A long-acting glucagon-like peptide-1 analogue attenuates induction of plasminogen activator inhibitor type-1 and vascular adhesion molecules
Open accessAbstract
Glucagon-like peptide-1 (GLP-1) administration attenuates endothelial cell dysfunction in diabetic patients and inhibits tumour necrosis factor α (TNF)-mediated plasminogen activator inhibitor type-1 (PAI-1) induction in human vascular endothelial cells. The short half-life of GLP-1 mediated via degradation by the enzyme dipeptidyl peptidase 4 mandates the clinical use of long-acting GLP-1 analogues. The effects of a long-acting GLP-1 analogue on PAI-1 and vascular adhesion molecule expression in vascular endothelial cells are unknown. In this report, we demonstrate for the first time that the treatment with liraglutide, a long-acting GLP-1 analogue, inhibited TNF or hyperglycaemia-mediated induction of PAI-1, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 mRNA and protein expression in a human vascular endothelial cell line. In addition, treatment attenuated TNF- or hyperglycaemia-mediated induction of the orphan nuclear receptor Nur77 mRNA expression. Taken together, these observations indicate that liraglutide inhibits TNF- or glucose-mediated induction of PAI-1 and vascular adhesion molecule expression, and this effect may involve the modulation of NUR77. These effects suggest that liraglutide may potentially improve the endothelial cell dysfunction associated with premature atherosclerosis identified in type 2 diabetic patients.
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GLP-1-based therapies show anti-inflammatory effects on the liver, vascular system including aorta and vein endothelial cells, brain, kidney, lung, testis, and skin by reducing the production of inflammatory cytokines and infiltration of immune cells in the tissues.
“emerging data suggest that GLP-1-based therapies also showed anti-inflammatory effects on the liver, vascular system including aorta and vein endothelial cells, brain, kidney, lung, testis, and skin by reducing the production of inflammatory cytokines and infiltration of immune cells in the tissues [17, 21–25].”
From Anti-Inflammatory Effects of GLP-1-Based Therapies beyond Glucose Control (2016) · cites this paper as [23]
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- Authors
- Liu, H., Dear, A. E., Knudsen, L. B., & Simpson, R. W.
- Affiliations
- Monash University (AU)
- Novo Nordisk (Denmark) (DK)
- Eastern Health (AU)
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 2009-01-09
- Volume
- 201
- Issue
- 1
- Pages
- 59-66
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- OpenAlex
- W2128077095
- Cited by
- 187
- References
- 2
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 7 · 2023: 10 · 2022: 5 · 2021: 7 · 2020: 8 · 2019: 14 · 2018: 10 · 2017: 7 · 2016: 12 · 2015: 9 · 2014: 13 · 2013: 13 · 2012: 23
- FWCI
- 12.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Monash University
- Novo Nordisk
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- liraglutide, glucagon-like peptide-1 analogues, plasminogen activator inhibitor-1, vascular adhesion molecules, ICAM-1, VCAM-1, Nur77, TNF-α, hyperglycemia, endothelial dysfunction, type 2 diabetes, premature atherosclerosis, dipeptidyl peptidase IV
- MeSH terms
- Liraglutide, Cells, Cultured, Delayed-Action Preparations, DNA-Binding Proteins, Humans, Hyperglycemia, Receptors, Steroid, Tumor Necrosis Factor-alpha, Down-Regulation, Cell Adhesion Molecules, Plasminogen Activator Inhibitor 1, Intercellular Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1, Endothelial Cells, Glucagon-Like Peptide 1, Nuclear Receptor Subfamily 4, Group A, Member 1
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