Effect of Dipeptidyl Peptidase-IV (DPP-IV) Inhibitor (Vildagliptin) on Peripheral Nerves in Streptozotocin-induced Diabetic Rats
Received 26 June 2009; accepted 7 September 2009.
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 0.3mg/kg/day or 10mg/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 10mg/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 0.3mg/kg DPP-IV inhibitor (9.88±0.38), and DM with 10mg/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 0.3mg/kg DPP-IV inhibitor (13.3%), and DM with 10mg/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.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, South Korea
Address reprint requests to: Tae Sun Park, M.D., Ph.D., Division of Endocrinology and Metabolism, Department of Internal Medicine, Chonbuk National University Medical School, 634-18, Keum-Am Dong, Jeonju, 561-712, South Korea; Phone: 82-63-250-1794; FAX: 82-63-254-1609
ABSTRACT