Metformin Prevented High Glucose-induced Endothelial Reactive Oxygen Species Via OGG1 in an AMPKα-Lin-28 Dependent Pathway

Aims: Metformin improves vascular function in obese type 2 diabetic patients. 8-Oxoguanine glycosylase (OGG1) is a main DNA glycosylase that is involved in vascular complications in various diseases. However, whether metformin suppresses endothelial reactive species oxygen production via the OGG1 pathway is unclear.

Main Methods: Human umbilical vein endothelial cells (HUVECs) were exposed to HG (high glucose) with or without metformin. OGG1 and AMPKα levels were measured after metformin treatment, while HG-induced ROS were measured by a DHE probe.

Key Findings: Metformin reduced HG-induced endothelial ROS by upregulating OGG1. Additionally, OGG1 protein expression was dependent on its mRNA stability, which was reversed by genetic inhibition of AMPKα and Lin-28. Furthermore, the effect of OGG1 on HG-induced ROS was partially dependent on the AHR/Nrf2 pathway in HUVECs.

Significance: These results suggested that metformin modulated HG-induced endothelial ROS via the AMPKα/Lin-28/OGG1 pathway.