Type 2 diabetes mellitus is reaching epidemic proportions; however, we still know relatively little about the exact mechanisms by which the disease develops. One key step leading to the development of type 2 diabetes is that cells lose the ability to release insulin in response to glucose. However, the reason for this is unknown, although recent genetic studies have provided clues. One of the most prominent genetic risk factors is in the TCF7L2 gene, but it is not known how this leads to diabetes. Our recent work has identified a novel way by which glucose controls insulin release by regulating a protein called catenin. This has led us to develop a highly novel hypothesis as to how the TCF7L2 gene defects might affect insulin secretion. We will use animal studies to test this hypothesis, and we believe this will solve an important missing link in understanding how type 2 diabetes develops.