title: Evolving Concepts and Translational Relevance of Enteroendocrine Cell Biology.
abstract: BACKGROUND
  Classical enteroenteroendocrine cell (EEC) biology evolved historically from identification of scattered hormone-producing endocrine cells within the epithelial mucosa of the stomach, small and large intestine. Purification of functional EEC hormones from intestinal extracts, coupled with molecular cloning of cDNAs and genes expressed within EECs has greatly expanded the complexity of EEC endocrinology, with implications for understanding the contribution of EECs to disease pathophysiology.
  
  
  METHODS
  Pubmed searches identified manuscripts highlighting new concepts illuminating the molecular biology, classification and functional role(s) of EECs and their hormonal products.
  
  
  RESULTS
  Molecular interrogation of EECs has been transformed over the past decade, raising multiple new questions that challenge historical concepts of EEC biology. Evidence for evolution of the EEC from a unihormonal cell type with classical endocrine actions, to a complex plurihormonal dynamic cell with pleiotropic interactive functional networks within the gastrointestinal mucosa is critically assessed. We discuss gaps in understanding how EECs sense and respond to nutrients, cytokines, toxins, pathogens, the microbiota, and the microbial metabolome, and highlight the expanding translational relevance of EECs in the pathophysiology and therapy of metabolic and inflammatory disorders.
  
  
  CONCLUSIONS
  The EEC system represents the largest specialized endocrine network in human physiology, integrating environmental and nutrient cues, enabling neural and hormonal control of metabolic homeostasis. Updating EEC classification systems will enable more accurate comparative analyses of EEC subpopulations and endocrine networks in multiple regions of the gastrointestinal tract.
authors.affiliation: Department of Medicine, Mt. Sinai Hospital, University of Toronto and the Lunenfeld-Tanenbaum Research Institute, Toronto, Canada M5G 1X5.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Drucker
mesh_terms: D019858:Enteroendocrine Cells / Q000502:physiology*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007414:Intestinal Neoplasms / Q000209:etiology; D018358:Neuroendocrine Tumors / Q000209:etiology; D009626:Terminology as Topic
chemical_list: D052216:Glucagon-Like Peptide 1