Identification And Phenotype Research Of Transgenic Mice Overexpressing Transcription Factor Ets-1 In Pancreatic ? Cells

Pancreatic islet ? cells are unique cell clusters which secrete insulin to maintain the plasma glucose levels in a strict physiological range. Diabetes occurs when either P cell function is impaired or ? cell mass reduced. Transcription factor Ets-1 belongs to the Ets family, which is involved in the lymphocyte development, and it is also associated with tumor metastasis and apoptosis by directly regulating MMPs, Pim-3, Caspase 1 and other genes expression. In addition, Ets-1 is associated with the complication of diabetes. Previous studies in our lab had showed that, Ets-1 could impair insulin biosynthesis and secretion via PDX-1 regulation. Moreover, Ets-1 could bind to the insulin gene promoter and directly down-regulate the expression of insulin. Since previous studies were performed in pancreatic (3 cells and primary islets, we generated transgenic mice specific overexpressing Ets-1 in ? cells under control of the rat insulin ? promoter in order to further study the effect of Ets-1 in vivo. After detecting the phenotype of mice, we got the gene copies stable genetic transgenic mice with Ets-1 expression by using relative and absolute quantification. Furthermore, we acquired the transgenic mice expressing Ets-1 mRNA at different levels, and the Ets-1 protein expression was consistent with mRNA results. Then the location of Ets-1 in pancreatic ? cells was further confirmed by using immunofluorescence. Intraperitoneal injection glucose tolerance test (IPGTT) results suggested that, transgenic mice had obvious impaired glucose tolerance and defected insulin secretion versus wild-type littermates, and the extent was positively correlated with Ets-1 expression. However, no significant difference was observed in insulin tolerance test. Moreover, impaired glucose-stimulated insulin secretions (GSIS), as well as decreased insulin content were observed in primary islets isolated from transgenic mice compared with wild-type littermates.In conclusion, our research suggests that, specific overexpressing Ets-1 in pancreatic ? cells in vivo, the mice develops glucose intolerance, insulin secretion deficiency, and the islet dysfunction. Our findings contribute a model to the understanding of P-cell function induced by transcription factor Ets-1 in the development of diabetes and provide potential new clues for the prevention and therapy of diabetes.