{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T21:18:20Z","timestamp":1773350300288,"version":"3.50.1"},"reference-count":74,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T00:00:00Z","timestamp":1622678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/pharmaceutics13060830","type":"journal-article","created":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T21:03:32Z","timestamp":1622754212000},"page":"830","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Undercover Toxic M\u00e9nage \u00e0 Trois of Amylin, Copper (II) and Metformin in Human Embryonic Kidney Cells"],"prefix":"10.3390","volume":"13","author":[{"given":"Terenzio","family":"Congiu","sequence":"first","affiliation":[{"name":"Department of Medical Sciences and Public Health, University of Cagliari, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mawadda","family":"Alghrably","sequence":"additional","affiliation":[{"name":"Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9231-3850","authenticated-orcid":false,"given":"Abdul-Hamid","family":"Emwas","sequence":"additional","affiliation":[{"name":"Core Labs, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lukasz","family":"Jaremko","sequence":"additional","affiliation":[{"name":"Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4644-761X","authenticated-orcid":false,"given":"Joanna I.","family":"Lachowicz","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Public Health, University of Cagliari, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Piludu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy"},{"name":"Consorzio Interuniversitario per lo Sviluppo dei Sistemi a Grande Interfase (CSGI), via della Lastruccia 3, 50019 Sesto Fiorentino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Piras","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Public Health, University of Cagliari, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gavino","family":"Faa","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Public Health, University of Cagliari, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppina","family":"Pichiri","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Public Health, University of Cagliari, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariusz","family":"Jaremko","sequence":"additional","affiliation":[{"name":"Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierpaolo","family":"Coni","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Public Health, University of Cagliari, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S79","DOI":"10.2337\/diacare.27.2007.S79","article-title":"Nephropathy in diabetes","volume":"27","author":"Association","year":"2004","journal-title":"Diabetes Care"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.1681\/ASN.2008111186","article-title":"The Role of the Mammalian Target of Rapamycin (mTOR) in Renal Disease","volume":"20","author":"Lieberthal","year":"2009","journal-title":"J. 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