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Doctoral Thesis
DOI
10.11606/T.42.2010.tde-11082010-133105
Document
Author
Full name
José Edgar Nicoletti Carvalho
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2010
Supervisor
Committee
Silva, Silvana Auxiliadora Bordin da (President)
Anhê, Gabriel Forato
Giannella, Maria Lucia Cardillo Correa
Machado, Ubiratan Fabres
Velloso, Lício Augusto
Title in Portuguese
Mecanismos moleculares envolvidos na redução da proliferação de células beta pancreáticas induzida por glicocorticóides.
Keywords in Portuguese
Diabetes mellitus
Biologia molecular
Glicocorticóides
Gravidez
Ilhotas de Langerhans
Lactação animal
Abstract in Portuguese
Durante a gravidez, o pâncreas endócrino materno sofre alterações morfológicas e funcionais que resultam no aumento da massa de células beta e da secreção de insulina. Nos estágios finais da gestação ocorre aumento dos níveis plasmáticos de glicocorticóides que resulta na diminuição da secreção e da proliferação das células beta. Este fenômeno, que ocorre no período compreendido entre o final da gravidez e o inicio da lactação, promove a reversão fisiológica da adaptação funcional que se fez necessária durante a gravidez. Assim, estudamos mecanismos moleculares envolvidos na redução de proliferação destas células. As proteínas cinases reguladas por sinais extracelulares (ERK) estão envolvidas no crescimento e sobrevida celular. Os resultados mostram que o glicocorticóide sintético, dexametasona, diminui a proliferação de células beta e, para isto, induz diminuição da fosforilação das ERK-1/2 por meio do aumento da expressão de uma fosfatase de MAPK (MKP-1). Este mecanismo deve estar envolvido no remodelamento pancreático pós-natal induzido pelos glicocorticóides.
Title in English
Underlying molecular mechanisms in the glucocorticoid-induced inhibition of pancreatic beta cell proliferation.
Keywords in English
Diabetes mellitus
Animal Lactation
Glucocorticoid
Islets of Langerhans
Molecular biology
Pregnancy
Abstract in English
During pregnancy, maternal pancreatic islets undergo morphofunctional changes that increase beta cell mass and insulin secretion. At late stages of pregnancy there is an increase in plasma glucocorticoid levels that inhibit beta cell proliferation and beta cell function. This situation, which occurs in a period between late pregnancy and early stages of lactation, counteracts the functional gain established throughout pregnancy. In this work we studied the molecular mechanisms involved in the impaired beta cell proliferation. The extracellular regulated kinases (ERKs) are involved in cellular growth and survival. Our results show that dexametasone, a synthetic glucocorticoid, inhibits proliferation by a mechanism that includes up regulation of a dual specificity phosphatase (MKP1). This, by extension, impairs ERK1/2 activation. This mechanism could take part in the induced-glucocorticoid reestablishment of endocrine pancreatic mass after parturition.
 
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Publishing Date
2010-09-08
 
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