PMID:16034410

Citation	Yang, Q, Graham, TE, Mody, N, Preitner, F, Peroni, OD, Zabolotny, JM, Kotani, K, Quadro, L and Kahn, BB (2005) Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature 436:356-62
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.
Links	PubMed Online version:10.1038/nature03711
Keywords	Adipose Tissue/drug effects; Adipose Tissue/metabolism; Animals; Diabetes Mellitus, Type 2/blood; Diabetes Mellitus, Type 2/metabolism; Disease Models, Animal; Gene Expression Regulation; Glucose Transporter Type 4; Hepatocytes/drug effects; Hepatocytes/enzymology; Hepatocytes/metabolism; Insulin/pharmacology; Insulin Resistance/physiology; Liver/cytology; Liver/drug effects; Liver/enzymology; Mice; Mice, Knockout; Monosaccharide Transport Proteins/deficiency; Monosaccharide Transport Proteins/genetics; Monosaccharide Transport Proteins/metabolism; Muscle Proteins/deficiency; Muscle Proteins/genetics; Muscle Proteins/metabolism; Muscles/drug effects; Muscles/metabolism; Obesity/blood; Obesity/metabolism; Oligonucleotide Array Sequence Analysis; Phosphoenolpyruvate Carboxykinase (GTP)/metabolism; Retinol-Binding Proteins/genetics; Retinol-Binding Proteins/metabolism; Retinol-Binding Proteins, Plasma; Signal Transduction/drug effects; Thiazolidinediones/pharmacology
edit table

Annotations

Gene product	Qualifier	GO ID	GO term name	Evidence Code	with/from	Aspect	Notes	Status
edit table

References

See Help:References for how to manage references in GONUTS.