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01.06.2015 | Original Article

NETosis is induced by high glucose and associated with type 2 diabetes

verfasst von: Lisa Menegazzo, Stefano Ciciliot, Nicol Poncina, Marta Mazzucato, Mariasara Persano, Benedetta Bonora, Mattia Albiero, Saula Vigili de Kreutzenberg, Angelo Avogaro, Gian Paolo Fadini

Erschienen in: Acta Diabetologica | Ausgabe 3/2015

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Abstract

Aims

The role of neutrophils in diabetes and its complications is unclear. Upon challenge with microbes and inflammatory triggers, neutrophils release enzymes and nuclear material, forming neutrophils extracellular traps (NETs) and thereby dying by NETosis. We herein tested NET formation and NETosis products in high glucose and in the setting of type 2 diabetes (T2D).

Methods

NETosis was assessed in vitro in cells exposed to 0, 5, 25 mM glucose and 25 mM mannitol, DMSO and PMA using immunofluorescence staining for elastase, DNA and chromatin. Single-cell morphometric analysis was used to detect enter of elastase in the nucleus and extrusion of nuclear material. Release of NETs was quantified by staining with Hoechst 33342. In 38 T2D and 38 age- and sex-matched non-diabetic individuals, we determined plasma elastase, mono- and oligonucleosomes and double-strand (ds) DNA, as circulating NETosis products.

Results

NETosis was accurately reproduced in vitro: high (25 mM) glucose increased NETosis rate and release of NETs compared with 5 mM glucose and 25 mM mannitol. T2D patients showed increased plasma elastase, mono- and oligonucleosomes and dsDNA compared with non-diabetic control individuals. A positive correlation was found between HbA_1c and mono- and oligonucleosomes, whereas dsDNA was correlated with the presence of nephropathy and cardiovascular disease. Serum IL-6 concentrations were higher in T2D compared with CTRL and correlated with serum dsDNA levels.

Conclusions

High glucose and hyperglycemia increase release of NETs and circulating markers of NETosis, respectively. This finding provides a link among neutrophils, inflammation and tissue damage in diabetes.

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Titel: NETosis is induced by high glucose and associated with type 2 diabetes
verfasst von: Lisa Menegazzo
Stefano Ciciliot
Nicol Poncina
Marta Mazzucato
Mariasara Persano
Benedetta Bonora
Mattia Albiero
Saula Vigili de Kreutzenberg
Angelo Avogaro
Gian Paolo Fadini
Publikationsdatum: 01.06.2015
Verlag: Springer Milan
Erschienen in: Acta Diabetologica / Ausgabe 3/2015
Print ISSN: 0940-5429
Elektronische ISSN: 1432-5233
DOI: https://doi.org/10.1007/s00592-014-0676-x

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NETosis is induced by high glucose and associated with type 2 diabetes

Abstract

Aims

Methods

Results

Conclusions

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Parodontalbehandlung verbessert Prognose bei Katheterablation

Antihypertensiva schützen auch alte Menschen noch vor Demenz

Stereotaktische Radiatio schlägt konventionelle Bestrahlung

Denken Sie bei starker Blutung auch an die Hemmkörper-Hämophilie

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Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

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Abstract

Aims

Methods

Results

Conclusions

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