Endocrine pancreas plasticity of mice offspring after maternal treatment with glucocorticoid during late gestation

Abstract

The pancreatic ² cells have ample capacity to adapt to numerous physiological demands via cellular processes of proliferation, transdifferentiation, hypertrophy and apoptosis. The neonatal period is a stage of high plasticity of the endocrine pancreas, however the mechanisms involved in this process are not fully understood. The hepatocyte nuclear factor 4± (HNF4±) is a transcription factor involved in the regulation of glucose-stimulated insulin secretion and proliferation of pancreatic cells. Thus, HNF4± may be involved in the plasticity of the endocrine pancreas. Epigenetic studies have investigated the impact of exposure to glucocorticoids (GC) during intrauterine period on the endocrine pancreas development and point to glucose intolerance as a metabolic outcome in adult offspring. During the early postnatal period there is high cell plasticity and the endocrine pancreas of rodents are able to recover the ² cell mass after neonatal insult. Thus, we hypothesize that the ability of the endocrine pancreas to recover the ² cell mass after exposure to streptozotocin will be reduced in the adult offspring of mice exposed to GC in late gestation. With this strategy to promote reduction in ² cells mass in newborn animals, in which cell plasticity is quite pronounced, we will investigate the main molecular targets involved in the plasticity of ² cells and how vulnerable they are in offspring exposed to GC in critical periods of development. For this, we will monitor ² and ± cells mass throughout growth up to adult period and evaluate gene expression and methylation profile of the main transcription factors involved in the development of the endocrine pancreas, as well as the involvement of HNF4-± in the cell growth process through the use of ±-HNF4 -/- animals. (AU)