RT Journal Article
T1 Induction of IAPP amyloid deposition and associated diabetic abnormalities by a prion-like mechanism
A1 Mukherjee, Abhisek
A1 Morales-Scheihing, Diego
A1 Salvadores, Natalia
A1 Moreno-Gonzalez, Ines
A1 Gonzalez, Cesar
A1 Taylor-Presse, Kaithlyn
A1 Mendez, Nicolas
A1 Shahnawaz, Mohamed
A1 Gaber, Ahmed Osama
A1 Sabek, Omaima
A1 Fraga, Daniel W
A1 Soto, Claudio
K1 Diabetes
AB 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.
PB Rockefeller University PRess
YR 2017
FD 2017
LK https://hdl.handle.net/10630/37402
UL https://hdl.handle.net/10630/37402
LA eng
NO 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.
NO This study was supported in part by the Jeane B. Kempner postdoctoral fellowship awarded to A. Mukherjee. National Institute of General Medical Sciences United States  R01GM100453 to CS.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 3 mar 2026