Effect of dipeptidyl peptidase-IV (DPP-IV) inhibitor (Vildagliptin) on peripheral nerves in streptozotocin-induced diabetic rats

Arch Med Res. 2009 Oct;40(7):536-44. doi: 10.1016/j.arcmed.2009.09.005.

Abstract

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.

MeSH terms

  • Adamantane / analogs & derivatives*
  • Adamantane / pharmacology
  • Animals
  • Blood Glucose / metabolism
  • Body Weight
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / pathology*
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology*
  • Eating
  • Electric Stimulation
  • Epidermis / innervation
  • Glucagon-Like Peptide 1 / blood
  • Humans
  • Insulin / blood
  • Male
  • Nerve Degeneration / etiology
  • Nerve Degeneration / pathology
  • Nitriles / pharmacology*
  • Peripheral Nerves / cytology
  • Peripheral Nerves / drug effects*
  • Peripheral Nerves / metabolism
  • Peripheral Nerves / pathology
  • Pyrrolidines / pharmacology*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Ubiquitin Thiolesterase / genetics
  • Ubiquitin Thiolesterase / metabolism
  • Vildagliptin

Substances

  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Insulin
  • Nitriles
  • Pyrrolidines
  • Glucagon-Like Peptide 1
  • UCHL1 protein, rat
  • Ubiquitin Thiolesterase
  • Vildagliptin
  • Adamantane