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Doctoral Thesis
DOI
10.11606/T.42.2016.tde-06092016-094234
Document
Author
Full name
Arnaldo Henrique de Souza
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2016
Supervisor
Committee
Carpinelli, Angelo Rafael (President)
Carneiro, Everardo Magalhães
Giannella, Maria Lucia Cardillo Correa
Lopes, Lucia Rossetti
Ortis, Fernanda
Title in Portuguese
Modulação redox, função e sobrevivência de células β-pancreáticas: evidência sobre o papel da enzima NADPH oxidase-2 (NOX2) em um modelo in vitro de glicotoxicidade.
Keywords in Portuguese
Apoptose
Célula-β
Ilhotas de Langerhans
Insulina
NADPH oxidase
NOX2
roGFP
Secreção de insulina
Abstract in Portuguese
O estresse oxidativo e a enzima NADPH oxidase-2 (NOX2) estão associados com a diminuição da massa funcional de células-β em pacientes com diabetes do tipo 2 (DT2). Neste estudo, testamos o papel da NOX2 sobre a glicotoxicidade em células-β. Ilhotas de camundongo C57BL/6J nocautes ou não para NOX2 (NOX2-KO e WT, respectivamente) foram isoladas e cultivadas por até 3 semanas em 10 ou 30 mmol/l de glucose (G10 e G30, respectivamente). A secreção de insulina foi maior nas ilhotas NOX2-KO vs. WT sem apresentar diferenças metabólicas ou do potencial redox da glutationa citosólica (EGSH). O cultivo de ilhotas em G30 aumenta a concentração de H2O2 e a oxidação de tióis no compartimento citosólico, seguido por aumento de apoptose de células-β, mas, preservando a reposta máxima secretória. Estas respostas foram quase idênticas em ambos os tipos de ilhotas. Em conclusão, a NOX2 regula negativamente a secreção de insulina em ilhotas de camundongos C57BL/6J, mas não é um componente crítico para a sobrevivência de células β em um modelo in vitro de glicotoxicidade.
Title in English
Redox modulation, function and survival of pancreatic β-cells: evidence on the role of NADPH oxidase-2 (NOX2) enzyme in a model of glucotoxicity in vitro.
Keywords in English
β-cell
Apoptosis
Insulin
Insulin secretion
Islets of Langerhans
NADPH oxidase
NOX2
roGFP
Abstract in English
Oxidative stress and NADPH oxidase-2 (NOX2) enzyme are associated to the decline of the functional β-cell mass in type 2 diabetes (T2D). Here, we tested the role of NOX2 on β-cell glucotoxicity. NOX2 knockout (NOX2 KO) and wild type (WT) C57BL/6J mice islets were isolated and cultured up to 3 weeks at 10 or 30 mmol/l glucose concentrations (G10 and G30, respectively). The insulin secretion was higher in NOX2-KO vs. WT islets despite similar metabolic and cytosolic glutathione-redox potential (EGSH) changes. The prolonged culture at G30 increases the H2O2 concentration and cytosolic thiol oxidation, followed by increased βcell apoptosis but preserving maximal secretory response. These responses were almost identical in both types of islets. In conclusion, NOX2 is a negative regulator of insulin secretion in C57BL/6J mouse islets, but is not a critical component for β-cell survival in a model of glucotoxicity in vitro.
 
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Release Date
2018-09-06
Publishing Date
2016-09-06
 
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