Original Abstract

Secreted by enteroendocrine cells in the gastrointestinal tract, glucagon-like peptide-1 (GLP-1) is pivotal in the management of glycemic variability, as it promotes insulin secretion while concurrently suppressing glucagon release. This review investigates the neural circuits activated by both endogenous and pharmacological forms of GLP-1, with particular attention to the important cell types that express GLP-1 receptors (GLP-1R) and the pathways that relay both metabolic and non-glycemic signals linked to GLP-1. The examination includes the effects of GLP-1 on the benefits and adverse outcomes related to bariatric surgery, as well as its influence on islet function, appetite regulation, inflammation, and cardiovascular health. This review introduces both established and new concepts, identifies outstanding questions, and outlines future challenges in the development and optimization of GLP-1R agonists for the management of cardiovascular disease. The role of GLP-1 in enhancing endurance, muscle recovery, fiber type distribution, muscle mass, and energy efficiency is well-documented. Furthermore, GLP-1 influences various physiological components, including bile acids, short-chain fatty acids, L cells, and G-protein-coupled receptors. Increased levels of GLP-1 due to overexpression lead to higher glycogen concentrations, the development of endurance-oriented muscle fibers, augmented mitochondrial content, and improved glucose uptake in skeletal muscle. Exercise training has been shown to elevate GLP-1 levels, which may be beneficial for those suffering from metabolic syndrome. Nonetheless, additional research is necessary to clarify how exercise promotes GLP-1 secretion in individuals with cardiovascular diseases.