4.6 Article

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

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ARCHIVES OF MEDICAL RESEARCH
卷 40, 期 7, 页码 536-544

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ELSEVIER SCIENCE INC
DOI: 10.1016/j.arcmed.2009.09.005

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DPP-IV inhibitor; Diabetes; GLP-1 pathway; Peripheral nerve

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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. (C) 2009 IMSS. Published by Elsevier Inc.

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