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Impact of glucagon-like peptide-1 on myocardial glucose metabolism revisited

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Abstract

The gut hormone glucagon-like peptide-1 (GLP-1) is an insulinotropic incretin with significant cardiovascular impact. Two classes of medication, GLP-1 analogues and DPP-4 inhibitors, have been developed that circumvent the rapid degradation of GLP-1 by the enzyme dipeptidyl peptidase-4 (DPP-4), both enhance the incretin effect and were developed for the treatment of type 2 diabetes. Several mechanisms suggesting that DPP-4 inhibitors, GLP-1, and analogues could have a protective effect on the cardiovascular risk profile have been forwarded; e.g., reductions of blood glucose, body weight, blood pressure, improvement in left ventricular ejection fraction, myocardial perfusion, atherosclerosis development, and endothelial function. Despite this, the reasons for a decreased risk of developing cardiovascular disease and reduced post-ischaemia damage are still poorly understood. The potentially beneficial effect of GLP-1 stimulation may rely on, among others, improved myocardial glucose metabolism. This review focuses on the dogma that GLP-1 receptor stimulation may provide beneficial cardiovascular effects, possibly due to enhanced myocardial energetic efficiency, by increasing myocardial glucose uptake. The published literature was systematically reviewed and the applied models evaluated since the outcomes of varying studies differ substantially. Reports on the effect of GLP-1R stimulation on myocardial metabolism are conflicting and should be evaluated carefully. There is limited and conflicting information on the impact of these agents in real life patients and while clinical outcome studies investigating the cardiovascular effects of GLP-1 based therapies have been initiated, the first two studies, both on DPP-4 inhibitors, designed specifically to evaluate cardiac safety reported largely neutral outcomes.

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Abbreviations

T2D:

Type 2 diabetes mellitus

PET:

Positron emission tomography

MGU:

Myocardial glucose uptake

GLP-1:

Glucagon-like peptide-1

CVD:

Cardiovascular disease

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Authors and Affiliations

  1. Department of Biomedicine-Pharmacology, Aarhus University, University Park 1240, DK-8000, Aarhus C, Denmark

    Jan Hansen, Birgitte Brock & Michael Gejl

  2. Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus C, Denmark

    Birgitte Brock

  3. Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark

    Michael Gejl

  4. Department of Neuroscience and Pharmacology, University of Copenhagen, Panum Institute, Blegdamsvej 3B, 2200, Copenhagen, Denmark

    Albert Gjedde

  5. Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, 21287, USA

    Albert Gjedde

  6. Department of Neurology and Neurosurgery, McGill University, Montréal, Québec, H3A 2B4, Canada

    Albert Gjedde

  7. Department of Cardiology, Aarhus University Hospital, Skejby, Aarhus, Denmark

    Hans Erik Bøtker

  8. Diabetes Research Division, Department of Medicine, Copenhagen University Hospital, Gentofte, Hellerup, Denmark

    Jørgen Rungby

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Hansen, J., Brock, B., Bøtker, H.E. et al. Impact of glucagon-like peptide-1 on myocardial glucose metabolism revisited. Rev Endocr Metab Disord 15, 219–231 (2014). https://doi.org/10.1007/s11154-014-9286-8

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