The Role Of Nuclear Receptor RXR Alpha In The Regulation Of Pancreatic Beta Cells Function

In recent years,diabetes has become one of the most serious and critical health problems in the world.There are three main types of diabetes,type 1 diabetes,type 2 diabetes and gestational diabetes.Type 2 diabetes is the most common type of diabetes,accounting for around 90%of all cases of diabetes.In type 2 diabetes,hyperglycaemia is the result of an inadequate production of insulin and inability of the body to respond fully to insulin,defined as insulin resistance.Retinol X receptor alpha(RXR alpha)is an important member of nuclear receptor superfamily.Studies have shown that RXR alpha extensively participates in almost all important cellular processes,such as cell proliferation,differentiation and apoptosis.Under different conditions,the up-regulation or down-regulation of RXR alpha expression indicates some abnormal changes in cells.Therefore,the ectopic expression of RXR alpha is closely related to some of the maj or diseases of human.In this study,zebrafish was used as model organism,and the nuclear receptor RXR alpha was used as the target gene.Pancreatic beta cells,which are crucial for the development and progression of diabetes mellitus,were taken as the object of study.The purpose of this study was to explore the role of nuclear receptor RXR alpha in the function and mass of pancreatic beta cells.It has been confirmed that there are significant differences in high-glucose-stimulated insulin secretion in RXR alpha knockout transgenic mice.On this basis,we generated a zebrafish mutant with RXR alpha knockout,and found that its free blood glucose level of RXRaa.-/-;RXRab-/-zebrafish decreased,its pancreatic beta cells increased.Further studies revealed that the increased number of pancreatic beta cells was not related of the self-replication of the existingpancreatic beta cells,and not from the differentiation of precursor/progenitor cells,and it was preliminarily determined that the increased pancreas beta cells may be derived from the transdifferentiation of other pancreatic cells.As the nuclear receptor RXR alpha often exists and plays a role in the form of homologous or heterodimer,we studied the nuclear receptor that interacts with RXR alpha in pancreatic beta cells.It was found that there is a strong interaction between RXR alpha and RAR alpha,suggesting that RAR alpha and RXR alpha may participate in the negative regulation of RXR alpha on the number of pancreatic beta cells.In summary,our study explored how nuclear receptor RXR alpha could play a negative regulatory role in pancreatic beta cells,these data provide some information for understanding of its roles in the prevention and treatment of diabetes mellitus.