Mechanisms involved in the late-onset pancreatic beta cell disfunction induced by maternal glucocorticoid excess at the end of pregnancy

• Grant number: 14/08913-8
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2015
• End date: January 31, 2017
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Silvana Auxiliadora Bordin da Silva
• Grantee: Silvana Auxiliadora Bordin da Silva
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Camilo de Lellis Santos ; Gabriel Forato Anhê

Abstract

Pregnancy is a period of physiological insulin resistance, where the increase in both pancreatic beta cell mass and insulin secretory capacity preserves the maternal normoglycemia. After the gestational increase in the mass and activity, a rapid involution of the endocrine pancreas takes place in the beginning of post-partum period. This phenomenon constitutes one the mechanisms that avoid maternal post-partum hypoglycemia. During the last 12 years our group has been drawing up a molecular blueprint of the events involved in the maternal pancreatic islet remodeling in the peripartum period. We have described some mechanisms involved in the modulation of insulin secretion (Bordin et al., 2004; Anhê et al., 2006, 2007; Lellis-Santos et al., 2012) and in the beta cell mass resetting (Nicoletti-Carvalho et al., 2010; Bromati et al., 2011). More recently we have demonstrated that subtle functional changes induced by the excess of glucocorticoids at the end of pregnancy are associated with a late-onset impairment in insulin secretion and glucose intolerance (Gomes et al., 2014). Considering that the events involved in the beta cell remodeling must operate in a close time window to maintain the proper maternal energy metabolism, we hypothesized that metabolic or hormonal insults (such as the excess of glucocorticoids) could be disturbing the morpho-functional pancreatic resetting, thus resulting in the impairment of the secretory capacity later in life. Based on this premise the aims of this project are (i) to investigate the resetting profile and its mechanisms (apoptosis and cell proliferation) in islets of rats exposed to an excess of glucocorticoids in the last third of pregnancy. Pregnant Wistar rats will be treated with dexamethasone and used for functional (GTT, ITT, PTT, body composition), biochemical (random glycemia, cholesterol, triglycerides), and hormonal analyses (P4, E2, prolactin, leptin, insulin, corticosterone) during the peripartum period. Isolated pancreatic islets will be used to assess apoptosis (flow citometry, western blot) and cell proliferation (elisa, western blot), as well as the molecular mechanisms involved in the remodeling process (western blot, qPCR, ChIP assay). (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)

PAYOLLA, TANYARA B.; TEIXEIRA, CAIO J.; SATO, FABIO T.; MURATA, GILSON M.; ZONTA, GIZELA A.; SODRE, FRHANCIELLY S.; CAMPOS, CAROLINA V.; MESQUITA, FILIPHE N.; ANHE, GABRIEL F.; BORDIN, SILVANA. In Utero Dexamethasone Exposure Exacerbates Hepatic Steatosis in Rats That Consume Fructose During Adulthood. NUTRIENTS, v. 11, n. 9, SEP 2019. (13/07607-8, 14/08913-8, 15/25597-5)