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

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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.

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Authors and Affiliations

  1. MRC Cape Heart Centre, Cape Town, Republic of South Africa

    Barbara Huisamen & Amanda Lochner

  2. Department of Biomedical Sciences, Division Physiology, Faculty of Health Sciences, University of Stellenbosch, P.O. Box 19063, Tygerberg, 7505, Republic of South Africa

    Barbara Huisamen, Amanda Genis, Erna Marais & Amanda Lochner

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  1. Barbara Huisamen
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  2. Amanda Genis
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  3. Erna Marais
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  4. Amanda Lochner
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Correspondence to Barbara Huisamen.

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Huisamen, B., Genis, A., Marais, E. et al. Pre-treatment with a DPP-4 Inhibitor is Infarct Sparing in Hearts from Obese, Pre-diabetic Rats. Cardiovasc Drugs Ther 25, 13–20 (2011). https://doi.org/10.1007/s10557-010-6271-7

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  • DOI: https://doi.org/10.1007/s10557-010-6271-7

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