title: CD226 reduces endothelial cell glucose uptake under hyperglycemic conditions with inflammation in type 2 diabetes mellitus.
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.
authors.affiliation: Department of Aerospace Medicine, Fourth Military Medical University, Xi'an, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Zilong
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Department of Immunology, Fourth Military Medical University Xi'an, China.
authors.forename: Jinxue
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Aerospace Medicine, Fourth Military Medical University, Xi'an, China.
authors.forename: Yizheng
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Immunology, Fourth Military Medical University Xi'an, China.
authors.forename: Boquan
authors.initials: B
authors.lastname: Jin
authors.affiliation: Department of Aerospace Medicine, Fourth Military Medical University, Xi'an, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Shuzhong
authors.initials: S
authors.lastname: Guo
authors.affiliation: Department of Immunology, Fourth Military Medical University Xi'an, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Zhuang
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D059305:Diet, High-Fat; D042783:Endothelial Cells; D005260:Female; D005947:Glucose / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000098862:T Lineage-Specific Activation Antigen 1
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; D014409:Tumor Necrosis Factor-alpha; D005947:Glucose
keywords: CD226; Pathology Section; endothelial cells; high fat diet; type 2 diabetes mellitus