Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes

Qin Yang, Timothy E. Graham, Nimesh Mody, Frederic Preitner, Odile D. Peroni, Janice M. Zabolotny, Ko Kotani, Loredana Quadro and Barbara B. Kahn ()
Additional contact information
Qin Yang: Beth Israel Deaconess Medical Center and Harvard Medical School
Timothy E. Graham: Beth Israel Deaconess Medical Center and Harvard Medical School
Nimesh Mody: Beth Israel Deaconess Medical Center and Harvard Medical School
Frederic Preitner: Beth Israel Deaconess Medical Center and Harvard Medical School
Odile D. Peroni: Beth Israel Deaconess Medical Center and Harvard Medical School
Janice M. Zabolotny: Beth Israel Deaconess Medical Center and Harvard Medical School
Ko Kotani: Beth Israel Deaconess Medical Center and Harvard Medical School
Loredana Quadro: Columbia University
Barbara B. Kahn: Beth Israel Deaconess Medical Center and Harvard Medical School

Nature, 2005, vol. 436, issue 7049, 356-362

Abstract: Abstract In obesity and type 2 diabetes, expression of the GLUT4 glucose transporter is decreased selectively in adipocytes. Adipose-specific Glut4 (also known as Slc2a4) knockout (adipose-Glut4-/-) mice show insulin resistance secondarily in muscle and liver. Here we show, using DNA arrays, that expression of retinol binding protein-4 (RBP4) is elevated in adipose tissue of adipose-Glut4-/- mice. We show that serum RBP4 levels are elevated in insulin-resistant mice and humans with obesity and type 2 diabetes. RBP4 levels are normalized by rosiglitazone, an insulin-sensitizing drug. Transgenic overexpression of human RBP4 or injection of recombinant RBP4 in normal mice causes insulin resistance. Conversely, genetic deletion of Rbp4 enhances insulin sensitivity. Fenretinide, a synthetic retinoid that increases urinary excretion of RBP4, normalizes serum RBP4 levels and improves insulin resistance and glucose intolerance in mice with obesity induced by a high-fat diet. Increasing serum RBP4 induces hepatic expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) and impairs insulin signalling in muscle. Thus, RBP4 is an adipocyte-derived ‘signal’ that may contribute to the pathogenesis of type 2 diabetes. Lowering RBP4 could be a new strategy for treating type 2 diabetes.

Date: 2005
References: Add references at CitEc
Citations: View citations in EconPapers (8)

Downloads: (external link)
https://www.nature.com/articles/nature03711 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

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:nature:v:436:y:2005:i:7049:d:10.1038_nature03711

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

DOI: 10.1038/nature03711

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

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