Insulin Sensitivity Is Retained in Mice with Endothelial Loss of Carcinoembryonic Antigen Cell Adhesion Molecule 1.

Autor: Muturi HT; Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA., Khuder SS; Center for Diabetes and Endocrine Research, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43606, USA., Ghadieh HE; Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA., Esakov EL; Center for Diabetes and Endocrine Research, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43606, USA.; Department of Medicinal and Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences, Toledo, OH 43606, USA., Noh H; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA., Kang H; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.; Department of Breast-Endocrine Surgery, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong 18450, Korea., McInerney MF; Center for Diabetes and Endocrine Research, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43606, USA.; Department of Medicinal and Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences, Toledo, OH 43606, USA., Kim JK; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.; Division of Endocrinology, Metabolism and Diabetes, University of Massachusetts Medical School, Worcester, MA 01605, USA., Lee AD; Department of Rehabilitation Sciences, Judith Herb College of Education, Human Science and Human Service, The University of Toledo, Toledo, OH 43606, USA., Najjar SM; Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA.; Center for Diabetes and Endocrine Research, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43606, USA.; Diabetes Institute, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA.
Jazyk: angličtina
Zdroj: Cells [Cells] 2021 Aug 14; Vol. 10 (8). Date of Electronic Publication: 2021 Aug 14.
DOI: 10.3390/cells10082093
Abstrakt: 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+Cc1 fl/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+Cc1 fl/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.
Databáze: MEDLINE
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