Effect of Dipeptidyl Peptidase-IV (DPP-IV) Inhibitor (Vildagliptin) on Peripheral Nerves in Streptozotocin-induced Diabetic Rats

Background and Aims: The aim of this study was to investigate the GLP-1 pathway effect on peripheral nerves using a DPP-IV inhibitor in streptozotocin (STZ)-induced diabetic rats. Methods: Adult male Sprague Dawley rats were divided into four groups and two groups (n = 6 in each) were given a DPP-IV inhibitor of 0.3 mg/kg/day or 10 mg/kg/day dissolved in water. Intraepidermal innervation was quantified as nerve fiber abundance per unit length of epidermis (IENF/mm) following an immunohistochemical procedure using the polyclonal antibody of anti-protein gene product 9.5 (PGP 9.5). Results: Daily administration of DPP-IV inhibitor to the experimental diabetes model at doses of 10 mg/kg for 32 weeks protected nerve fiber loss compared with untreated rats as follows (IENF/mm): normal (9.89 ± 0.34), diabetes mellitus (DM) (8.42 ± 0.28), DM with 0.3 mg/kg DPP-IV inhibitor (9.88 ± 0.38), and DM with 10 mg/kg DPP-IV inhibitor (10.36 ± 0.32) (p <0.05). There was a significant reduction (% change) in the decrease of intraepidermal nerve fiber density (IENFD) in the DPP-IV inhibitor-treated groups during the experimental period: normal (10.1%), DM (25.8%), DM with 0.3 mg/kg DPP-IV inhibitor (13.3%), and DM with 10 mg/kg DPP-IV inhibitor (7.9%) (p <0.05). Conclusions: Our study suggests that a DPP-IV inhibitor may prevent peripheral nerve degeneration in a diabetes-induced animal model and support the idea that GLP-1 may be useful in peripheral neuropathy.