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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2015.tde-02062015-095423
Document
Author
Full name
Patricia Rodrigues Lourenço Gomes
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2015
Supervisor
Committee
Silva, Silvana Auxiliadora Bordin da (President)
Carpinelli, Angelo Rafael
Cecatti, José Guilherme
Donato Júnior, José
Heimann, Joel Claudio
Title in Portuguese
Efeito da exposição à dexametasona sobre a expressão de miRNA no pâncreas endócrino e a homeostasia glicêmica de ratas prenhes.
Keywords in Portuguese
Célula beta
Gestação
Glicocorticoide
Homeostasia glicêmica
miRNA
Abstract in Portuguese
Este estudo investigou se o tratamento com glicocorticoide durante a gestação altera o metabolismo energético, hormonal e molecular materno, a função das ilhotas pancreáticas e mudanças correlativas sobre miRNAs. Foram utilizadas 80 ratas dividas em dois grupos de 40 animais, sendo um grupo destinado para envelhecimento até um ano após o desmame da prole, e o seguinte grupo destinado para experimentação no 20º dia de gestação, ambos dispostos em: CTL - controle, CTL-Dex - controle tratadas com dexametasona por 6 dias, P - prenhes e P-Dex - prenhes tratadas com dexametasona do 14º-19º dia de gestação. A expressão de miRNA das ilhotas foram analisadas em larga escala. Os genes alvos foram rastreados em banco de dados e confirmados. Por fim, investigou-se o mecanismo de modulação da homeostasia glicêmica. Inúmeras modificações resultaram da terapia com DEXA na gestação concluindo que a associação do tratamento ao período gravídico modula positivamente membros da família miRNA-29 ocasionando um desequilíbrio na homeostasia glicêmica por meio de falha na maquinaria exocitótica em longo prazo, desencadeado pela modulação negativa de progesterona e seu receptor promovendo prejuízo no processo de remodelação da ilhota pancreática na fase final da gestação.
Title in English
Effect of exposure to dexamethasone on miRNA expression in the endocrine pancreas and glucose homeostasis of pregnant rats.
Keywords in English
Beta cell
Glucocorticoid
Glucose homeostasis
miRNA
Pregnancy
Abstract in English
This study investigated whether treatment with glucocorticoids during pregnancy alters the energetic, hormonal and molecular maternal metabolism, function of pancreatic islets and correlative changes of miRNAs. Were used 80 rats divided into two groups of 40 animals, one group designed to aging up one year after weaning, and the next group destined to experimentation at 20th day of gestation, both arranged: CTL - control, CTL-Dex - control treated with dexamethasone for 6 days, P - pregnant rats and P-Dex - pregnant rats treated with dexamethasone from 14th to 19th day of pregnancy. Pancreatic islets were collected for large-scale analysis of miRNA expression. The target genes were screened and confirmed by qPCR. Finally it was investigated the mechanism of modulation of glucose homeostasis through qPCR and Western Blot. We can be observed numerous changes resulting from therapy with DEXA in pregnancy concluded that the association of treatment to the pregnancy period modulates members of the miRNA-29 family causing an imbalance in glucose homeostasis through long-term failure in exocytotic machinery, triggered by the downregulation of the progesterone and its receptor promoting injury in the pancreatic islet remodeling process in late pregnancy.
 
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Publishing Date
2015-06-03
 
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