Investigating the roles of beta-cell Golgi stress in Type 1 Diabetes

Evidence indicates that islet autoimmunity in Type 1 diabetes arises from the failure of beta cells to withstand repeated episodes of stress signals, resulting in the loss of beta cell specific identify, function, and increased immunogenicity. The Golgi apparatus is an important site for protein post-translational modification, transport, and trafficking. The PI found that in human islets, suppression of the T1D susceptibility gene PGM1 triggers Golgi stress, highlighting its potential importance in mediating the development of T1D. However, unlike Endoplasmic Reticulum stress, the role of Golgi stress in beta cells has never been studied in detail. The hypothesis of this proposal is that Golgi stress impairs proinsulin processing, facilitates enteroviral replication, and that blocking GBF1/ARF prevents enteroviral infection in beta cells.