We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Insulin Sensitivity Is Retained in Mice with Endothelial Loss of Carcinoembryonic Antigen Cell Adhesion Molecule 1.
- Authors
Muturi, Harrison T.; Khuder, Saja S.; Ghadieh, Hilda E.; Esakov, Emily L.; Noh, Hyelim; Kang, Heejoon; McInerney, Marcia F.; Kim, Jason K.; Lee, Abraham D.; Najjar, Sonia M.
- Abstract
CEACAM1 regulates endothelial barrier integrity. Because insulin signaling in extrahepatic target tissues is regulated by insulin transport through the endothelium, we aimed at investigating the metabolic role of endothelial CEACAM1. To this end, we generated endothelial cell-specific Ceacam1 null mice (VECadCre+Cc1fl/fl) and carried out their metabolic phenotyping and mechanistic analysis by comparison to littermate controls. Hyperinsulinemic-euglycemic clamp analysis showed intact insulin sensitivity in VECadCre+Cc1fl/fl mice. This was associated with the absence of visceral obesity and lipolysis and normal levels of circulating non-esterified fatty acids, leptin, and adiponectin. Whereas the loss of endothelial Ceacam1 did not affect insulin-stimulated receptor phosphorylation, it reduced IRS-1/Akt/eNOS activation to lower nitric oxide production resulting from limited SHP2 sequestration. It also reduced Shc sequestration to activate NF-κB and increase the transcription of matrix metalloproteases, ultimately inducing plasma IL-6 and TNFα levels. Loss of endothelial Ceacam1 also induced the expression of the anti-inflammatory CEACAM1-4L variant in M2 macrophages in white adipose tissue. Together, this could cause endothelial barrier dysfunction and facilitate insulin transport, sustaining normal glucose homeostasis and retaining fat accumulation in adipocytes. The data assign a significant role for endothelial cell CEACAM1 in maintaining insulin sensitivity in peripheral extrahepatic target tissues.
- Subjects
INSULIN sensitivity; CARCINOEMBRYONIC antigen; CELL adhesion molecules; INSULIN receptors; WHITE adipose tissue; HOMEOSTASIS; FAT cells
- Publication
Cells (2073-4409), 2021, Vol 10, Issue 8, p2093
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells10082093