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000154149 0247_ $$2doi$$a10.15252/emmm.201809271
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000154149 041__ $$aeng
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000154149 1001_ $$0P:(DE-HGF)0$$aHasan, Sana S$$b0$$eFirst author
000154149 245__ $$aEndothelial Notch signaling controls insulin transport in muscle.
000154149 260__ $$aHeidelberg$$bEMBO Press$$c2020
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000154149 520__ $$aThe 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.
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000154149 7001_ $$0P:(DE-He78)91fcd65e6bc5ac8458df2a71d0d143d9$$aJabs, Markus$$b1$$eFirst author
000154149 7001_ $$0P:(DE-He78)df29352b13734f9202e3b900aeef7754$$aTaylor, Jacqueline$$b2$$udkfz
000154149 7001_ $$0P:(DE-He78)b27922c32bcdf07ca4d5f13ecdcfd100$$aWiedmann, Lena$$b3$$udkfz
000154149 7001_ $$aLeibing, Thomas$$b4
000154149 7001_ $$0P:(DE-He78)9bce4efcbedb17d7b4d0d7832c136faf$$aNordström, Viola$$b5
000154149 7001_ $$0P:(DE-He78)616706c4d6f7bdf68b30893f860cbb2b$$aFederico, Giuseppina$$b6
000154149 7001_ $$aRoma, Leticia P$$b7
000154149 7001_ $$aCarlein, Christopher$$b8
000154149 7001_ $$aWolff, Gretchen$$b9
000154149 7001_ $$aEkim-Üstünel, Bilgen$$b10
000154149 7001_ $$aBrune, Maik$$b11
000154149 7001_ $$0P:(DE-He78)68d90eb013f51c689f9ebea83a920858$$aMoll, Iris$$b12$$udkfz
000154149 7001_ $$0P:(DE-He78)2ccbbfe1b8852c4d003e0dde043a7f17$$aTetzlaff, Fabian$$b13
000154149 7001_ $$0P:(DE-He78)00a2ea610aee4a8fca32908fc3d02e91$$aGröne, Hermann-Josef$$b14
000154149 7001_ $$aFleming, Thomas$$b15
000154149 7001_ $$aGéraud, Cyrill$$b16
000154149 7001_ $$aHerzig, Stephan$$b17
000154149 7001_ $$00000-0002-6134-7804$$aNawroth, Peter P$$b18
000154149 7001_ $$0P:(DE-He78)039283a5d51058ec79156d0ef67132da$$aFischer, Andreas$$b19$$eLast author$$udkfz
000154149 773__ $$0PERI:(DE-600)2485479-7$$a10.15252/emmm.201809271$$n4$$pe09271$$tEMBO molecular medicine$$v12$$x1757-4676$$y2020
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