miRNAs involved in the dysfunction of pancreatic ²-cells in rats with hyperglycemia programmed by maternal diabetes

• Grant number: 24/02138-4
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2024
• End date: June 30, 2026
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Agreement: CNPq
• Principal Investigator: Débora Cristina Damasceno
• Grantee: Débora Cristina Damasceno
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• City of the host institution: Botucatu
• Associated research grant: 23/04866-4 - Transcriptome determination of the pancreatic islets from rats with maternal Diabetes-programmed Hyperglycemia, AP.R
• Associated scholarship(s): 24/11596-6 - Identificação de miRNAs desregulados envolvidos na disfunção das células ²- pancreáticas de ratas com hiperglicemia programada pelo diabete materno, BP.JD

Abstract

Diabetes mellitus (DM) is a growing epidemic worldwide due to a multifactorial combination of genetic and environmental factors. Type 2 Diabetes mellitus (DM2), with greater prevalence, increases the risk of multiple 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 genes important for the development, maturation and function of ² cells, which may be associated with the risk of developing 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 possible therapeutic targets of the disease. Intrauterine exposure to diabetes can affect fetal development, leading to long-term effects on the health of the offspring and it is known that miRNA can cross the placental membrane and thus participate in the regulation of several fetal systems, including pancreatic development. Therefore, it is important to understand whether deregulated miRNAs involved in ²-cell function may be related to pancreatic changes in the offspring of diabetic mothers and whether they can be considered biomarkers for the study and understanding of the intergenerational passage of the diabetic phenotype. Therefore, the present project aims to evaluate the impact of maternal hyperglycemia on the expression of deregulated miRNAs in pancreatic islets isolated from diabetic rat and their female offspring in adulthood, which are related to the function of the pancreatic ² cell. Female Sprague Dawley rats with diabetes and their daughters will be used, as well as non-diabetic rats (control) as a comparative group. In the adult life (120 days of life) of these rats, laparotomy will be performed to collect the pancreas and isolate the pancreatic islets that will be processed for subsequent transcriptomic analysis and identification of the miRNAs involved in the function of the pancreatic ² cell, which can be important predictive biomarkers. of the passage of the diabetic phenotype to the offspring. By identifying the profile of deregulated miRNAs in diabetic mother rats and their daughters, we will be able to better understand the complex role of these miRNAs in the passage of the diabetic phenotype between generations, as well as direct new research and identify targets for new therapeutic opportunities. (AU)