Insulin amyloid polymorphs: implications for iatrogenic cytotoxicity. Issue 62 (12th October 2020)

• Record Type: Journal Article
• Authors: Yuzu, Keisuke; Lindgren, Mikael; Nyström, Sofie; Zhang, Jun; Mori, Wakako; Kunitomi, Risako; Nagase, Terumasa; Iwaya, Keiichi; Hammarström, Per; Zako, Tamotsu
• Is Part Of: RSC advances. Volume 10:Issue 62(2020)
• Page Start: 37721
• Page End: 37727
• Publication Date: 2020-10-12
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d0ra07742a
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : Structural polymorphism of insulin amyloids in vivo can be recognized using novel amyloid specific fluorescent probes, pFTAA and BTD21. Abstract : Amyloid specific fluorescent probes are becoming an important tool for studies of disease progression and conformational polymorphisms in diseases related to protein misfolding and aggregation such as localized and systemic amyloidosis. Herein, it is demonstrated that using the amyloid specific fluorescent probes pFTAA and benzostyryl capped benzothiadiazole BTD21, structural polymorphisms of insulin amyloids are imaged in localized insulin-derived amyloid aggregates formed at subcutaneous insulin-injection sites in patients with diabetes. It is also found that pFTAA and BTD21 could discriminate structural polymorphisms of insulin amyloids, so called fibrils and filaments, formed in vitro . In addition, it is shown that insulin drug preparations used for treating diabetes formed various types of amyloid aggregates that can be assessed and quantified using pFTAA and BTD21. Interestingly, incubated pFTAA-positive insulin preparation aggregates show cytotoxicity while BTD21-positive aggregates are less toxic. From these observations, a variety of amyloid polymorphic structures with different cytotoxicities formed both in vivo and in vitro by various insulin preparations are proposed.