Obesity rates are increasing at epidemic proportions, and this trend is accompanied by a cluster of diseases including type2 diabetes, cardiovascular disease and cancer. A common feature of obesity is hyperinsulinaemia, enabling glycaemic control to be maintained despite increasing adiposity and insulin resistance. A longstanding question is: what mechanisms coordinate the beta cell response to obesity and drive adaptive hyperinsulinaemia? We have recently identified the adipocyte-derived Fatty Acid Binding Protein 4 (FABP4) as having insulinotropic properties. In humans, we found that serum FABP4 levels correlate with GSIS and adiposity, suggesting a role for FABP4 in modulating the beta cell response during obesity. Furthermore, we have found that recombinant or adipocyte-derived FABP4 potentiates insulin secretion, and insulin reciprocally regulates FABP4 secretion. These data support a role for circulating FABP4 in forming an endocrine loop coordinating the beta cell response to adiposity. In addition, we have recently identified a cluster of SNPs in the FABP4 gene that significantly associate with type2 diabetes in humans, suggesting that alterations in this adaptive endocrine loop may contribute to diabetes risk.