...Here, we report that IAPP can be incorporated to multivesicular bodies (MVB) and secreted into exosomes, a mechanism responsible for the exportation of these toxic aggregates as vehicles of cell to cell communication. On this regard, we have demonstrated that the exosomes bearing toxic hIAPP released from pancreatic β cells are capable to induce hyperactivation of mTORC1 signaling, a failure in the autophagic cellular quality control, and favor pro-fission status of the mitochondrial dynamics in hippocampal cells. In summary, our results show that harmful accumulation of hIAPP in pancreatic β cells may be detoxified by the release of exosomes, which may be captured by endocytosis mechanism damaging neuronal hippocampal cells, which suggest an underlying molecular mechanism to the link between type 2 diabetes and neurodegenerative diseases.