추천 논문

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

https://www.cell.com/cell-metabolism/fulltext/S1550-4131(18)30179-7?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1550413118301797%3Fshowall%3Dtrue

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

incretin

diabetes

obesity

cardiovascular disease

inflammation

metabolism

G protein-coupled receptor

drug

hypertension

body weight