FIGURE 4.

ARI or vitamin D treatment rescues diabetic neuropathy in type I or type II DM model mice in vivo. STZ (A–E) or db/db (F–J) mice were treated with ARI, ED71 (ED), or vehicle for 4 weeks. Subsequently, sorbitol levels in sciatic nerves were analyzed (A and F), and motor or sensory capacity was tested by ROTA-ROD or a DigiGate system (B and G) or von Frey (C and H) tests, respectively. Nerve conduction velocity was also analyzed (D and I). Data represent means ± S.D. of sorbitol (mg/liter, A and F), time on the ROTA-ROD (seconds, B), stride length (relative to WT, G), tactile threshold (seconds, C and H), or NCV (m/s, D and I). E and J, MAG, MBP, P0, and P75 expression relative to Actb was analyzed in sciatic nerves of STZ (E) or db/db (J) mice. Data represent means ± S.D. of (MAG, MBP, P0, or p75)/Actb levels (*, p < 0.05; **, p < 0.01; ***, p < 0.001, NS, not significant; n = 5 nerves each). Electron microscopy analysis of sciatic nerves from control (NC) or db/db mice (DM) treated with or without ARI or ED71 (K). The extent of myelination was measured by G ratio determination (L) and calculation of density of myelinated (M) or de-myelinated (N) fibers. Representative data of at least two independent experiments are shown.