Estrogen attenuates AGTR1 expression to reduce pancreatic β-cell death from high glucose

Chronic exposure of pancreatic β-cells to high glucose levels results in β-cell dysfunction and death. These effects can be protected by estrogen. The local pancreatic renin-angiotensin system (RAS) has been shown as a novel pathological pathway of high-glucose-induced cell death. The effect of estrogen on pancreatic RAS is still unknown. This study examines whether estrogen protects against pancreatic β-cell death caused by glucotoxicity via a decrease in the pancreatic β-cell RAS pathway. When INS-1 cells were cultured in a high glucose medium, cell death was significantly higher than when the cells were cultured in a basal glucose medium; similarly, there were also higher levels of AGTR1 and p47 (ph) ° (x) mRNA, and protein expression. Moreover, the addition of 10(−8) M 17β-estradiol to INS-1 cells cultured in a high glucose medium markedly reduced cell death, AGTR1 and p47 (ph) ° (x) mRNA levels, and protein expression. Similar results were demonstrated in the pancreatic islets. The presence of 10(−8) M 17β-estradiol, losartan, or a combination of both, in a high glucose medium had similar levels of reduction of p47 (ph) ° (x) mRNA and protein expression, compared with those cultured in high glucose. Taken together, estrogen protected pancreatic β-cells from high-glucose-induced cell death by reducing the AGTR1 pathway.