Abstract
Glucagon-like peptide-1 (GLP-1) released from gut enteroendocrine cells controls meal-related glycemic excursions through augmentation of insulin and inhibition of glucagon secretion. GLP-1 also inhibits gastric emptying and food intake, actions maximizing nutrient absorption while limiting weight gain. Here I review the circuits engaged by endogenous versus pharmacological GLP-1 action, highlighting key GLP-1 receptor (GLP-1R)-positive cell types and pathways transducing metabolic and non-glycemic GLP-1 signals. The role(s) of GLP-1 in the benefits and side effects associated with bariatric surgery are discussed and actions of GLP-1 controlling islet function, appetite, inflammation, and cardiovascular pathophysiology are highlighted. Refinement of the risk-versus-benefit profile of GLP-1-based therapies for the treatment of diabetes and obesity has stimulated development of orally bioavailable agonists, allosteric modulators, and unimolecular multi-agonists, all targeting the GLP-1R. This review highlights established and emerging concepts, unanswered questions, and future challenges for development and optimization of GLP-1R agonists in the treatment of metabolic disease.
Keywords
Gastric emptyingGlucagon-like peptide-1Enteroendocrine cellAppetiteGlycemicMedicineType 2 diabetesGlucagon-like peptide-2Glucagon-like peptide 1 receptorPharmacologyReceptorDiabetes mellitusEndocrinologyBioinformaticsInternal medicineBiologyEndocrine systemAgonistPeptideHormoneBiochemistryStomach
MeSH Terms
AnimalsBlood GlucoseDiabetes MellitusType 1Diabetes MellitusType 2EatingGlucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorHumansHypoglycemic AgentsInsulinMiceObesityRatsWeight GainGlucagon-Like Peptide-1 Receptor Agonists
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Publication Info
- Year
- 2018
- Type
- review
- Volume
- 27
- Issue
- 4
- Pages
- 740-756
- Citations
- 1589
- Access
- Closed
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Cite This
Daniel J. Drucker
(2018).
Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1.
Cell Metabolism
, 27
(4)
, 740-756.
https://doi.org/10.1016/j.cmet.2018.03.001
Identifiers
- DOI
- 10.1016/j.cmet.2018.03.001
- PMID
- 29617641