Research Papers

Undercover Toxic Ménage à Trois of Amylin, Copper (II) and Metformin in Human Embryonic Kidney Cells

by Terenzio Congiu, Mawadda Alghrably, Abdul-Hamid Emwas, Łukasz Jaremko, Joanna Izabela Lachowicz, Marco Piludu, Monica Piras, Gavino Faa, Giuseppina Pichiri, Mariusz Jaremko, Pierpaolo Coni
Pharmaceutics Year: 2021 DOI: 10.3390/pharmaceutics13060830

Extra Information

Research article


In recent decades, type 2 diabetes complications have been correlated with amylin aggregation, copper homeostasis and metformin side effects. However, each factor was analyzed separately, and only in some rare cases copper/amylin or copper/metformin complexes were considered. We demonstrate for the first time that binary metformin/amylin and tertiary copper (II)/amylin/metformin complexes of high cellular toxicity are formed and lead to the formation of aggregated multi-level lamellar structures on the cell membrane. Considering the increased concentration of amylin, copper (II) and metformin in kidneys of T2DM patients, our findings on the toxicity of amylin and its adducts may be correlated with diabetic nephropathy development.


diabetic nephropathy (DN) metformin copper human islet amyloid polypeptide (hIAPP) metal complexes