Restoration of Autophagy in Hyperglycemic Conditions

Objectives: The process of autophagy is important for normal cellular homeostasis as it degrades proteins and damaged organelles. However, dysregulated autophagy is linked to a number of conditions, with preliminary data indicating a potential link between hyperglycemia and neuropathic pain associated with diabetes. Our objective was to identify the existence of this link, and determine potential treatments that can mitigate phenotypic outcomes.
Methods: Dorsal root ganglions from mice were cultured in low and high glucose conditions: 2 controls, 2 serum starved (SFM), and 2 SFM+rapamycin treated. Western blots were performed on whole cell lysates and results were quantitatively determined via densitometric analysis. Autophagy was quantified by observing LC3-I/-II conversion and Ulk-1 phosphorylation. Normalization of these measurements were identified as autophagic flux.
Results: Experimental results indicate reduced autophagic flux in hyperglycemic conditions. However, rapamycin treatment reversed this hyperglycemia effect, as evidenced by Western blot results. Taken together, rapamycin partially reversed the effects of hyperglycemia on cultured DRG neurons and may serve as as potential treatment for diabetic neuropathic pain.
Conclusions: Rapamycin is a life-extending drug with many positive effects such that is well-tolerated by patients. Rapamycin could serve as a potential treatment for diabetic neuropathic pain in future models.