HMGB1 and Hyperglycemia: The immunohistochemical studies of HMGB1 in the spinal cord dorsal horn of ob/ob mice exhibited hyperglycemia mediated HMGB1 release, predominantly from neuronal cells, and treatment with GLC inhibited the release of HMGB1 from the neuronal cells to the cytoplasm or to the extracellular space (Figure 3), which was also validated by Western blot analysis and the immunohistochemistry of the DRG of ZDF rats with painful diabetic neuropathy (PDN) (Figure 2 and Figure 4).