Role of retinol-binding protein 4 in the pathogenesis of Type 2 diabetes

Abstract

Retinol-binding protein (RBP)4 is a new adipocytokine that has been associated with insulin resistance. Both RBP4 mRNA expression in adipocytes and serum RBP4 levels are elevated in adipose-specific glucose transporter 4-knockout mice, and elevated circulating RBP4 levels cause insulin resistance by inhibiting phosphatidylinositol 3 kinase activity in skeletal muscle and increasing phosphoenolpyruvate carboxylase expression in liver. Several clinical cross-sectional studies have shown a significant negative association between circulating RBP4 levels and insulin sensitivity evaluated by the glucose clamp method, but it is unclear if RBP4 is associated with insulin resistance in humans because of many conflicting results. Drugs such as rosiglitazone, exercise and weight loss have been shown to decrease circulating RBP4 levels and improve insulin resistance, but contradictory results have been found in other studies. In addition, a recent clinical study has suggested that RBP4 is more closely related to visceral adiposity than subcutaneous adiposity. In summary, RBP4 is an adipocytokine that is especially associated with visceral fat and may be associated with insulin resistance in humans. However, this association remains uncertain and whether or not RBP4 is a new target for treatment of Type 2 diabetes remains to be determined.