title: GLP-1 and energy balance: an integrated model of short-term and long-term control.
abstract: Glucagon-like peptide 1 (GLP-1), a peptide secreted from the intestine in response to nutrient ingestion, is perhaps best known for its effect on glucose-stimulated insulin secretion. GLP-1 is also secreted from neurons in the caudal brainstem, and it is well-established that, in rodents, central administration of GLP-1 potently reduces food intake. Over the past decade, GLP-1 has emerged not only as an essential component of the system that regulates blood glucose levels but also as a viable therapeutic target for the treatment of type 2 diabetes mellitus. However, although GLP-1 receptor agonists are known to produce modest but statistically significant weight loss in patients with diabetes mellitus, our knowledge of how endogenous GLP-1 regulates food intake and body weight remains limited. The purpose of this Review is to discuss the evolution of our understanding of how endogenous GLP-1 modulates energy balance. Specifically, we consider contributions of both central and peripheral GLP-1 and propose an integrated model of short-term and long-term control of energy balance. Finally, we discuss this model with respect to current GLP-1-based therapies and suggest ongoing research in order to maximize the effectiveness of GLP-1-based treatment of obesity.
authors.affiliation: Department of Internal Medicine, University of Cincinnati, OH 45237, USA.
authors.forename: Jason G
authors.initials: JG
authors.lastname: Barrera
authors.forename: Darleen A
authors.initials: DA
authors.lastname: Sandoval
authors.forename: David A
authors.initials: DA
authors.lastname: D'Alessio
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Seeley
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000378:metabolism; D018027:Receptors, Glucagon / Q000819:agonists / Q000378:metabolism
chemical_list: D001786:Blood Glucose; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D007328:Insulin; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1