title: Ghrelin, CCK, GLP-1, and PYY(3-36): Secretory Controls and Physiological Roles in Eating and Glycemia in Health, Obesity, and After RYGB.
abstract: The efficacy of Roux-en-Y gastric-bypass (RYGB) and other bariatric surgeries in the management of obesity and type 2 diabetes mellitus and novel developments in gastrointestinal (GI) endocrinology have renewed interest in the roles of GI hormones in the control of eating, meal-related glycemia, and obesity. Here we review the nutrient-sensing mechanisms that control the secretion of four of these hormones, ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and peptide tyrosine tyrosine [PYY(3-36)], and their contributions to the controls of GI motor function, food intake, and meal-related increases in glycemia in healthy-weight and obese persons, as well as in RYGB patients. Their physiological roles as classical endocrine and as locally acting signals are discussed. Gastric emptying, the detection of specific digestive products by small intestinal enteroendocrine cells, and synergistic interactions among different GI loci all contribute to the secretion of ghrelin, CCK, GLP-1, and PYY(3-36). While CCK has been fully established as an endogenous endocrine control of eating in healthy-weight persons, the roles of all four hormones in eating in obese persons and following RYGB are uncertain. Similarly, only GLP-1 clearly contributes to the endocrine control of meal-related glycemia. It is likely that local signaling is involved in these hormones' actions, but methods to determine the physiological status of local signaling effects are lacking. Further research and fresh approaches are required to better understand ghrelin, CCK, GLP-1, and PYY(3-36) physiology; their roles in obesity and bariatric surgery; and their therapeutic potentials.
authors.affiliation: University of Adelaide Discipline of Medicine and National Health and Medical Research Council of Australia Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide, Australia; DSM Nutritional Products, R&D Human Nutrition and Health, Basel, Switzerland; Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland; Department of Biomedicine and Division of Gastroenterology, University Hospital Basel, Basel, Switzerland; and Department of Psychiatry, Weill Medical College of Cornell University, New York, New York.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Steinert
authors.affiliation: University of Adelaide Discipline of Medicine and National Health and Medical Research Council of Australia Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide, Australia; DSM Nutritional Products, R&D Human Nutrition and Health, Basel, Switzerland; Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland; Department of Biomedicine and Division of Gastroenterology, University Hospital Basel, Basel, Switzerland; and Department of Psychiatry, Weill Medical College of Cornell University, New York, New York.
authors.forename: Christine
authors.initials: C
authors.lastname: Feinle-Bisset
authors.affiliation: University of Adelaide Discipline of Medicine and National Health and Medical Research Council of Australia Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide, Australia; DSM Nutritional Products, R&D Human Nutrition and Health, Basel, Switzerland; Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland; Department of Biomedicine and Division of Gastroenterology, University Hospital Basel, Basel, Switzerland; and Department of Psychiatry, Weill Medical College of Cornell University, New York, New York.
authors.forename: Lori
authors.initials: L
authors.lastname: Asarian
authors.affiliation: University of Adelaide Discipline of Medicine and National Health and Medical Research Council of Australia Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide, Australia; DSM Nutritional Products, R&D Human Nutrition and Health, Basel, Switzerland; Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland; Department of Biomedicine and Division of Gastroenterology, University Hospital Basel, Basel, Switzerland; and Department of Psychiatry, Weill Medical College of Cornell University, New York, New York.
authors.forename: Michael
authors.initials: M
authors.lastname: Horowitz
authors.affiliation: University of Adelaide Discipline of Medicine and National Health and Medical Research Council of Australia Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide, Australia; DSM Nutritional Products, R&D Human Nutrition and Health, Basel, Switzerland; Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland; Department of Biomedicine and Division of Gastroenterology, University Hospital Basel, Basel, Switzerland; and Department of Psychiatry, Weill Medical College of Cornell University, New York, New York.
authors.forename: Christoph
authors.initials: C
authors.lastname: Beglinger
authors.affiliation: University of Adelaide Discipline of Medicine and National Health and Medical Research Council of Australia Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide, Australia; DSM Nutritional Products, R&D Human Nutrition and Health, Basel, Switzerland; Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland; Department of Biomedicine and Division of Gastroenterology, University Hospital Basel, Basel, Switzerland; and Department of Psychiatry, Weill Medical College of Cornell University, New York, New York.
authors.forename: Nori
authors.initials: N
authors.lastname: Geary
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D002766:Cholecystokinin / Q000378:metabolism*; D004435:Eating / Q000502:physiology; D015390:Gastric Bypass; D054439:Ghrelin / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D006801:Humans; D009765:Obesity / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D019894:Peptide YY / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D054439:Ghrelin; D010446:Peptide Fragments; D019894:Peptide YY; C061785:peptide YY (3-36); D052216:Glucagon-Like Peptide 1; D002766:Cholecystokinin