Beneficial effects of vildagliptin on retinal injury in obese type 2 diabetic rats

Ophthalmic Res. 2013;50(4):221-6. doi: 10.1159/000354116. Epub 2013 Sep 25.

Abstract

Background/aims: Vildagliptin is an oral inhibitor of dipeptidyl peptidase-4, an enzyme mainly responsible for inactivating incretins, and one of the widely used drugs for the treatment of type 2 diabetes. However, effects of vildagliptin on retinal injury in diabetes remain unclear. We examined here whether oral administration of vildagliptin inhibited gene expression of inflammatory and thrombogenic parameters in Otsuka Long-Evans Tokushima Fatty rats (OLETF rats), an animal model of obese type 2 diabetes.

Methods: OLETF rats at 22 weeks of age were given vehicle or 3 mg/kg of vildagliptin for another 10 weeks. Gene expression was analyzed in quantitative real-time reverse transcription-polymerase chain reaction.

Results: Vildagliptin significantly inhibited the increase in body weight and decreased average fasting blood glucose in the OLETF rats. Compared with 22-week-old OLETF rats, gene expression levels of vascular endothelial growth factor, intercellular adhesion molecule-1, plasminogen activator inhibitor-1 and pigment epithelium-derived factor were significantly increased in the retinas of OLETF rats at 32 weeks of age, all of which were inhibited by treatment with vildagliptin.

Conclusions: The present study demonstrated for the first time that vildagliptin inhibited inflammatory and thrombogenic reactions in the retinas of obese type 2 diabetic rats. Vildagliptin may play a protective role against diabetic retinopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adamantane / analogs & derivatives*
  • Adamantane / therapeutic use
  • Administration, Oral
  • Analysis of Variance
  • Animals
  • Biomarkers / metabolism
  • Blood Glucose / drug effects
  • Blood Pressure / drug effects
  • Body Weight / drug effects
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetic Retinopathy / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Gene Expression Profiling
  • Male
  • Nitriles / therapeutic use*
  • Obesity / complications*
  • Pyrrolidines / therapeutic use*
  • Rats
  • Real-Time Polymerase Chain Reaction
  • Retina / drug effects
  • Retina / metabolism
  • Vildagliptin

Substances

  • Biomarkers
  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Nitriles
  • Pyrrolidines
  • Vildagliptin
  • Adamantane