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Doctoral Thesis
DOI
10.11606/T.42.2016.tde-17022016-152108
Document
Author
Full name
Daniel Simões de Jesus
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2015
Supervisor
Committee
Carpinelli, Angelo Rafael (President)
Curi, Rui
Garcia, Rodrigo Antonio Peliciari
Laurindo, Francisco Rafael Martins
Lopes, Lucia Rossetti
Title in Portuguese
A desregulação dos genes relógio modifica o estado redox das células β pancreáticas e modula a secreção de insulina estimulada pela glicose via NADPH oxidase.
Keywords in Portuguese
EROs
Genes relógio
NADPH oxidase
Secreção de insulina
Abstract in Portuguese
Os genes relógio são responsáveis pelo ritmo circadiano e homeostase de diversos sistemas biológicos, incluindo o pâncreas endócrino. Nas células β são de grande importância para a regulação do metabolismo e da secreção de insulina (SI), e sua ausência pode levar ao desenvolvimento do diabetes. A NADPH oxidase (NOX) é um complexo enzimático responsável pela produção do ânion superóxido através da redução do oxigênio molecular. Em ilhotas pancreáticas, a NOX participa da regulação do metabolismo da glicose e da SI, através da modulação do estado redox intracelular. O objetivo do nosso estudo foi verificar se a desregulação dos genes relógio mediada pela ausência de Bmal1 seria capaz de modular a NOX e o estado redox nas células β pancreáticas, influenciando assim a SI. Observamos que a ausência de Bmal1 alterou a atividade e expressão da NOX, desregulando o estado redox intracelular. Essas alterações levaram à redução da viabilidade celular e mudanças na resposta à estimulação com glicose, resultando em uma deficiência na principal função da célula β a SI.
Title in English
Clock genes dysregulation modifies the redox state of pancreatic β cell and modulates glucose stimulated insulin secretion via NADPH oxidase.
Keywords in English
Clock genes
Insulin secretion
NADPH oxidase
ROS
Abstract in English
Clock genes are responsible for homeostasis and circadian rhythm in various biological systems, including endocrine pancreas. In β -cells, they are important for the regulation of metabolism and insulin secretion (IS), and its absence can lead to development of diabetes. NADPH oxidase (NOX) is an enzymatic complex responsible for production of superoxide anion by reducing molecular oxygen. In pancreatic islets, NOX regulates glucose metabolism and IS through modulation of the intracellular redox state. The aim of our study was to investigate whether dysregulation of clock genes mediated by Bmal1 suppression would be able to modulate NOX activity and redox state in pancreatic β cells, thus influencing the SI. In this work, the lack of Bmal1 altered the activity and expression of NOX, deregulating the intracellular redox state. These changes led to reduced cell viability and changes in cell response after stimulation with glucose, resulting in a deficiency in β cell main function, GSIS.
 
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Release Date
2018-02-16
Publishing Date
2016-02-17
 
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