Abstract

Obesity is a key factor in the development of insulin resistance. Resistance to the vascular effects of insulin plays a central role in the initiation and progression of cardiovascular disease. Developing novel therapeutic strategies to prevent and treat insulin resistance is therefore important. IGFBP-1 (Insulin like growth factor binding protein 1) is a 30kDa protein, derived mainly from the liver. In humans, the circulating concentration of IGFBP-1 has been proposed as a marker of insulin sensitivity. IGFBP-1 can impact on cellular functions via an RGD (α5β1 integrin binding) motif independent of IGF binding. We have previously shown that in vivo over expression of IGFBP-1 improves insulin sensitivity, promotes nitric oxide production, lowers blood pressure and protects against atherosclerosis. In the series of studies presented here, complementary in vitro and in vivo approaches were used to explore the effect and mechanism of I GFBP-1 on metabolic homeostasis and angiogenesis.