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Endocrine pancreas maturation and differentiation in offspring of females submitted to dexamethasone treatment during pregnancy

Grant number: 15/23285-6
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): January 01, 2016
Effective date (End): February 28, 2019
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Silvana Auxiliadora Bordin da Silva
Grantee:Junia Carolina Rebelo dos Santos Silva
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID

Abstract

The restriction of intrauterine growth resulting in low birth weight, is considered an important risk factor for the later development of metabolic diseases. Several epidemiological studies have shown a link between low birth weight susceptibility to developing type 2 diabetes, hypertension, cardiovascular disease and obesity later in life. Various models are used for the study of intrauterine growth restriction, such as calorie restriction, malnutrition and the use of glucocorticoids. In our laboratory we use the model of administration of dexamethasone in the drinking water because of the high reproducibility of biological effects and, more importantly, it is a common feature of several metabolic insults, such as protein energy malnutrition, stress and obesity. In rats, administration of dexamethasone during pregnancy leads to reduced birth weight and results in impaired glucose tolerance and obesity in adult life of the offspring. Although insulin is expressed in pancreatic beta cells from fetuses between the 8th and 9th week of gestation in humans and in mice 13.5 days, maturation of the secretory capacity occurs only a few days after birth. Evidence shows that during the fetal stage and the early stages of neonatal life, insulin secretory response to glucose and Ca2+ influx are deficient compared to those observed in adulthood. Still, the biphasic pattern of secretion is not found in the perinatal period. These features only come to be observed from the 3rd day after birth. The mechanisms involved in the insulin secretory response maturation process triggered during development are relatively well known. The role of some transcription factors involved in beta-cell maturation in pre- and post-natal period, as Ngn3, PDX-1, Nkx6.1, Nkx2.2 and MafA and its regulation by microRNAs have been identified. Despite of these finding, there are no reports on the influence of prenatal glucocorticoid excess on the coordinated action of these transcription factors in pancreatic maturation. (AU)

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