Physiology and pathophysiology of beta cell apoptosis and its pharmacological intervention: Role of BH3-Only Proteins

This project investigated the specific involvement of BH3-only proteins in beta-cell apoptosis. BH3-only proteins are pro-apoptotic Bcl-2 family proteins and considered to be upstream initiators of the apoptotic cascade. In preliminary experiments we could demonstrate a potent, transcriptional induction of the BH3-only protein Bmf during apoptosis induced by a dominant-negative HNF-1alpha mutant. Bmf has been shown to be expressed physiologically in the kidney and pancreatic acinar cells, however a role in beta-cell apoptosis and in particular in type 1 and 2 diabetes models has not yet been described.

This project was funded by HRB.