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MicroRNAs in pancreatic islets as possible biomarkers for type 2 diabetes mellitus (T2DM): study on neonatal and adult phase of the offspring of diabetic rats

Grant number: 18/16402-4
Support type:Regular Research Grants
Duration: November 01, 2018 - October 31, 2020
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Aparecida Emiko Hirata
Grantee:Aparecida Emiko Hirata
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Assoc. researchers:Manoel de Arcisio Miranda Filho

Abstract

Diabetes mellitus type 2 (DM2) is the metabolic disease more prevalent throughout the world and is characterized by chronic hyperglycemia with disorder in the metabolism of carbohydrates, fats and proteins, resulting from defects in insulin secretion, action or both. The pathophysiology of DM2 has been primarily associated with the increase in inflammatory sub-clinic framework and development of peripheral resistance to insulin. Many evidences show that the fetal and neonatal, embryonic development is influenced by adverse factors that affect pregnant women and are associated with health conditions of individuals in adulthood. Studies have shown that the children of diabetic mothers are predisposed to obesity, glucose intolerance, insulin resistance and hypertension in adulthood. The presence of hyperglycemia during pregnancy appears to be responsible for defects in glucose metabolism and function of pancreatic ² cells of the offspring. Evidences suggest that a hostile intrauterine environment leads to changes in the expression and function of the genes in the offspring and this mechanism seems to involve the expression of microRNAs. In addition, several studies have shown that the deregulation of microRNAs contributes to the development of insulin resistance and the circulating microRNAs can be considered as biomarkers of diseases such as DM2. Thus, the present study will evaluate the impact of maternal hyperglycemia on the expression of miRNAs in pancreatic islets isolated from neonatal and adulthood offspring. For both female rats will be subjected to induction of diabetes through the administration of Streptozotocin (60 mg/kg ip) and after confirmation of diabetes will be mated. The offsprings will be studied at birth and at 3 months of age. The generation of reactive oxygen species and the insulin secretory process will also be assessed in the different phases of development. Therefore, our hypothesis is that the microRNAs can be important biomarkers predictors of DM2 in adult life of the offspring of diabetic mothers. (AU)