IGF-1 Via PI3K/Akt/S6K Signaling Pathway Protects DRG Neurons with High Glucose-induced Toxicity

Hyperglycemia-induced toxicity of neurons contributes to the pathogenesis and progression of diabetic neuropathy (DNP). High concentration glucose triggered reactive oxygen species (ROS) overproduction and induced cell apoptosis of neurons from dorsal root ganglion (DRG) in vitro. Currently, there is no effective therapeutic method to retard this devastating complication or neurotoxicity induced by high glucose. Insulin-like growth factor-1 (IGF-1) has multi-neurotrophic actions which need to be explored regarding its actions and mechanisms on relieving high glucose induced neurotoxicity. Herein, high concentration glucose was exposed to the DRG neurons in vitro. The effects of IGF-1 on relieving high glucose-induced neurotoxicity were evaluated. We illustrated that IGF-1 enhanced regeneration of neurites sent from DRG neuronal cell bodies and increased neuronal viability which inhibited by high glucose challenge. IGF-1 alleviated neuronal apoptosis caused by high glucose exposure. IGF-1 also suppressed the intracellular ROS overproduction and ATF3 expression upregulation which was induced by high glucose insult. The anti-neurotoxic effects of IGF-1 might be through restoration of prosurvival PI3K/Akt/S6K signaling. These data shed some light on the treatment of intractable DNP and suggested that IGF-1 might be a potential effective agent on relieving high glucose induced neurotoxicity.