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Diabetic Neuropathy

Understanding the pathophysiology of diabetic neuropathy

Preclinical Efficacy Model of Diabetic Neuropathy

The most commonly used model is the streptozotocin (STZ) -treated rat. STZ is a cytotoxic agent derived from the gram-positive Streptomyces acromogenes bacterium that selectively kills pancreatic β-cells. Administering a single, low-dose STZ injection to healthy, adult rats results in their rapid development of a condition much like T1D in humans, where lack of functional β-cells in pancreatic islets impairs normal glycemic control. Treated animals become hyperglycemic within 72 hours of injection and develop significant neuropathic pain symptoms after approximately 4 weeks. This hyperglycemic nerve ending damage occurs through either the inflammatory process or interference with the blood supply (ischemia of the micro vessels). 


In addition to the mechanisms related to the hyperglycemic state, studies also suggest a mechanism of neuronal damage that occurs folowing STZ that is unrelated to the hyperglycemic state. The studies suggest that there is direct damage to the nerves via ROS-mediated elevation of TRPVI in the neurons. Some in vitro studies also suggest that DRG is exposed to the STZ. This suggests that this model involves direct changes in the nerves that are not related to the inflammatory process. 


Covered in this Whitepaper
  • Background of Diabetic Neuropathy
  • Commonly used preclinical models
  • STZ Diabetic Neuropathy
  • Representative data