Identificação de miRNAs desregulados envolvidos na disfunção das células ²- pancreáticas de ratas com hiperglicemia programada pelo diabete materno

• Grant number: 24/11596-6
• Support Opportunities: Scholarships in Brazil - Support Program for Fixating Young Doctors
• Start date: July 01, 2024
• End date: June 30, 2025
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Agreement: CNPq
• Principal Investigator: Débora Cristina Damasceno
• Grantee: Verônyca Gonçalves Paula
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated research grant: 24/02138-4 - miRNAs involved in the dysfunction of pancreatic ²-cells in rats with hyperglycemia programmed by maternal diabetes, AP.R

Abstract

Diabetes mellitus (DM) is a growing epidemic worldwide due to a multifactorial combination of genetic andenvironmental factors. Type 2 Diabetes mellitus (DM2), with greater prevalence, increases the risk ofmultiple diseases and its etiology combines insulin resistance and/or deficiency in insulin secretion,together with pancreatic ²-cell failure. Research based on genome sequencing has found changes in genesimportant for the development, maturation and function of ² cells, which may be associated with the risk ofdeveloping diabetes, and these mechanisms involve epigenetic control mediated by microRNAs (miRNAs).Important miRNAs for the ² cell were identified, such as miR-7, miR-199a-3p, miR-342, miR-17, miR-338-3p, miR-9, and miR-29, among others, being identified as possible biomarkers of DM2 and possibletherapeutic targets of the disease. Intrauterine exposure to diabetes can affect fetal development, leadingto long-term effects on the health of the offspring and it is known that miRNA can cross the placentalmembrane and thus participate in the regulation of several fetal systems, including pancreaticdevelopment. Therefore, it is important to understand whether deregulated miRNAs involved in ²-cellfunction may be related to pancreatic changes in the offspring of diabetic mothers and whether they canbe considered biomarkers for the study and understanding of the intergenerational passage of the diabeticphenotype. Therefore, the present project aims to evaluate the impact of maternal hyperglycemia on theexpression of deregulated miRNAs in pancreatic islets isolated from diabetic rat and their female offspringin adulthood, which are related to the function of the pancreatic ² cell. Female Sprague Dawley rats withdiabetes and their daughters will be used, as well as non-diabetic rats (control) as a comparative group. Inthe adult life (120 days of life) of these rats, laparotomy will be performed to collect the pancreas andisolate the pancreatic islets that will be processed for subsequent transcriptomic analysis and identificationof the miRNAs involved in the function of the pancreatic ² cell, which can be important predictivebiomarkers. of the passage of the diabetic phenotype to the offspring. By identifying the profile ofderegulated miRNAs in diabetic mother rats and their daughters, we will be able to better understand thecomplex role of these miRNAs in the passage of the diabetic phenotype between generations, as well asdirect new research and identify targets for new therapeutic opportunities. (AU)