Unlocking the multifaceted roles of GLP-1: Physiological functions and therapeutic potential
Open accessAbstract
Glucagon (GCG) like peptide 1 (GLP-1) has emerged as a powerful player in regulating metabolism and a promising therapeutic target for various chronic diseases. This review delves into the physiological roles of GLP-1, exploring its impact on glucose homeostasis, insulin secretion, and satiety. We examine the compelling evidence supporting GLP-1 receptor agonists (GLP-1RAs) in managing type 2 diabetes (T2D), obesity, and other diseases. The intricate molecular mechanisms underlying GLP-1RAs are explored, including their interactions with pathways like extracellular signal-regulated kinase 1/2 (ERK1/2), activated protein kinase (AMPK), cyclic adenine monophosphate (cAMP), mitogen-activated protein kinase (MAPK), and protein kinase C (PKC). Expanding our understanding, the review investigates the potential role of GLP-1 in cancers. Also, microribonucleic acid (RNA) (miRNAs), critical regulators of gene expression, are introduced as potential modulators of GLP-1 signaling. We delve into the link between miRNAs and T2D obesity and explore specific miRNA examples influencing GLP-1R function. Finally, the review explores the rationale for seeking alternatives to GLP-1RAs and highlights natural products with promising GLP-1 modulatory effects.
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GLP-1 slows gastric emptying, leading to prolonged satiety and reduced food intake.
“Additionally, GLP-1 slows gastric emptying, leading to prolonged satiety and reduced food intake [24].”
From A Narrative Review on GLP-1 Receptor Agonists for Obesity in Older Women: Maximizing Weight Loss While Preserving Lean Mass (2026) · cites this paper as [24]
GLP-1 suppresses glucagon secretion from pancreatic alpha cells, preventing excessive glucose production from the liver.
“Conversely, GLP-1 suppresses glucagon secretion from pancreatic alpha cells, preventing excessive glucose production from the liver.”
From A Narrative Review on GLP-1 Receptor Agonists for Obesity in Older Women: Maximizing Weight Loss While Preserving Lean Mass (2026) · cites this paper as [24]
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He, W., Wang, H., Zhao, C., Tian, X., Li, L., & Wang, H. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.29204 · Cited by 44 · see citing works
Zhu, Q., Luo, Y., Wen, Y., Wang, D., Li, J., & Fan, Z. (2023) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2023.01.049 · Cited by 44 · see citing works
Therapies for inter-relating diabetes and obesity – GLP-1 and obesity
Iepsen, E. W., Torekov, S. S., & Holst, J. J. (2014) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2014.965678 · Cited by 43 · see citing works
miR-7 Regulates GLP-1-Mediated Insulin Release by Targeting β-Arrestin 1
Matarese, A., Gambardella, J., Lombardi, A., Wang, X., & Santulli, G. (2020) · Cells · doi:10.3390/cells9071621 · Cited by 43 · see citing works
Zhu, E., Yang, Y., Zhang, J., Li, Y., Li, C., Chen, L., & Sun, B. (2016) · Oncotarget · doi:10.18632/oncotarget.13189 · Cited by 42 · see citing works
Cowart, K. (2020) · Annals of Pharmacotherapy · doi:10.1177/1060028019889064 · Cited by 42 · see citing works
Eelderink, C., Noort, M. W. J., Sözer, N., Koehorst, M., Holst, J. J., Deacon, C. F., Rehfeld, J. F., Poutanen, K. S., Vonk, R. J., Oudhuis, L. A. A. C. M., et al. (2016) · European Journal of Nutrition · doi:10.1007/s00394-016-1156-6 · Cited by 41 · see citing works
Jamali, N., Jalali, M., Saffari‐Chaleshtori, J., Samare-Najaf, M., & Samareh, A. N. (2020) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2020.01.009 · Cited by 41 · see citing works
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Treatment potential of the GLP-1 receptor agonists in type 2 diabetes mellitus: a review
Østergaard, L., Frandsen, C. S., & Madsbad, S. (2016) · Expert Review of Clinical Pharmacology · doi:10.1586/17512433.2016.1121808 · Cited by 38 · see citing works
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Flagged first, then by citations
13 of the 308 references couldn’t be matched to a known paper.
Research works printed but not linked: 3
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Cited by
Sorted by citations
Ngabea, M. A., & Dimeji, I. Y. (2025) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2025.152822 · Cited by 35 · see citing works
An Overview of Targeting Some Cancer Hallmarks with Plant Polyphenols: A Step Toward Precision
Hamdy, N. Μ., Amin, A., Abd-Ellatef, G. E. F., Abdalla, Y., Abdalla, A., Saqr, D. A., Lu, Y., Wu, W., El‐Din, M. I. G., & El-Shazly, M. (2026) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-3-032-08530-6_8 · Cited by 19 · see citing works
Semaglutide Enhances Cellular Regeneration in Skin and Retinal Cells In Vitro
Anastasiou, I. A., Tentolouris, A., Sarantis, P., Katsaouni, A., Rebelos, E., Mourouzis, I. S., Pantos, C. I., & Tentolouris, N. (2025) · Pharmaceutics · doi:10.3390/pharmaceutics17091115 · Cited by 17 · see citing works
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GLP-1 Receptor Agonists in Heart Failure
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“…actions of GLP-1, therefore, contribute to its dual benefits in weight management and glycemic control, making GLP-1 RAs effective agents for treating obesity and type 2 diabetes, particularly in older adults who are more prone to these conditions due to age-related physiological changes [24].”
Homoródi, N., Varga, É., Szabó, Z., Sztanek, F., & Harangi, M. (2025) · Biomedicines · doi:10.3390/biomedicines13112595 · Cited by 9 · see citing works
Food regulation of incretin axis: Molecular mechanisms and clinical outlook in diabetes
Huang, Q., Deng, H., Sun, M.-C., & Zhao, C. (2025) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2025.105326 · Cited by 8 · see citing works
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Agu, P. C., Yudas, A. F., & Lu, J. (2025) · Antioxidants · doi:10.3390/antiox14111364 · Cited by 5 · see citing works
The Role of Gene Therapy and RNA-Based Therapeutic Strategies in Diabetes
Khan, M., Al-Dhaleai, R. E., Alayadhi, S. M., Alhalwachi, Z., & Butler, A. E. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262110264 · Cited by 4 · see citing works
The Role of miR-802 in Diabetic Kidney Disease: Diagnostic and Therapeutic Insights
Tejera‐Muñoz, A., Marchant, V. A., Tejedor-Santamaria, L., Opazo-Ríos, L., Lavoz, C., Gimeno, M. J., Aceña, J. L., Ruiz‐Ortega, M., & Rodrigues-Díez, R. R. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26125474 · Cited by 4 · see citing works
Zhan, W., Wu, L., Li, S., Yin, G., Zhou, J., & Wu, Z. (2025) · Journal of Orthopaedic Surgery and Research · doi:10.1186/s13018-025-05945-3 · Cited by 3 · see citing works
Perl, A., & Banki, K. (2026) · Nature Reviews Rheumatology · doi:10.1038/s41584-026-01421-2 · Cited by 3 · see citing works
Bahtiar, A., Musyantika, L., Wahyuni, T., Utami, R. A., & Siriamornpun, S. (2026) · Foods · doi:10.3390/foods15071167 · Cited by 2 · see citing works
Liao, K., Tsai, Y., Κostikas, Κ., Criner, G. J., Wu, J.-Y., & Lai, C. (2026) · QJM · doi:10.1093/qjmed/hcag217 · Cited by 2 · see citing works
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Effects of chronic ethanol consumption on brain GLP-1R gene expression in mice and humans
Torregrosa, A. B., García‐Gutiérrez, M. S., Ortuño‐Miquel, S., & Manzanares, J. (2026) · Translational Psychiatry · doi:10.1038/s41398-026-03838-5 · Cited by 1 · see citing works
Protective Impact of GLP-1 Therapy on Post-ERCP Outcomes
Kazi, M. A. I., Khan, J., Mufarrih, S. M., Widmer, J., Al-Sabban, A. M., Irani, S. S., Baron, T. H., & Canakis, A. (2026) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0000000000002374 · Cited by 1 · see citing works
Glucagon-like peptide 1 receptor agonists: anti-inflammatory effects in cardiovascular diseases
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Sirtuin proteins: structure, functions, and evolutionary insights
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Ulusu, N. N. (2026) · Antioxidants · doi:10.3390/antiox15091143 · Cited by 1 · see citing works
GLP-1 as a Regulator of Oxidative Signalling in Metabolic Health and Disease
Kurhaluk, N., Kołodziejska, R., & Ткаченко, Г. М. (2026) · Antioxidants · doi:10.3390/antiox15101283
- Authors
- AL-Noshokaty, T. M., Abdelhamid, R., Abdelmaksoud, N. M., Khaled, A., Hossam, M., Ahmed, R., Saber, T., Khaled, S., Elshaer, S. S., & Abulsoud, A. I.
- Affiliations
- Heliopolis University (EG)
- Al-Azhar University (EG)
- Corresponding author
- Abdelhamid, Rehab
- Venue
- Toxicology Reports
- Publisher
- Elsevier BV
- Published
- 2025-06
- Volume
- 14
- Pages
- 101895
- ISSN
- 2214-7500 (ISSN-L)
- PMC
- PMC11795145
- OpenAlex
- W4406560873
- Cited by
- 30
- References
- 308
- Citations by year
- 2026: 16 · 2025: 14
- FWCI
- 4.08
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Toxicology Reports (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- glucagon-like peptide-1, GLP-1 receptor agonists, glucose homeostasis, insulin secretion, satiety, type 2 diabetes, obesity, cancer, microRNA, ERK signaling, AMPK, cAMP signaling, MAPK signaling, protein kinase C, natural products, GLP-1 signaling
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