Congiu Terenzio, Alghrably Mawadda, Emwas Abdul-Hamid, Jaremko Lukasz, Lachowicz Joanna I, Piludu Marco, Piras Monica, Faa Gavino, Pichiri Giuseppina, Jaremko Mariusz, Coni Pierpaolo
Department of Medical Sciences and Public Health, University of Cagliari, 09042 Monserrato, Italy.
Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.
Pharmaceutics. 2021 Jun 3;13(6):830. doi: 10.3390/pharmaceutics13060830.
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.
近几十年来，2型糖尿病并发症一直与胰淀素聚集、铜稳态和二甲双胍副作用相关。然而，每个因素都是单独分析的，只有在一些罕见的情况下才会考虑铜/胰淀素或铜/二甲双胍复合物。我们首次证明，具有高细胞毒性的二元二甲双胍/胰淀素和三元铜（II）/胰淀素/二甲双胍复合物会形成，并导致细胞膜上形成聚集的多层片状结构。考虑到2型糖尿病患者肾脏中胰淀素、铜（II）和二甲双胍浓度的增加，我们关于胰淀素及其加合物毒性的发现可能与糖尿病肾病的发展相关。
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