Volltext: https://www.science.org/doi/10.1126/sciadv.abo5555
Volltext
Verfasserangaben:Sevgican Demir, Gretchen Wolff, Annika Wieder, Adriano Maida, Lea Bühler, Maik Brune, Oksana Hautzinger, Annette Feuchtinger, Tanja Poth, Julia Szendroedi, Stephan Herzig, Bilgen Ekim Üstünel
Beschreibung
Zusammenfassung:Maladaptive insulin signaling is a key feature in the pathogenesis of severe metabolic disorders, including obesity and diabetes. Enhancing insulin sensitivity represents a major goal in the treatment of patients affected by diabetes. Here, we identify transforming growth factor-β1 stimulated clone 22 D4 (TSC22D4) as a novel interaction partner for protein kinase B/Akt1, a critical mediator of insulin/phosphatidylinositol 3-kinase signaling pathway. While energy deprivation and oxidative stress promote the TSC22D4-Akt1 interaction, refeeding mice or exposing cells to glucose and insulin impairs this interaction, which relies on an intrinsically disordered region (D2 domain) within TSC22D4. Functionally, the interaction with TSC22D4 reduces basal phosphorylation of Akt and its downstream targets during starvation, thereby promoting insulin sensitivity. Genetic, liver-specific reconstitution experiments in mice demonstrate that the interaction between TSC22D4 and Akt1 improves glucose handling and insulin sensitivity. Overall, our findings postulate a model whereby TSC22D4 acts as an environmental sensor and interacts with Akt1 to regulate insulin signaling and glucose metabolism.
Beschreibung:Gesehen am 20.01.2023
Beschreibung:Online Resource
ISSN:2375-2548
DOI:10.1126/sciadv.abo5555

Ähnliche Einträge