SDF-1 inhibits the dedifferentiation of islet β cells in hyperglycaemia by up-regulating FoxO1 via binding to CXCR4

Abstract

Islet β cell dedifferentiation is one of the most important mechanisms in the occurrence and development of diabetes. We studied the possible effects of chemokine stromal cell-derived factor-1 (SDF-1) in the dedifferentiation of islet β cells. It was noted that the number of dedifferentiated islet β cells and the expression of SDF-1 in pancreatic tissues significantly increased with diabetes. In islet β cell experiments, inhibition of SDF-1 expression resulted in an increase in the number of dedifferentiated cells, while overexpression of SDF-1 resulted in a decrease. This seemed to be contradicted by the effect of diabetes on the expression of SDF-1 in pancreatic tissue, but it was concluded that this may be related to the loss of SDF-1 activity. SDF-1 binds to CXCR4 to form a complex, which activates and phosphorylates AKT, subsequently increases the expression of forkhead box O1 (FOXO1), and inhibits the dedifferentiation of islet β cells. This suggests that SDF-1 may be a novel target in the treatment of diabetes.