Reviews in Endocrine and Metabolic Disorders

, Volume 15, Issue 3, pp 219–231

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

  • Jan Hansen
  • Birgitte Brock
  • Hans Erik Bøtker
  • Albert Gjedde
  • Jørgen Rungby
  • Michael Gejl
Article

DOI: 10.1007/s11154-014-9286-8

Cite this article as:
Hansen, J., Brock, B., Bøtker, H.E. et al. Rev Endocr Metab Disord (2014) 15: 219. doi:10.1007/s11154-014-9286-8

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.

Keywords

GLP-1  Myocardial glucose metabolism 

Abbreviations

T2D

Type 2 diabetes mellitus

PET

Positron emission tomography

MGU

Myocardial glucose uptake

GLP-1

Glucagon-like peptide-1

CVD

Cardiovascular disease

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Jan Hansen
    • 1
  • Birgitte Brock
    • 1
    • 2
  • Hans Erik Bøtker
    • 7
  • Albert Gjedde
    • 4
    • 5
    • 6
  • Jørgen Rungby
    • 8
  • Michael Gejl
    • 1
    • 3
  1. 1.Department of Biomedicine-PharmacologyAarhus UniversityAarhus CDenmark
  2. 2.Department of Clinical BiochemistryAarhus University HospitalAarhus CDenmark
  3. 3.Department of Endocrinology and Internal MedicineAarhus University HospitalAarhusDenmark
  4. 4.Department of Neuroscience and PharmacologyUniversity of Copenhagen, Panum InstituteCopenhagenDenmark
  5. 5.Department of Radiology and Radiological ScienceJohns Hopkins UniversityBaltimoreUSA
  6. 6.Department of Neurology and NeurosurgeryMcGill UniversityMontréalCanada
  7. 7.Department of CardiologyAarhus University HospitalAarhusDenmark
  8. 8.Diabetes Research Division, Department of MedicineCopenhagen University HospitalGentofteDenmark

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