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Doctoral Thesis
DOI
10.11606/T.42.2007.tde-28012008-110034
Document
Author
Full name
Daniela Morgan Mendes
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2007
Supervisor
Committee
Carpinelli, Angelo Rafael (President)
Carneiro, Everardo Magalhães
Carvalho, Carla Roberta de Oliveira
Hirata, Aparecida Emiko
Silva, Silvana Auxiliadora Bordin da
Title in Portuguese
Modulação da enzima NAD(P)H oxidase pela glicose, palmitato e interleucina - 1? e sua participação no processo de secreção de insulina induzido pela glicose.
Keywords in Portuguese
Glicose
Ilhotas pancreáticas
Interleucina.
NAD(P)H oxidase
Palmitato
Secreção de insulina
Abstract in Portuguese
Neste projeto, demonstramos a modulação da enzima NAD(P)H oxidase pela glicose, palmitato e interleucina - 1? através da análise da expressão protéica do componente p47PHOX e pela atividade dessa enzima via produção de superóxido e peróxido de hidrogênio. Demonstramos também a participação da enzima NAD(P)H oxidase no processo de secreção de insulina induzido pela glicose pois a inibição da enzima pelo DPI e oligonucleotídeo anti p47PHOX promoveu uma diminuição da secreção do hormônio. A partir desse dado passamos a avaliar o mecanismo de ação da enzima no processo secretório e demonstramos que a inibição dessa enzima promove uma inibição de genes essenciais no processo de secreção de insulina como GLUT-2 e glicocinase.Assim podemos concluir que a enzima NAD(P)H oxidase é modulada pela glicose, palmitato e interleucina 1? e que essa enzima participa do processo de secreção insulina modulando genes essenciais para o processo secretório como GLUT-2 e glicocinase.
Title in English
NAD(P)H oxidase modulation by glucose, palmitate and interleukin 1? and the participation on the process of glucose-induced insulin secretion.
Keywords in English
Glucose
insulin secretion
Interleukin
NAD(P)H oxidase
Palmitate
Pancreatic islets
Abstract in English
The expression and activity of the componenents of NAD(P)H oxidase in pancreatic islets were described for the first time in our laboratory (OLIVEIRA, HR et ai, 2003). It was shown the gene and protein expression of the components of this enzyme in Seta cells and that enzyme activation is mediated by glucose. Glucose induced insulin secretion was followed by increase in EROS generation and this increase was in part mediated by NAD(P)H oxidase activation (the same mechanism observed in phagocytes). In this study, the modulation of NAD(P)H oxidase activity by glucose, palmitate and interleukin 1ß as investigated through protein expression of p47phox vity of this enzyme through superoxide and hydrogen peroxide production. To determinate the role of NAD(P)H oxidase in the process of glucoseinduced insulin secretion the enzyme was inhibited by DPI and oligonucleotide anti p47phox, in the both cases the enzyme inhibition produced a decrease on insulin secretion. In order to investigated NAD(P)H oxidase mechanism of action in insulin secretion, we shown that the inhibition enzyme by DPI reduced the GLUT-2 and glucokinase gene expression. We can concluded hat NAD(P)H oxidase was modulated by glucose, palmitate and interleukin 1ß and that enzyme participed in process of glucoseinduced insulin secretion through modulation of GLUT-2 and glucokinase gene expression.
 
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Publishing Date
2008-06-10
 
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