Peripheral neuropathy is a chronic complication of diabetes mellitus. To investigated the efficacy and safety of the extended\ntreatment of diabetic peripheral neuropathy with thymosin ?4 (T?4), male diabetic mice (db/db) at the age of 24 weeks were\ntreatedwith T?4 or saline for 16 consecutive weeks. Treatment of diabetic mice with T?4 significantly improved motor (MCV) and\nsensory (SCV) conduction velocity in the sciatic nerve and the thermal and mechanical latency. However, T?4 treatment did not\nsignificantly alter blood glucose levels. Treatment with T?4 significantly increased intraepidermal nerve fiber density. Furthermore,\nT?4 counteracted the diabetes-induced axon diameter and myelin thickness reductions and the ?-ratio increase in sciatic nerve.\nIn vitro, compared with dorsal root ganglia (DRG) neurons derived from nondiabetic mice, DRG neurons derived from diabetic\nmice exhibited significantly decreased neurite outgrowth, whereas T?4 promoted neurite growth in these diabetic DRG neurons.\nBlockage of the Ang1/Tie2 signaling pathway with a neutralized antibody against Tie2 abolished T?4-increased neurite outgrowth.\nOur data demonstrate that extended T?4 treatment ameliorates diabetic-induced axonal degeneration and demyelination, which\nlikely contribute to therapeutic effect of T?4 on diabetic neuropathy.The Ang1/Tie2 pathway may mediate T?4-induced axonal\nremodeling.
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