Underlying molecular mechanisms in the glucocorticoid-induced inhibition of pancreatic beta cell proliferation.

Author(s)

José Edgar Nicoletti Carvalho

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2010-06-21

Examining board members

Silvana Auxiliadora Bordin da Silva; Gabriel Forato Anhê; Maria Lucia Cardillo Correa Giannella; Ubiratan Fabres Machado; Lício Augusto Velloso

• Advisor: Silvana Auxiliadora Bordin da Silva

Abstract

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. (AU)