Cited by 284Diabetes Treatment and ManagementAdipokines, Inflammation, and Metabolic DiseasesPeroxisome Proliferator-Activated Receptors

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Exenatide Exerts a Potent Antiinflammatory Effect

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Chaudhuri, Ajay, Ghanim, Husam, Vora, Mehul, Sia, Chang Ling, Korzeniewski, Kelly, Dhindsa, Sandeep, Makdissi, Antoine, Dandona, Paresh·2012·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jc.2011-1508PMC PMC3251936

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Abstract

OBJECTIVE: Our objective was to determine whether exenatide exerts an antiinflammatory effect. RESEARCH DESIGN AND METHODS: Twenty-four patients were prospectively randomized to be injected sc with either exenatide 10 μg twice daily [n = 12; mean age = 56 ± 3 yr; mean body mass index = 39.8 ± 2 kg/m(2); mean glycosylated hemoglobin (HbA1c) = 8.6 ± 0.4%] or placebo twice daily (n = 12; mean age = 54 ± 4 yr; mean body mass index = 39.1 ± 1.6 kg/m(2); mean HbA1c = 8.5 ± 0.3%) for 12 wk. Fasting blood samples were obtained at 0, 3, 6, and 12 wk. Blood samples were also collected for up to 6 h after a single dose of exenatide (5 μg) or placebo. RESULTS: Fasting blood glucose fell from 139 ± 17 to 110 ± 9 mg/dl, HbA1c from 8.6 ± 0.4 to 7.4 ± 0.5% (P < 0.05), and free fatty acids by 21 ± 5% from baseline (P < 0.05) with exenatide. There was no weight loss. There was a significant reduction in reactive oxygen species generation and nuclear factor-κB binding by 22 ± 9 and 26 ± 7%, respectively, and the mRNA expression of TNFα, IL-1β, JNK-1, TLR-2, TLR-4, and SOCS-3 in mononuclear cells by 31 ± 12, 22 ± 10, 20 ± 11, 22 ± 9, 16 ± 7, and 31 ± 10%, respectively (P < 0.05 for all) after 12 wk of exenatide. After a single injection of exenatide, there was a reduction by 20 ± 7% in free fatty acids, 19 ± 7% in reactive oxygen species generation, 39 ± 11% in nuclear factor-κB binding, 18 ± 9% in TNFα expression, 26 ± 7% in IL-1β expression, 18 ± 7% in JNK-1 expression, 24 ± 12% in TLR-4 expression, and 23 ± 11% in SOCS-3 expression (P < 0.05 for all). The plasma concentrations of monocyte chemoattractant protein-1, matrix metalloproteinase-9, serum amyloid A, and IL-6 were suppressed after 12 wk exenatide treatment by 15 ± 7, 20 ± 11, 16 ± 7, and 22 ± 12%, respectively (P < 0.05 for all). CONCLUSIONS: Exenatide exerts a rapid antiinflammatory effect at the cellular and molecular level. This may contribute to a potentially beneficial antiatherogenic effect. This effect was independent of weight loss.

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Authors: Chaudhuri, A., Ghanim, H., Vora, M., Sia, C. L., Korzeniewski, K., Dhindsa, S., Makdissi, A., & Dandona, P.
Affiliations: University at Buffalo, State University of New York (US)
Kaleida Health (US)
Corresponding author: Dandona, Paresh
ORCID: Ghanim, Husam
Dhindsa, Sandeep
Dandona, Paresh
Venue: The Journal of Clinical Endocrinology & Metabolism
Publisher: The Endocrine Society
Published: 2012-01
Volume: 97
Issue: 1
Pages: 198-207
ISSN: 0021-972X (ISSN-L)
1945-7197
DOI: 10.1210/jc.2011-1508
PMC: PMC3251936
OpenAlex: W2055611619
Cited by: 284
References: 38
Citations by year: 2026: 26 · 2025: 35 · 2024: 20 · 2023: 25 · 2022: 27 · 2021: 16 · 2020: 12 · 2019: 16 · 2018: 17 · 2017: 14 · 2016: 18 · 2015: 12 · 2014: 16 · 2013: 18 · 2012: 12
FWCI: 12.05
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: American Diabetes Association
National Institutes of Health (5r01dk069805-04)
University at Buffalo
National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK069805, R01DK075877)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Keywords: exenatide, anti-inflammatory activity, type 2 diabetes, NF-κB, reactive oxygen species, free fatty acids, TNF-α, IL-1β, TLR2, TLR4, JNK1, SOCS3, mononuclear cells, blood glucose, HbA1c, GLP-1 receptor agonists
MeSH terms: Exenatide, Anti-Inflammatory Agents, Blood Glucose, Diabetes Mellitus, Type 2, Drug Administration Schedule, Fatty Acids, Nonesterified, Humans, Hypoglycemic Agents, Insulin, Middle Aged, Obesity, Peptides, Placebos, Time Factors, Venoms, Single-Blind Method, Treatment Outcome, Reactive Oxygen Species

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