Serum retinol-binding protein: a link between obesity, insulin resistance, and type 2 diabetes.

Insulin resistance occurs under conditions of obesity, metabolic syndrome, and type 2 diabetes. It was found to be accompanied by down-regulation of the insulin-responsive glucose transporter GLUT4. Decreased adipocyte GLUT4 caused secretion by adipocytes of the serum retinol-binding protein RBP4. Enhanced levels of serum RBP4 appeared to be the signal for the development of systemic insulin resistance both in experimental animals and in humans. In mice, increased levels of serum RBP4 led to impaired glucose uptake into skeletal muscle and increased glucose production by liver, whereas lowered serum RBP4 levels greatly enhanced insulin sensitivity. Thus, a link has been established between obesity and insulin resistance: RBP4, the vitamin A-transport protein secreted into the circulation by adipocytes.