Progesterone effect on the expression of genes involved in oxidative stress and antioxidant defense in pancreatic beta cells and the relationship between the redox state in the plasma of pregnant women and the development of gestational diabetes

Abstract

Gestational diabetes (DG) affects between 3 and 7% of pregnant women worldwide and is characterized by hyperglycemia starting in the second trimester of pregnancy. Evidence suggests that progesterone (PG) whose concentrations increase during pregnancy could contribute to the insufficient adaptation of the pancreatic ² cells mass. The PG has been related to DG in studies that have identified pro-oxidant action of this hormone and its involvement in apoptosis of certain cell types, although the pathways involved are not yet clear. Our group showed that PG induced death of pancreatic ² cells and that preincubation with ±-tocopherol attenuated or abolished this effect. This study aims to evaluate the effect of progesterone on the expression of genes involved in oxidative stress and antioxidant defense in pancreatic ² cells (RINm5F); also, we will investigate the presence of redox state markers in the plasma of pregnant women and its relationship to plasma progesterone concentrations and GD development. Gene expression analysis will be performed by PCR Array. Proteins encoded by the selected genes will be investigated by suitable strategies such as Western Blotting, ELISA and others. In the plasma of pregnant women, it will be determined the activity of SOD and CAT, and GSH and 4-hidroxy-2-nonenal contents. This project may contribute for the better understanding of the pathogenesis of DG, opening new perspectives for the development of strategies for prevention and treatment of the disease. (AU)