Cited by 174Diabetes Treatment and ManagementNitric Oxide and Endothelin EffectsDiabetes, Cardiovascular Risks, and Lipoproteins

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Exenatide Protects Against Glucose- and Lipid-Induced Endothelial Dysfunction: Evidence for Direct Vasodilation Effect of GLP-1 Receptor Agonists in Humans

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Koska, Juraj, Sands, Michelle, Burciu, Camelia, D’Souza, Karen M., Raravikar, Kalyani, Liu, James, Truran, Seth, Franco, Daniel A., Schwartz, Eric A., Schwenke, Dawn C., D’Alessio, David, Migrino, Raymond Q., Reaven, Peter D.·2015·Diabetes

DOI 10.2337/db14-0976PMC PMC4477348

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Abstract

GLP-1 receptor (GLP-1R) agonists may improve endothelial function (EF) via metabolic improvement and direct vascular action. The current study determined the effect of GLP-1R agonist exenatide on postprandial EF in type 2 diabetes and the mechanisms underlying GLP-1R agonist–mediated vasodilation. Two crossover studies were conducted: 36 participants with type 2 diabetes received subcutaneous exenatide or placebo for 11 days and EF, and glucose and lipid responses to breakfast and lunch were determined; and 32 participants with impaired glucose tolerance (IGT) or diet-controlled type 2 diabetes had EF measured before and after intravenous exenatide, with or without the GLP-1R antagonist exendin-9. Mechanisms of GLP-1R agonist action were studied ex vivo on human subcutaneous adipose tissue arterioles and endothelial cells. Subcutaneous exenatide increased postprandial EF independent of reductions in plasma glucose and triglycerides. Intravenous exenatide increased fasting EF, and exendin-9 abolished this effect. Exenatide elicited eNOS activation and NO production in endothelial cells, and induced dose-dependent vasorelaxation and reduced high-glucose or lipid-induced endothelial dysfunction in arterioles ex vivo. These effects were reduced with AMPK inhibition. In conclusion, exenatide augmented postprandial EF in subjects with diabetes and prevented high-glucose and lipid-induced endothelial dysfunction in human arterioles. These effects were largely direct, via GLP-1R and AMPK activation.

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Self-citation

Authors: Koska, J., Sands, M., Burciu, C., D’Souza, K. M., Raravikar, K., Liu, J., Truran, S., Franco, D. A., Schwartz, E. A., Schwenke, D. C., D’Alessio, D., Migrino, R. Q., & Reaven, P. D.
Affiliations: Department of Medicine, Phoenix VA Health Care System, Phoenix, AZ
Phoenix VA Health Care System (US)
Duke University (US)
ORCID: Burciu, Camelia
Truran, Seth
Franco, Daniel A.
Schwenke, Dawn C.
D’Alessio, David
Migrino, Raymond Q.
Reaven, Peter D.
Venue: Diabetes
Publisher: American Diabetes Association
Published: 2015-02-26
Volume: 64
Issue: 7
Pages: 2624-2635
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/db14-0976
PMC: PMC4477348
OpenAlex: W2130583827
Cited by: 174
References: 52
Citations by year: 2026: 17 · 2025: 27 · 2024: 20 · 2023: 11 · 2022: 20 · 2021: 14 · 2020: 6 · 2019: 13 · 2018: 14 · 2017: 16 · 2016: 12 · 2015: 4
FWCI: 13.30
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.diabetesjournals.org/site/license (vor, 309 d)
Locations: Diabetes (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Heart, Lung, and Blood Institute (R21HL-092344-01)
U.S. Department of Veterans Affairs (1I01CX000598, BLRD I01BX007080)
American Diabetes Association (1-10-CT-31)
Amyloidosis Foundation
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords: exenatide, GLP-1 receptor agonists, endothelial dysfunction, vasodilation, type 2 diabetes, impaired glucose tolerance, AMPK, endothelial nitric oxide synthase, nitric oxide, high glucose, hypertriglyceridemia, endothelial cells
MeSH terms: Glucagon-Like Peptide-1 Receptor, Exenatide, Blood Glucose, Cells, Cultured, Diabetes Mellitus, Type 2, Double-Blind Method, Female, Humans, Male, Peptides, Triglycerides, Vasodilation, Venoms, Receptors, Glucagon, Cross-Over Studies, Endothelial Cells, AMP-Activated Protein Kinases

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Exenatide Protects Against Glucose- and Lipid-Induced Endothelial Dysfunction: Evidence for Direct Vasodilation Effect of GLP-1 Receptor Agonists in Humans

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