GLP ‐1 receptor activated insulin secretion from pancreatic β‐cells: mechanism and glucose dependence
Open accessAbstract
The major goal in the treatment of type 2 diabetes mellitus is to control the hyperglycaemia characteristic of the disease. However, treatment with common therapies such as insulin or insulinotrophic sulphonylureas ( SU ), while effective in reducing hyperglycaemia, may impose a greater risk of hypoglycaemia, as neither therapy is self‐regulated by ambient blood glucose concentrations. Hypoglycaemia has been associated with adverse physical and psychological outcomes and may contribute to negative cardiovascular events; hence minimization of hypoglycaemia risk is clinically advantageous. Stimulation of insulin secretion from pancreatic β‐cells by glucagon‐like peptide 1 receptor ( GLP‐1R ) agonists is known to be glucose‐dependent. GLP‐1R agonists potentiate glucose‐stimulated insulin secretion and have little or no activity on insulin secretion in the absence of elevated blood glucose concentrations. This ‘glucose‐regulated’ activity of GLP‐1R agonists makes them useful and potentially safer therapeutics for overall glucose control compared to non‐regulated therapies; hyperglycaemia can be reduced with minimal hypoglycaemia. While the inherent mechanism of action of GLP‐1R agonists mediates their glucose dependence, studies in rats suggest that SUs may uncouple this dependence. This hypothesis is supported by clinical studies showing that the majority of events of hypoglycaemia in patients treated with GLP‐1R agonists occur in patients treated with a concomitant SU . This review aims to discuss the current understanding of the mechanisms by which GLP ‐1R signalling promotes insulin secretion from pancreatic β‐cells via a glucose‐dependent process.
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Metformin primarily reduces hepatic glucose production, while GLP-1RAs enhance insulin secretion in response to meals.
“Metformin primarily reduces hepatic glucose production, while GLP-1RAs enhance insulin secretion in response to meals20–22.”
From Efficacy and safety of GLP-1 receptor agonists on weight management and metabolic parameters in PCOS women: a meta-analysis of randomized controlled trials (2025) · cites this paper as [22]
The Introduction (page unavailable) says GLP-1R agonists promote insulin secretion when blood glucose is elevated and describes GLP-1 release in response to ingested nutrients, supporting the meal-related portion of the claim. The paper does not state that metformin primarily reduces hepatic glucose production; its mentions of metformin concern combination therapy. (LLM, conf=0.87)
Experimental — accuracy not yet measuredGLP-1RAs decrease blood glucose levels, but they do not cause hypoglycemia.
“The GLP-1RAs decrease blood glucose levels, but they do not cause hypoglycemia [68].”
From The Role of Glp-1 Receptor Agonists in Insulin Resistance with Concomitant Obesity Treatment in Polycystic Ovary Syndrome (2022) · cites this paper as [68]
GLP-1 binds to insulin receptors on beta cells and stimulates insulin secretion.
“This hormone binds to insulin receptors on the beta cells and stimulates insulin secretion [67,68,69].”
From The Role of Glp-1 Receptor Agonists in Insulin Resistance with Concomitant Obesity Treatment in Polycystic Ovary Syndrome (2022) · cites this paper as [68]
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“GLP-1 stimulates insulin secretion from the pancreatic beta-cells under hyperglycemic conditions and reduces glucagon secretion from the alfa-cells recovering insulin sensitivity and enhancing glycemic homeostasis (Meloni et al., 2013; Katsurada and Yada, 2016).”
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Identifying crop variants with high resistant starch content to maintain healthy glucose homeostasis
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- Authors
- Meloni, A. R., DeYoung, M. B., Lowe, C., & Parkes, D. G.
- Affiliations
- Amylin Pharmaceuticals, Inc. San Diego CA USA
- Corresponding author
- Meloni, A. R.
- ORCID
- Meloni, A. R.
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2012-08
- Volume
- 15
- Issue
- 1
- Pages
- 15-27
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- PMC
- PMC3556522
- OpenAlex
- W2060476230
- Cited by
- 407
- References
- 99
- Citations by year
- 2026: 52 · 2025: 48 · 2024: 32 · 2023: 26 · 2022: 35 · 2021: 41 · 2020: 30 · 2019: 24 · 2018: 29 · 2017: 26 · 2016: 22 · 2015: 18 · 2014: 11 · 2013: 11 · 2012: 2
- FWCI
- 2.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes Obesity and Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- GLP-1 receptor agonists, insulin secretion, pancreatic beta cells, glucose-dependent insulin secretion, sulfonylureas, hypoglycemia, type 2 diabetes, glucose-stimulated insulin secretion
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Insulin Secretion, Blood Glucose, Diabetes Mellitus, Type 2, Female, Glycated Hemoglobin, Humans, Hyperglycemia, Insulin, Male, Receptors, Glucagon, Insulin-Secreting Cells, Dipeptidyl-Peptidase IV Inhibitors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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