Figure 2.

Mechanism of high glucose-induced cellular events in cancer cells. High glucose (hyperglycemia) generates cellular ROS mainly through mitochondrial metabolism; elevated ROS activate MAPK cascade, which cause cellular events by inducing related genes transcription. In addition, high glucose can induce activation of protein kinase C (PKC) through direct and indirect pathways. It is also speculated that high glucose may induce EGF transcription and EGFR transactivation, contributing to various biological behavior of cancer cells. High glucose-mediated GDNF upregulation may also involve in different cellular events through GDNF/RET cascade.