Investigation on epigenetic mechanisms involved in islet dysfunction by prenatal glucocorticoid treatment

• Grant number: 19/10543-8
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: October 01, 2019
• End date: September 30, 2020
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Antonio Carlos Boschiero
• Grantee: Cristiane dos Santos
• Supervisor: Charlotte Ling
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: Lund University, Malmö, Sweden
• Associated to the scholarship: 16/23140-0 - Endocrine pancreas plasticity of mice offspring after maternal treatment with glucocorticoid during late gestation, BP.DR

Abstract

The pancreatic beta-cell dysfunction plays an important role on the development of type 2diabetes (DM2), and it is know that genetic and epigenetic factors contribute to the susceptibility of this disease. Epidemiological evidences suggest that exposure to an adverse environment, in early life, is associated with an increased risk of metabolic disorders in adulthood. Overexposure to glucocorticoids (GC), during fetal period of life, is one important factor that impacts the development promoting glucose intolerance in adult offspring, probably by epigenetic mechanisms, which are not fully understood. Considering that genetic predisposition and environmental factors are involved with the development of DM2, and that intrauterine exposure to excess GC impairs the offspring's pancreas function (turning them more susceptible to DM2), our objective is to assess the epigenetic mechanisms involved with this beta-cell failure. For this, we will analyze the genone-wide DNA methylation and gene expression profile of islet from offspring exposed to prenatal GC. Besides that, we propose to evaluate the effect of GC on human islets and beta-cell function. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DOS SANTOS, CRISTIANE; KARAGIANNOPOULOS, ALEXANDROS; RAFACHO, ALEX; PERFILYEV, ALEXANDER; ELIASSON, LENA; LING, CHARLOTTE; BACOS, KARL. Glucocorticoids and glucolipotoxicity alter the DNA methylome and function of human EndoC-beta H1 cells. Life Sciences, v. 307, p. 10-pg., 2022-08-09. (19/10543-8)

DOS SANTOS, CRISTIANE; RAFACHO, ALEX; FERREIRA, SANDRA MARA; VETTORAZZI, JEAN FRANCIESCO; DOS REIS ARAUJO, THIAGO; MATEUS GONCALVES, LUCIANA; RUHRMANN, SABRINA; BACOS, KARL; LING, CHARLOTTE; BOSCHERO, ANTONIO CARLOS; et al. Excess of glucocorticoids during late gestation impairs the recovery of offspring's beta-cell function after a postnatal injury. FASEB JOURNAL, v. 35, n. 8, AUG 2021. (19/10543-8, 16/23140-0, 15/12611-0)