TY  - JOUR
AU  - Hasan, Sana S
AU  - Jabs, Markus
AU  - Taylor, Jacqueline
AU  - Wiedmann, Lena
AU  - Leibing, Thomas
AU  - Nordström, Viola
AU  - Federico, Giuseppina
AU  - Roma, Leticia P
AU  - Carlein, Christopher
AU  - Wolff, Gretchen
AU  - Ekim-Üstünel, Bilgen
AU  - Brune, Maik
AU  - Moll, Iris
AU  - Tetzlaff, Fabian
AU  - Gröne, Hermann-Josef
AU  - Fleming, Thomas
AU  - Géraud, Cyrill
AU  - Herzig, Stephan
AU  - Nawroth, Peter P
AU  - Fischer, Andreas
TI  - Endothelial Notch signaling controls insulin transport in muscle.
JO  - EMBO molecular medicine
VL  - 12
IS  - 4
SN  - 1757-4676
CY  - Heidelberg
PB  - EMBO Press
M1  - DKFZ-2020-00610
SP  - e09271
PY  - 2020
N1  - #EA:A270#LA:A270#2020 Apr 7;12(4):e09271
AB  - The role of the endothelium is not just limited to acting as an inert barrier for facilitating blood transport. Endothelial cells (ECs), through expression of a repertoire of angiocrine molecules, regulate metabolic demands in an organ-specific manner. Insulin flux across the endothelium to muscle cells is a rate-limiting process influencing insulin-mediated lowering of blood glucose. Here, we demonstrate that Notch signaling in ECs regulates insulin transport to muscle. Notch signaling activity was higher in ECs isolated from obese mice compared to non-obese. Sustained Notch signaling in ECs lowered insulin sensitivity and increased blood glucose levels. On the contrary, EC-specific inhibition of Notch signaling increased insulin sensitivity and improved glucose tolerance and glucose uptake in muscle in a high-fat diet-induced insulin resistance model. This was associated with increased transcription of Cav1, Cav2, and Cavin1, higher number of caveolae in ECs, and insulin uptake rates, as well as increased microvessel density. These data imply that Notch signaling in the endothelium actively controls insulin sensitivity and glucose homeostasis and may therefore represent a therapeutic target for diabetes.
LB  - PUB:(DE-HGF)16
C6  - pmid:32187826
DO  - DOI:10.15252/emmm.201809271
UR  - https://inrepo02.dkfz.de/record/154149
ER  -