Role of glucagon-like peptide-1 in the pathogenesis and treatment of diabetes mellitus
Abstract
Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted from enteroendocrine L cells in response to ingested nutrients. The first recognized and most important action of GLP-1 is the potentiation of glucose-stimulated insulin secretion in beta-cells, mediated by activation of its seven transmembrane domain G-protein-coupled receptor. In addition to its insulinotropic actions, GLP-1 exerts islet-trophic effects by stimulating replication and differentiation and by decreasing apoptosis of beta-cells. The GLP-1 receptor is expressed in a variety of other tissues important for carbohydrate metabolism, including pancreatic alpha-cells, hypothalamus and brainstem, and proximal intestinal tract. GLP-1 also appears to exert important actions in liver, muscle and fat. Thus, GLP-1 suppresses glucagon secretion, promotes satiety, delays gastric emptying and stimulates peripheral glucose uptake. The impaired GLP-1 secretion observed in type 2 diabetes suggests that GLP-1 plays a role in the pathogenesis of this disorder. Thus, because of its multiple actions, GLP-1 is an attractive therapeutic target for the treatment of type 2 diabetes, and major interest has resulted in the development of a variety of GLP-1 receptor agonists for this purpose. Ongoing clinical trials have shown promising results and the first analogs of GLP-1 are expected to be available in the near future.
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In non-diabetic subjects, incretins are responsible for 50-70% of total insulin secreted after oral glucose.
“In non-diabetic subjects, Incretins are responsible for 50–70% of the total insulin secreted after oral glucose administration.[23–25]”
From Postprandial Reactive Hypoglycemia (2019) · cites this paper as [23]
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- Authors
- León, D. D. D., Crutchlow, M. F., Ham, J.-Y. N., & Stoffers, D. A.
- Affiliations
- Children's Hospital of Philadelphia (US)
- University of Pennsylvania Health System (US)
- Corresponding author
- Stoffers, Doris A.
- Venue
- The International Journal of Biochemistry & Cell Biology
- Publisher
- Elsevier BV
- Published
- 2006-05
- Volume
- 38
- Issue
- 5-6
- Pages
- 845-859
- ISSN
- 1357-2725 (ISSN-L)
- OpenAlex
- W2082763759
- Cited by
- 94
- References
- 23
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 5 · 2018: 1 · 2017: 5 · 2016: 4 · 2015: 4 · 2014: 1 · 2013: 5 · 2012: 6
- FWCI
- 0.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The International Journal of Biochemistry & Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- glucagon-like peptide-1, type 2 diabetes, incretins, GLP-1 receptor, glucose-stimulated insulin secretion, pancreatic beta cells, islet regeneration, GLP-1 receptor agonists, GLP-1 analogues, satiety, gastric emptying, glucagon secretion, diabetes pathogenesis, diabetes treatment
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Liraglutide, Exenatide, Amino Acid Sequence, Animals, Blood Glucose, Diabetes Mellitus, Diabetes Mellitus, Type 2, Homeostasis, Humans, Maleimides, Molecular Sequence Data, Nitriles, Peptides, Protease Inhibitors, Pyrrolidines, Venoms, Receptors, Glucagon, Dipeptidyl Peptidase 4, Glucagon-Like Peptide 1
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