Undercover Toxic Ménage à Trois of Amylin, Copper (II) and Metformin in Human Embryonic Kidney Cells
Terenzio Congiu,
Mawadda Alghrably,
Abdul-Hamid Emwas,
Lukasz Jaremko,
Joanna I. Lachowicz,
Marco Piludu,
Monica Piras,
Gavino Faa,
Giuseppina Pichiri,
Mariusz Jaremko,
Pierpaolo Coni
Affiliations
Terenzio Congiu
Department of Medical Sciences and Public Health, University of Cagliari, 09042 Monserrato, Italy
Mawadda Alghrably
Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia
Abdul-Hamid Emwas
Core Labs, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia
Lukasz Jaremko
Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia
Joanna I. Lachowicz
Department of Medical Sciences and Public Health, University of Cagliari, 09042 Monserrato, Italy
Marco Piludu
Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy
Monica Piras
Department of Medical Sciences and Public Health, University of Cagliari, 09042 Monserrato, Italy
Gavino Faa
Department of Medical Sciences and Public Health, University of Cagliari, 09042 Monserrato, Italy
Giuseppina Pichiri
Department of Medical Sciences and Public Health, University of Cagliari, 09042 Monserrato, Italy
Mariusz Jaremko
Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia
Pierpaolo Coni
Department of Medical Sciences and Public Health, University of Cagliari, 09042 Monserrato, Italy
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.