Oncotarget

Research Papers: Pathology:

CD226 reduces endothelial cell glucose uptake under hyperglycemic conditions with inflammation in type 2 diabetes mellitus

Yuan Zhang, Tian Liu, Yu Chen, Zilong Dong, Jinxue Zhang, Yizheng Sun, Boquan Jin, Feng Gao, Shuzhong Guo and Ran Zhuang _

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Oncotarget. 2016; 7:12010-12023. https://doi.org/10.18632/oncotarget.7505

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Abstract

Yuan Zhang1,*, Tian Liu2,*, Yu Chen3,*, Zilong Dong4, Jinxue Zhang5, Yizheng Sun1, Boquan Jin5, Feng Gao1, Shuzhong Guo2 and Ran Zhuang5

1 Department of Aerospace Medicine, Fourth Military Medical University, Xi’an, China

2 Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, China

3 Department of Gastroenterology, Xijing Hospital, Fourth Military Medical University, Xi’an, China

4 Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi’an, China

5 Department of Immunology, Fourth Military Medical University Xi’an, China

* These authors have contributed equally to this work

Correspondence to:

Ran Zhuang, email:

Keywords: CD226, high fat diet, type 2 diabetes mellitus, endothelial cells, Pathology Section

Received: May 13, 2015 Accepted: January 26, 2016 Published: February 19, 2016

Abstract

CD226 is a co-stimulatory adhesion molecule found on immune and endothelial cells. Here, we evaluated a possible role for CD226 in inhibiting glucose uptake in isolated human umbilical vein endothelial cells (HUVECs) and in wild-type (WT) and CD226 knockout (KO) mice with high-fat diet (HFD)-induced type 2 diabetes (T2DM). CD226 expression increased under hyperglycemic conditions in the presence of TNF-α. Furthermore, CD226 knockdown improved glucose uptake in endothelial cells, and CD226 KO mice exhibited increased glucose tolerance. Levels of soluble CD226 in plasma were higher in T2DM patients following an oral glucose tolerance test (OGTT) than under fasting conditions. Our results indicate that low-grade inflammation coupled with elevated blood glucose increases CD226 expression, resulting in decreased endothelial cell glucose uptake in T2DM.


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