Loss of bone morphogenetic protein-binding endothelial regulator causes insulin resistance

Hua Mao, Luge Li, Qiying Fan, Aude Angelini, Pradip K. Saha, Huaizhu Wu, Christie M. Ballantyne, Sean M. Hartig, Liang Xie and Xinchun Pi ()
Additional contact information
Hua Mao: Department of Medicine, Section of Athero & Lipo, Baylor College of Medicine
Luge Li: Department of Medicine, Section of Athero & Lipo, Baylor College of Medicine
Qiying Fan: Department of Medicine, Section of Athero & Lipo, Baylor College of Medicine
Aude Angelini: Department of Medicine, Section of Athero & Lipo, Baylor College of Medicine
Pradip K. Saha: Department of Medicine, Division of Diabetes, Endocrinology & Metabolism, Diabetes Research Center, Baylor College of Medicine
Huaizhu Wu: Department of Medicine, Section of Athero & Lipo, Baylor College of Medicine
Christie M. Ballantyne: Department of Medicine, Section of Athero & Lipo, Baylor College of Medicine
Sean M. Hartig: Department of Medicine, Division of Diabetes, Endocrinology & Metabolism, Diabetes Research Center, Baylor College of Medicine
Liang Xie: Department of Medicine, Section of Athero & Lipo, Baylor College of Medicine
Xinchun Pi: Department of Medicine, Section of Athero & Lipo, Baylor College of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-10

Abstract: Abstract Accumulating evidence suggests that chronic inflammation of metabolic tissues plays a causal role in obesity-induced insulin resistance. Yet, how specific endothelial factors impact metabolic tissues remains undefined. Bone morphogenetic protein (BMP)–binding endothelial regulator (BMPER) adapts endothelial cells to inflammatory stress in diverse organ microenvironments. Here, we demonstrate that BMPER is a driver of insulin sensitivity. Both global and endothelial cell-specific inducible knockout of BMPER cause hyperinsulinemia, glucose intolerance and insulin resistance without increasing inflammation in metabolic tissues in mice. BMPER can directly activate insulin signaling, which requires its internalization and interaction with Niemann-Pick C1 (NPC1), an integral membrane protein that transports intracellular cholesterol. These results suggest that the endocrine function of the vascular endothelium maintains glucose homeostasis. Of potential translational significance, the delivery of BMPER recombinant protein or its overexpression alleviates insulin resistance and hyperglycemia in high-fat diet-fed mice and Leprdb/db (db/db) diabetic mice. We conclude that BMPER exhibits therapeutic potential for the treatment of diabetes.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-22130-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22130-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-22130-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().