Control of diabetic hyperglycaemia and insulin resistance through TSC22D4

Bilgen Ekim Üstünel, Kilian Friedrich, Adriano Maida, Xiaoyue Wang, Anja Krones-Herzig, Oksana Seibert, Anke Sommerfeld, Allan Jones, Tjeerd P. Sijmonsma, Carsten Sticht, Norbert Gretz, Thomas Fleming, Peter P. Nawroth, Wolfgang Stremmel, Adam J. Rose, Mauricio Berriel-Diaz, Matthias Blüher and Stephan Herzig ()
Additional contact information
Bilgen Ekim Üstünel: Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, and Joint Heidelberg-IDC Translational Diabetes Program
Kilian Friedrich: Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, and Joint Heidelberg-IDC Translational Diabetes Program
Adriano Maida: Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, and Joint Heidelberg-IDC Translational Diabetes Program
Xiaoyue Wang: Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, and Joint Heidelberg-IDC Translational Diabetes Program
Anja Krones-Herzig: Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, and Joint Heidelberg-IDC Translational Diabetes Program
Oksana Seibert: Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, and Joint Heidelberg-IDC Translational Diabetes Program
Anke Sommerfeld: Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, and Joint Heidelberg-IDC Translational Diabetes Program
Allan Jones: Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, and Joint Heidelberg-IDC Translational Diabetes Program
Tjeerd P. Sijmonsma: Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, and Joint Heidelberg-IDC Translational Diabetes Program
Carsten Sticht: Center for Clinical Research, Medical Faculty Mannheim
Norbert Gretz: Center for Clinical Research, Medical Faculty Mannheim
Thomas Fleming: Heidelberg University
Peter P. Nawroth: Heidelberg University
Wolfgang Stremmel: Heidelberg University Hospital
Adam J. Rose: Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, and Joint Heidelberg-IDC Translational Diabetes Program
Mauricio Berriel-Diaz: Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, and Joint Heidelberg-IDC Translational Diabetes Program
Matthias Blüher: University of Leipzig
Stephan Herzig: Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, and Joint Heidelberg-IDC Translational Diabetes Program

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: Abstract 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.

Date: 2016
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms13267 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13267

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms13267

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().