Cathepsins in type 1 diabetes

​The gene encoding the lysosomal cysteine protease cathepsin H (CTSH) is a type 1 diabetes (T1D) candidate gene located at the susceptibility locus on chromosome 15q25.1. The project aims at understanding the roles of CTSH and other cathepsins for beta cell function and T1D risk.

​T1D affects more than 20 million people worldwide and develops because the insulin-producing pancreatic beta cells are destroyed by the immune system. The hypothesis behind this project is that T1D candidate genes have a major impact on the triggering and development of T1D by modulating the function and survival of the pancreatic beta cells when exposed to the immune system. By combining in vitro and in vivo experiments with clinical studies, we previously demonstrated that CTSH regulates beta cell function and disease progression in patients with newly-diagnosed T1D.
Our data suggest a protective role of CTSH in beta cells, but the precise mechanisms remain to be elucidated. Importantly, our results indicate that a high level of CTSH in beta cells affords protection against immune-mediated damage and preserve beta cell function, thereby representing a possible target for beta cell therapy in T1D.

Aim

The aim of this project is to characterize the cathepsin proteases and to understand their implication for beta cell dysfunction and T1D develop-ment.

Collaborators

Decio L. Eizirik, Université Libre de Bruxelles, Brussels, Belgium.
Thomas Reinheckel, Albert-Ludwigs-University, Freiburg, Germany.

Funding

The Danish Council for Independent Research (DFF-4183-00031)
The European Foundation for the Study of Diabetes (EFSD)
Læge Sofus Carl Emil Friis & Hustru Olga Doris Friis Legat
Vissing Fonden
Aase og Ejnar Danielsens Fond



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