Regulation of Glucose Homeostasis by GLP-1
Open accessAbstract
Glucagon-like peptide-1(7-36)amide (GLP-1) is a secreted peptide that acts as a key determinant of blood glucose homeostasis by virtue of its abilities to slow gastric emptying, to enhance pancreatic insulin secretion, and to suppress pancreatic glucagon secretion. GLP-1 is secreted from L cells of the gastrointestinal mucosa in response to a meal, and the blood glucose-lowering action of GLP-1 is terminated due to its enzymatic degradation by dipeptidyl-peptidase-IV (DPP-IV). Released GLP-1 activates enteric and autonomic reflexes while also circulating as an incretin hormone to control endocrine pancreas function. The GLP-1 receptor (GLP-1R) is a G protein-coupled receptor that is activated directly or indirectly by blood glucose-lowering agents currently in use for the treatment of type 2 diabetes mellitus (T2DM). These therapeutic agents include GLP-1R agonists (exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, and langlenatide) and DPP-IV inhibitors (sitagliptin, vildagliptin, saxagliptin, linagliptin, and alogliptin). Investigational agents for use in the treatment of T2DM include GPR119 and GPR40 receptor agonists that stimulate the release of GLP-1 from L cells. Summarized here is the role of GLP-1 to control blood glucose homeostasis, with special emphasis on the advantages and limitations of GLP-1-based therapeutics.
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GLP-1 is an incretin hormone that plays a pivotal role in the control of human blood glucose levels.
“GLP-1 is an incretin hormone that plays a pivotal role in the meticulous control of human blood glucose levels.”
From Glucagon-like peptide-1 receptor: mechanisms and advances in therapy (2024) · cites this paper as [33]
GLP-1RAs are a group of drugs that imitate the activity of the incretin hormone GLP-1 secreted in the distal part of the small intestine.
“The GLP-1RAs, also known as incretin mimetics, are a group of drugs that imitate the activity of the incretin hormone GLP-1 secreted in the distal part of the small intestine [67].”
From The Role of Glp-1 Receptor Agonists in Insulin Resistance with Concomitant Obesity Treatment in Polycystic Ovary Syndrome (2022) · cites this paper as [67]
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 [67]
GLP-1 receptor agonists act by glucose-dependent stimulation of insulin secretion in pancreatic beta cells and in many other mechanisms.
“They act by glucose-dependent stimulation of insulin secretion in pancreatic islets β-cells and in many other mechanisms [67].”
From The Role of Glp-1 Receptor Agonists in Insulin Resistance with Concomitant Obesity Treatment in Polycystic Ovary Syndrome (2022) · cites this paper as [67]
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References 283 · Cited by 287
- Authors
- Nadkarni, P., Chepurny, O. G., & Holz, G. G.
- Affiliations
- Joslin Diabetes Center (US)
- SUNY Upstate Medical University (US)
- State University of New York (US)
- Corresponding author
- Holz, George G.
- Venue
- Progress in Molecular Biology and Translational Science
- Publisher
- Elsevier
- Published
- 2014
- Volume
- 121
- Pages
- 23-65
- ISSN
- 1877-1173 (ISSN-L)
- PMC
- PMC4159612
- OpenAlex
- W140545298
- Cited by
- 287
- References
- 283
- Citations by year
- 2026: 21 · 2025: 36 · 2024: 36 · 2023: 28 · 2022: 29 · 2021: 28 · 2020: 20 · 2019: 26 · 2018: 16 · 2017: 8 · 2016: 21 · 2015: 12 · 2014: 5 · 2013: 1
- FWCI
- 37.55
- Type
- book chapter
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Progress in molecular biology and translational science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK045817, R01DK069575)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- glucagon-like peptide-1, glucose homeostasis, GLP-1 receptor, incretins, type 2 diabetes, GLP-1 receptor agonists, DPP-4 inhibitors, GPR119, GPR40, gastric emptying, insulin secretion, glucagon secretion, L cells, exenatide, sitagliptin
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Animals, Diabetes Mellitus, Type 2, Glucose, Homeostasis, Humans, Receptors, Glucagon, Insulin-Secreting Cells, Glucagon-Like Peptide 1
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