Degradation of insulin amyloid by antibiotic minocycline and formation of toxic intermediates

Abstract Insulin balls, localized insulin amyloids formed at subcutaneous insulin-injection sites in patients with diabetes, cause poor glycemic control owing to impairments in insulin absorption. Our previous study has shown that some insulin balls are cytotoxic, but others are not, implying amyloi...

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Autores principales:	Wakako Mori, Keisuke Yuzu, Nadine Lobsiger, Hideo Nishioka, Hisako Sato, Terumasa Nagase, Keiichi Iwaya, Mikael Lindgren, Tamotsu Zako
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7235113440674dfc9f570e47401314da
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spelling	oai:doaj.org-article:7235113440674dfc9f570e47401314da2021-12-02T14:02:54ZDegradation of insulin amyloid by antibiotic minocycline and formation of toxic intermediates10.1038/s41598-021-86001-y2045-2322https://doaj.org/article/7235113440674dfc9f570e47401314da2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86001-yhttps://doaj.org/toc/2045-2322Abstract Insulin balls, localized insulin amyloids formed at subcutaneous insulin-injection sites in patients with diabetes, cause poor glycemic control owing to impairments in insulin absorption. Our previous study has shown that some insulin balls are cytotoxic, but others are not, implying amyloid polymorphism. Interestingly, the patient with toxic insulin balls had been treated with antibiotic minocycline, suggesting a possible relationship between toxicity of insulin balls and minocycline. However, the direct effect of minocycline on the structure and cytotoxicity of the insulin amyloid is still unclear. Herein, we demonstrated that that minocycline at physiological concentrations induced degradation of insulin amyloids formed from human insulin and insulin drug preparations used for diabetes patients. Interestingly, the process involved the initial appearance of the toxic species, which subsequently changed into less-toxic species. It is also shown that the structure of the toxic species was similar to that of sonicated fragments of human insulin amyloids. Our study shed new light on the clarification of the revelation of insulin balls and the development of the insulin analogs for diabetes therapy.Wakako MoriKeisuke YuzuNadine LobsigerHideo NishiokaHisako SatoTerumasa NagaseKeiichi IwayaMikael LindgrenTamotsu ZakoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wakako Mori Keisuke Yuzu Nadine Lobsiger Hideo Nishioka Hisako Sato Terumasa Nagase Keiichi Iwaya Mikael Lindgren Tamotsu Zako Degradation of insulin amyloid by antibiotic minocycline and formation of toxic intermediates
description	Abstract Insulin balls, localized insulin amyloids formed at subcutaneous insulin-injection sites in patients with diabetes, cause poor glycemic control owing to impairments in insulin absorption. Our previous study has shown that some insulin balls are cytotoxic, but others are not, implying amyloid polymorphism. Interestingly, the patient with toxic insulin balls had been treated with antibiotic minocycline, suggesting a possible relationship between toxicity of insulin balls and minocycline. However, the direct effect of minocycline on the structure and cytotoxicity of the insulin amyloid is still unclear. Herein, we demonstrated that that minocycline at physiological concentrations induced degradation of insulin amyloids formed from human insulin and insulin drug preparations used for diabetes patients. Interestingly, the process involved the initial appearance of the toxic species, which subsequently changed into less-toxic species. It is also shown that the structure of the toxic species was similar to that of sonicated fragments of human insulin amyloids. Our study shed new light on the clarification of the revelation of insulin balls and the development of the insulin analogs for diabetes therapy.
format	article
author	Wakako Mori Keisuke Yuzu Nadine Lobsiger Hideo Nishioka Hisako Sato Terumasa Nagase Keiichi Iwaya Mikael Lindgren Tamotsu Zako
author_facet	Wakako Mori Keisuke Yuzu Nadine Lobsiger Hideo Nishioka Hisako Sato Terumasa Nagase Keiichi Iwaya Mikael Lindgren Tamotsu Zako
author_sort	Wakako Mori
title	Degradation of insulin amyloid by antibiotic minocycline and formation of toxic intermediates
title_short	Degradation of insulin amyloid by antibiotic minocycline and formation of toxic intermediates
title_full	Degradation of insulin amyloid by antibiotic minocycline and formation of toxic intermediates
title_fullStr	Degradation of insulin amyloid by antibiotic minocycline and formation of toxic intermediates
title_full_unstemmed	Degradation of insulin amyloid by antibiotic minocycline and formation of toxic intermediates
title_sort	degradation of insulin amyloid by antibiotic minocycline and formation of toxic intermediates
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/7235113440674dfc9f570e47401314da
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Degradation of insulin amyloid by antibiotic minocycline and formation of toxic intermediates

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