Insulin and insulin-like growth factor I have complementary roles in the regulation of glucose homeostasis. Observational studies suggest that patients with type II diabetes have lower levels of circulating IGF-I. IGF-I is also believed to have a direct effect on insulin sensitivity. IGF bioavailability is modulated by a family of binding proteins, most acutely by IGFBP-1 which is also regulated by insulin and nutritional status. We assessed the longitudinal changes in IGF-I, IGF-I sensitivity and IGFBP-1 expression in dietary-induced obesity in mice. Male C57 Bl/6 mice received an obesogenic diet and were compared with chow-fed controls (6-16 per group). Body weight and fat pad mass were recorded. Insulin sensitivity was assessed by insulin tolerance tests. Fasting IGF-I levels were measured by ELISA and hepatic IGFBP-1 expression was measured by real-time PCR. Subcutaneous IGF-I tolerance tests (0.2g/μg) were also performed. All animals were humanely killed. Results are shown in Table 1, with p<0.05 considered significant. Mice receiving a high-fat diet had a higher body weight and fat pad mass. Insulin resistance as assessed by hypoglycaemic response to exogenous insulin was increased at 4 and 8 weeks. The hypoglycaemic effect of IGF-I was significantly diminished and IGF-I levels were found to be significantly higher. There was no difference in hepatic IGFBP-1 expression. These data, contrary to previously reported observations suggest that IGF-I levels increase as insulin sensitivity decreases and there is an accompanying decrease in IGF-I sensitivity.