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00925njm 22002777a 4500 dc Mukherjee, Abhisek author Morales-Scheihing, Diego author Salvadores, Natalia author Moreno-Gonzalez, Ines author Gonzalez, Cesar author Taylor-Presse, Kaithlyn author Mendez, Nicolas author Shahnawaz, Mohamed author Gaber, Ahmed Osama author Sabek, Omaima author Fraga, Daniel W author Soto, Claudio author 2017 Although a large proportion of patients with type 2 diabetes (T2D) accumulate misfolded aggregates composed of the islet amyloid polypeptide (IAPP), its role in the disease is unknown. Here, we show that pancreatic IAPP aggregates can promote the misfolding and aggregation of endogenous IAPP in islet cultures obtained from transgenic mouse or healthy human pancreas. Islet homogenates immunodepleted with anti-IAPP–specific antibodies were not able to induce IAPP aggregation. Importantly, intraperitoneal inoculation of pancreatic homogenates containing IAPP aggregates into transgenic mice expressing human IAPP dramatically accelerates IAPP amyloid deposition, which was accompanied by clinical abnormalities typical of T2D, including hyperglycemia, impaired glucose tolerance, and a substantial reduction on β cell number and mass. Finally, induction of IAPP deposition and diabetic abnormalities were also induced in vivo by administration of IAPP aggregates prepared in vitro using pure, synthetic IAPP. Our findings suggest that some of the pathologic and clinical alterations of T2D might be transmissible through a similar mechanism by which prions propagate in prion diseases. Mukherjee, A., Morales-Scheihing, D., Salvadores, N., Moreno-Gonzalez, I., Gonzalez, C., Taylor-Presse, K., Mendez, N., Shahnawaz, M., Gaber, A. O., Sabek, O. M., Fraga, D. W., & Soto, C. (2017). Induction of IAPP amyloid deposition and associated diabetic abnormalities by a prion-like mechanism. Journal of Experimental Medicine, 214(9), 2591-2610. https://hdl.handle.net/10630/37402 10.1084/JEM.20161134 Diabetes Induction of IAPP amyloid deposition and associated diabetic abnormalities by a prion-like mechanism