Role Of Transcription Factor Ets1in Insulin Secretion And Proliferation Of Pancreatic β-cells

Objective:This thesis was aimed to investigate the role and mechanism of Ets1in insulin secretion and proliferation of pancreatic β-cells.Methods:Immunofluorescence analysis was carried out to determine the expression and localization of Ets1in the mouse pancreas, and immunohistochemistry was performed to compare Ets1phosphorylation level in the islets between Chow and HFD fed mice. Insulin concentration was measured by Elisa analysis in the culture media of isolated islets overexpressing Ets1. cDNA microarray revealed the target gene of Ets1in Min6cells, and the result was confirmed in both Min6cells and isolated mouse islets by western blot and qRT-PCR respectively. In contrast, the gene’s expression was detected by western blot when Ets1was inhibited by siRNA in Min6cells. CHIP and luciferase assay were used to explore the underlying mechanism on how Ets1regulates its expression in Min6cells. The role of Ets1in Min6cell proliferation was determined by using EdU staining and MTT assay.Results:Etsl was mainly expressed in P-cells rather than a-cells in the mouse pancreas. Compared with Chow fed mice, Ets1phosphorylation was significantly induced in the islets of HFD fed mice and the phosphorylation of Ets1was induced by high glucose concentration in Min6cells. Overexpression of Ets1inhibited glucose-stimulated insulin secretion. The expression of Txnip was induced by Etsl overexpression in Min6cells and isolated islets. Conversely, inhibition of Etsl by siRNA reduced Txnip expression in Min6cells. Ets1directly bound to Txnip gene promoter and acted with p300synergistically to activate Txnip promoter reporter. Etsl overexpression significantly inhibited the proliferation of Min6cells and stimulated p21expression.Conclusions:Transcription factor Ets1inhibits glucose-stimulated insulin secretion and proliferation by inducing Txnip and p21expression, respectively, in pancreatic β-cells.