Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes - PubMed (original) (raw)
. 2005 Jul 21;436(7049):356-62.
doi: 10.1038/nature03711.
Affiliations
- PMID: 16034410
- DOI: 10.1038/nature03711
Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes
Qin Yang et al. Nature. 2005.
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.
Comment in
- Metabolism: A is for adipokine.
Muoio DM, Newgard CB. Muoio DM, et al. Nature. 2005 Jul 21;436(7049):337-8. doi: 10.1038/436337a. Nature. 2005. PMID: 16034406 No abstract available.
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