Endothelium-specific depletion of LRP1 improves glucose homeostasis through inducing osteocalcin.
Nat Commun
; 12(1): 5296, 2021 09 06.
Article
em En
| MEDLINE
| ID: mdl-34489478
ABSTRACT
The vascular endothelium is present within metabolic organs and actively regulates energy metabolism. Here we show osteocalcin, recognized as a bone-secreted metabolic hormone, is expressed in mouse primary endothelial cells isolated from heart, lung and liver. In human osteocalcin promoter-driven green fluorescent protein transgenic mice, green fluorescent protein signals are enriched in endothelial cells lining aorta, small vessels and capillaries and abundant in aorta, skeletal muscle and eye of adult mice. The depletion of lipoprotein receptor-related protein 1 induces osteocalcin through a Forkhead box O -dependent pathway in endothelial cells. Whereas depletion of osteocalcin abolishes the glucose-lowering effect of low-density lipoprotein receptor-related protein 1 depletion, osteocalcin treatment normalizes hyperglycemia in multiple mouse models. Mechanistically, osteocalcin receptor-G protein-coupled receptor family C group 6 member A and insulin-like-growth-factor-1 receptor are in the same complex with osteocalcin and required for osteocalcin-promoted insulin signaling pathway. Therefore, our results reveal an endocrine/paracrine role of endothelial cells in regulating insulin sensitivity, which may have therapeutic implications in treating diabetes and insulin resistance through manipulating vascular endothelium.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Endotélio Vascular
/
Osteocalcina
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Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade
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Células Endoteliais
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Glucose
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Hiperglicemia
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Nat Commun
Ano de publicação:
2021
Tipo de documento:
Article