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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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![Fig. 1 Pleiotropic effects of GLP-1 [1]. [CNS: central nervous system; CVS: Cardiovascular system; GIT: Gastrointestinal tract; GLP-1R: Glucagon like peptide-1 receptor; VLDL: very low-density lipoprotein].](/paper-figures/6f2a32aec74643f08815438421405ffb/unlocking-the-multifaceted-roles-of-glp-1-physiological-functions-and-figure-1.jpg)
![Fig. 2 The complex interplay between GLP-1RAs and several cellular signaling pathways. [AMPK: activated protein kinase; cAMP: cyclic adenine monophosphate; ERK 1/2: extracellular signal-regulated kinase 1/2; GLP-1R: Glucagon like peptide-1 receptor; MAPK: Mitogen-activated protein kinase; PKC: protein kinase C].](/paper-figures/65b50af717f64f498dc2d3e183e32d62/unlocking-the-multifaceted-roles-of-glp-1-physiological-functions-and-figure-2.jpg)
![Fig. 3 Intracellular signaling through Gαs mediated by GLP-1R. [GLP-1R: Glucagon like peptide-1 receptor; ATP: adenosine triphosphate; cAMP: cyclic adenine monophosphate; Epac: exchange protein directly activated by cAMP; PKA: protein kinase A; ERK1/2: Extracellular signal-regulated kinase 1/2; AKT: protein kinase B; mTOR: Mammalian target of rapamycin; CREB: cAMP-response element binding protein].](/paper-figures/9657977171f74148b533a15906aa90d1/unlocking-the-multifaceted-roles-of-glp-1-physiological-functions-and-figure-3.jpg)
![Fig. 4 GLP-1R: The Key to Unlocking Weight Loss? Exploring Potential Mechanisms [2].](/paper-figures/ac3b98a069bb4ef5b524170ce758b8dc/unlocking-the-multifaceted-roles-of-glp-1-physiological-functions-and-figure-4.jpg)
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“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]
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“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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Metadata
- 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 › Endocrinology, Diabetes and Metabolism › 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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