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Dissecting the role of glucocorticoids on pancreas development

Gesina, Emilie
Tronche, Francois
Duchene, Belinda
Tales, Willemene
Czernichow, Paul
Breant, Bernadette
Published in Diabetes. 2004, vol. 53, no. 9, p. 2322-2329
Abstract To determine whether glucocorticoids are involved in pancreas development, glucocorticoid treatment of rat pancreatic buds in vitro was combined with the analysis of transgenic mice lacking the glucocorticoid receptor (GR) in specific pancreatic cells. In vitro treatment of embryonic pancreata with dexamethasone, a glucocorticoid agonist, induced a decrease of insulin-expressing cell numbers and a doubling of acinar cell area, indicating that glucocorticoids favored acinar differentiation; in line with this, expression of Pdx-1, Pax-6, and Nkx6.1 was downregulated, whereas the mRNA levels of Ptf1-p48 and Hes-1 were increased. The selective inactivation of the GR gene in insulin-expressing beta-cells in mice (using a RIP-Cre transgene) had no measurable consequences on beta- or alpha-cell mass, whereas the absence of GR in the expression domain of Pdx-1 (Pdx-Cre transgene) led to a twofold increased beta-cell mass, with increased islet numbers and size but normal alpha-cell mass in adults. These results demonstrate that glucocorticoids play an important role in pancreatic beta-cell lineage, acting before hormone gene expression onset and possibly also modulating the balance between endocrine and exocrine cell differentiation.
Keywords AnimalsCell DifferentiationCell Lineage/drug effectsDexamethasone/ pharmacologyEpithelial Cells/cytology/drug effects/physiologyEye ProteinsFemaleGlucocorticoids/ pharmacologyHomeodomain Proteins/geneticsInsulin/geneticsIslets of Langerhans/cytology/ embryology/physiologyMiceMice, Inbred C57BLPaired Box Transcription FactorsPancreas/cytology/ embryology/physiologyPregnancyRatsRats, WistarRepressor ProteinsStem Cells/cytology/drug effects/physiologyTrans-Activators/genetics
PMID: 15331541
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Research group Types cellulaires pancréatiques pendant l'ontogénèse (522)
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GESINA, Emilie et al. Dissecting the role of glucocorticoids on pancreas development. In: Diabetes, 2004, vol. 53, n° 9, p. 2322-2329. https://archive-ouverte.unige.ch/unige:8755

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Deposited on : 2010-07-12

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