Evolutionarily, the intestine is the most ancient endocrine organ. Hormone production and release are strictly regulated in the enteroendocrine cells dispersed and organized in secreting microorgans in the entire length of the intestinal mucosa, in response to nutrient transient, microbiota products, and neuronal stimuli. The complex system linking intestinal hormones to their several organ and cellular targets not only regulates food intake and nutrient absorption but is pivotal for controlling metabolism and other systemic functions. This chapter presents the main hormones produced in the intestine, the mechanisms of their controlled secretion, and their functions. In particular, the coevolution of the members of the glucagon-like peptide hormones and their receptors and their molecular structures are discussed. Finally, the relevance of these molecules in the development and treatment of metabolic pathologies such as diabetes type 2 and obesity is introduced, focusing on the current use of synthetic agonists of these receptors and future applications of combined molecules to selectively improve obesity and diabetes therapy.
