Abstract

Brief Summary

"T-cadherin in the Pancreas: Role in Islet Development, Regeneration and the Pathogenesis of Type 2 Diabetes"

Diabetes, particularly Type 2, is epidemic throughout the world. It is clear that failure of the pancreatic insulin-producing cells, i.e. the ß-cells play a critical role in the development of diabetes. Revealing the molecular mechanisms underlying ß-cell function may provide insight into the reasons for ß-cell failure in diabetes.

These studies seek to explain the role of a particular protein, T-cadherin, in ß-cells. When the T-cadherin gene is eliminated in mice, they develop diabetes at age 3 to 5 months. The explanation of this phenomenon is not yet clear, but experimental evidence points toward a malfunction of ß-cell insulin secretion. Moreover, T-cadherin has an atypical distribution within the ß-cells of normal mice. Usually, cadherins are found on the surface of cells and are involved in cell-to-cell interactions. In ß-cells, T-cadherin is instead found in the cytoplasm in a fashion that resembles the distribution of insulin granules. If this can be established, it is reasonable to postulate that T-cadherin is directly involved in the process of insulin secretion, and is a possible explanation for the altered insulin secretion and presence of diabetes in these mice.