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

ABSTRACT: Chronic exposure of pancreatic ?-cells to high glucose levels results in ?-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 ?-cell death caused by glucotoxicity via a decrease in the pancreatic ?-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 17?-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 17?-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 ?-cells from high-glucose-induced cell death by reducing the AGTR1 pathway.

SUBMITTER: Kooptiwut S 

PROVIDER: S-EPMC5709427 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature