RBP4

Retinol-binding protein 4 (RBP4), an adipocyte-derived factor, plays a pivotal role in insulin resistance and the pathogenesis of type 2 diabetes. In adipose-specific GLUT4 knockout (Glut4?/?) mice, RBP4 expression is markedly elevated, and increased circulating RBP4 levels are observed in insulin-resistant mice and humans with obesity and type 2 diabetes. Conversely, reducing RBP4 levels through genetic deletion or pharmacological intervention (e.g., fenretinide) enhances insulin sensitivity and improves glucose homeostasis. Mechanistically, RBP4 disrupts insulin signaling in muscle and induces hepatic gluconeogenesis via phosphoenolpyruvate carboxykinase (PEPCK) upregulation. These findings suggest that targeting RBP4 could represent a novel therapeutic approach for improving insulin sensitivity and managing type 2 diabetes.