Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1.

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.

• Authors: Daniel J Drucker
• Journal: Cell metabolism (Cell Metab) Vol. 27 Issue 4 Pg. 740-756 (04 03 2018) ISSN: 1932-7420 [Electronic] United States
• PMID: 29617641 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Blood Glucose
• Glucagon-Like Peptide-1 Receptor
• Hypoglycemic Agents
• Insulin
• Glucagon-Like Peptide 1

Topics

• Animals
• Blood Glucose (drug effects)
• Diabetes Mellitus, Type 1 (therapy)
• Diabetes Mellitus, Type 2 (therapy)
• Eating (drug effects)
• Glucagon-Like Peptide 1 (adverse effects, pharmacology, therapeutic use)
• Glucagon-Like Peptide-1 Receptor (agonists, physiology)
• Humans
• Hypoglycemic Agents (therapeutic use)
• Insulin (metabolism)
• Mice
• Obesity (therapy)
• Rats
• Weight Gain (drug effects)