Anti‐inflammatory effects of exendin‐4, a glucagon‐like peptide‐1 analog, on human peripheral lymphocytes in patients with type 2 diabetes
Open accessAbstract
Aims/Introduction: Type 2 diabetes is characterized by dysregulation of immunity, oxidative stress and reduced incretin effects. Experimental studies suggest that glucagon‐like peptide (GLP‐1) might have immunomodulating effects. We hypothesize that GLP‐1 receptor agonist, exendin‐4, might reduce inflammatory response in type 2 diabetes. Materials and Methods: Using peripheral blood mononuclear cells (PBMC) sampled from 10 type 2 diabetes and 10 sex‐ and age‐matched control subjects and supernatants from PBMC culture, the expression of phospho‐mitogen activated protein kinase (MAPK) signaling pathways in CD 4+ T helper lymphocytes and monocytes was analyzed using flow cytometry. Cytokines/chemokines and superoxide anion before and after treatment with exendin‐4 were measured by cytometric bead array and chemiluminesence assay, respectively. Results: Compared with control subjects, PBMC from type 2 diabetes patients showed activated MAPK (P 38, c‐Jun NH 2‐terminal protein kinase and extracellular signal‐regulated kinase) signaling pathway, elevated superoxide anion, increased pro‐inflammatory cytokines (tumor necrosis factor‐α, interleukin‐1β, interleukin‐6) and chemokines (CCL 5/regulated on activation normal T‐cell expressed and secreted and CXCL 10/interferon‐γ‐induced protein 10). These changes were attenuated by exendin‐4, possibly through the suppression of p38 MAPK. Conclusions: These results suggest that exendin‐4 might downregulate pro‐inflammatory responses and reduce oxidative stress by suppressing MAPK signaling pathways in type 2 diabetes.
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Therapy with exenatide may decrease oxidative stress and upregulate anti-inflammatory responses in the peripheral lymphocytes of type 1 and T2D patients.
“Another research found that therapy with exenatide may decrease oxidative stress and upregulate anti-inflammatory responses in the peripheral lymphocytes of type 1 and T2D patients. 71”
From Anti-inflammatory role of glucagon-like peptide 1 receptor agonists and its clinical implications (2024) · cites this paper as [71]
The Results and Discussion report that ex vivo exendin-4 treatment reduced superoxide production and pro-inflammatory cytokines in peripheral blood mononuclear cells from patients with type 2 diabetes (page numbers unavailable). The study did not test therapy in patients with type 1 diabetes, and it reports suppression of pro-inflammatory activity rather than upregulation of anti-inflammatory responses. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn peripheral blood mononuclear cells isolated from people with type 2 diabetes, exendin-4 reduced the expression and production of proinflammatory cytokines and chemokines, in association with a reduction in oxidative stress.
“In peripheral blood mononuclear cells isolated from people with T2D, exendin-4 reduced the expression and production of proinflammatory cytokines and chemokines, in association with a reduction in oxidative stress (44).”
From GLP-1 agonists in the treatment of chronic kidney disease in type 2 diabetes and obesity (2025) · cites this paper as [44]
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- Authors
- He, L., Wong, C. K., Cheung, K. K., Yau, H. C., Fu, A., Zhao, H., Leung, K. M., Kong, A. P., Wong, G. W., Chan, P. K., Xu, G., & Chan, J. C.
- Affiliations
- Chinese University of Hong Kong (HK)
- Department of Chemical Pathology The Chinese University of Hong Kong Shatin Hong Kong SAR China
- Corresponding author
- Chan, Juliana CN
- ORCID
- Venue
- Journal of Diabetes Investigation
- Publisher
- Wiley
- Published
- 2013-04-18
- Volume
- 4
- Issue
- 4
- Pages
- 382-392
- ISSN
- 2040-1116 (ISSN-L)
- 2040-1124
- PMC
- PMC4020234
- OpenAlex
- W2170781124
- Cited by
- 70
- References
- 48
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 3 · 2023: 2 · 2022: 8 · 2021: 7 · 2020: 4 · 2019: 6 · 2018: 3 · 2017: 7 · 2016: 7 · 2015: 9 · 2014: 1 · 2013: 2
- FWCI
- 4.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Diabetes Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Hong Kong Government Research Grants Council (CUHK4462/06M)
- Hong Kong Jockey Club Charities Trust (JCICM-P2-05 CUHK)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
- Keywords
- exendin-4, glucagon-like peptide-1, type 2 diabetes, anti-inflammatory activity, peripheral blood mononuclear cells, CD4+ T helper cells, monocytes, MAPK signaling, p38 MAPK, oxidative stress, superoxide, inflammatory cytokines, chemokines, immunomodulation
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