TY - JOUR
T1 - Undercover Toxic Ménage à Trois of Amylin, Copper (II) and Metformin in Human Embryonic Kidney Cells
AU - Congiu, Terenzio
AU - Alghrably, Mawadda N.
AU - Emwas, Abdul-Hamid M.
AU - Jaremko, Lukasz
AU - Lachowicz, Joanna Izabela
AU - Piludu, Marco
AU - Piras, Monica
AU - Faa, Gavino
AU - Pichiri, Giuseppina
AU - Jaremko, Mariusz
AU - Coni, Pierpaolo
N1 - KAUST Repository Item: Exported on 2021-06-07
Acknowledgements: This research was partially funded by FIR 2020 and from Regione Autonoma della Sardegna (grant RASSR79857).
PY - 2021/6/3
Y1 - 2021/6/3
N2 - 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.
AB - 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.
UR - http://hdl.handle.net/10754/669367
UR - https://www.mdpi.com/1999-4923/13/6/830
U2 - 10.3390/pharmaceutics13060830
DO - 10.3390/pharmaceutics13060830
M3 - Article
C2 - 34204936
SN - 1999-4923
VL - 13
SP - 830
JO - Pharmaceutics
JF - Pharmaceutics
IS - 6
ER -