Metformin attenuates high glucose-induced injury in islet microvascular endothelial cells

As one of the most frequently prescribed antidiabetic drugs, metformin can lower glucose levels, improve insulin resistance manage body weight. However, the effect of metformin on islet microcirculation remains unclear. In the present study, to explore the effect of metformin on islet endothelial cells and investigated the underlying mechanism, we assessed the effects of metformin on islet endothelial cell survival, proliferation, oxidative stress and apoptosis. Our results suggest that metformin stimulates the proliferation of pancreatic islet endothelial cells and inhibits the apoptosis and oxidative stress caused by high glucose levels. By activating farnesoid X receptor (FXR), metformin increases the expression of vascular endothelial growth factor-A (VEGF-A) and endothelial nitric oxide synthase (eNOS), improves the production of nitric oxide (NO) and decreases the production of ROS. After the inhibition of FXR or VEGF-A, all of the effects disappeared. Thus, metformin appears to regulate islet microvascular endothelial cell (IMEC) proliferation, apoptosis and oxidative stress by activating the FXR/VEGF-A/eNOS pathway. These findings provide a new mechanism underlying the islet-protective effect of metformin.