Cardiovascular Drugs and Therapy

, Volume 25, Issue 1, pp 13–20 | Cite as

Pre-treatment with a DPP-4 Inhibitor is Infarct Sparing in Hearts from Obese, Pre-diabetic Rats

  • Barbara Huisamen
  • Amanda Genis
  • Erna Marais
  • Amanda Lochner
Article

Abstract

Cardiovascular risk is closely associated with insulin resistance and type 2 diabetes. Therapy based on the actions of GLP-1 is currently seen as a novel approach to treat this disease. The aims of this study was therefore to use an animal model to determine whether (i) pre-treatment of obese, insulin resistant but pre-diabetic rats with a DPP4 inhibitor, PFK275-055, could protect the heart from ischaemia/reperfusion injury and (ii) the possible mechanisms involved in such protection. Obese, pre-diabetic rats (DIO) were treated for 4 weeks with 10 mg/kg/day of the DPP4 inhibitor PFK275-055. Ex vivo perfusion was used to subject hearts to ischaemia/reperfusion to determine infarct size, functional recovery and post-ischaemic activation of proteins associated with cardiac protection. Adult ventricular cardiomyocytes were isolated to determine insulin sensitivity. Other assessments included body weight, intra-peritoneal fat weight, insulin and GLP-1 levels as well as histological evaluation of the pancreata. Results showed that DIO animals had higher body mass and intra-peritoneal fat mass than chow-fed animals. They presented with elevated plasma insulin levels and lower GLP-1 levels. Treatment with the DPP4 inhibitor resulted in smaller infarct size development in hearts from DIO rats after ischaemia/reperfusion accompanied by activation of cardioprotective kinases. GLP-1 levels were elevated and plasma insulin levels lower after treatment. In addition, the beta-cell to alpha-cell ratio of the pancreas was improved. We conclude that treatment with PFK275-055 for 4 weeks protected the heart against ischaemia/reperfusion injury, elevated GLP-1 levels and improved metabolic control in obese, pre-diabetic rats.

Key words

DPP4 inhibitor Heart Insulin resistance Obesity 

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Barbara Huisamen
    • 1
    • 2
  • Amanda Genis
    • 2
  • Erna Marais
    • 2
  • Amanda Lochner
    • 1
    • 2
  1. 1.MRC Cape Heart CentreCape TownRepublic of South Africa
  2. 2.Department of Biomedical Sciences, Division Physiology, Faculty of Health SciencesUniversity of StellenboschTygerbergRepublic of South Africa

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