title: The role of glucagon-like peptide-1 impairment in obesity and potential therapeutic implications.
abstract: The hormone glucagon-like peptide-1 (GLP-1) is released from the gut in response to food intake. It acts as a satiety signal, leading to reduced food intake, and also as a regulator of gastric emptying. Furthermore, GLP-1 functions as an incretin hormone, stimulating insulin release and inhibiting glucagon secretion from the pancreas in response to food ingestion. Evidence suggests that the action or effect of GLP-1 may be impaired in obese subjects, even in those with normal glucose tolerance. GLP-1 impairment may help explain the increased gastric emptying and decreased satiety signalling seen in obesity. Incretin impairment, probably associated with reduced insulinotropic potency of GLP-1, is also characteristic of type 2 diabetes (T2D). Therefore, it is possible that incretin impairment may contribute to the pathophysiological bridge between obesity and T2D. This review summarises current knowledge about the pathophysiology and consequences of GLP-1 and incretin impairment in obesity, and examines the evidence for an incretin-related link between obesity and T2D. It also considers the current literature surrounding the novel use of GLP-1 receptor agonists as a treatment for obesity in patients with normoglycaemia, prediabetes and T2D.
authors.affiliation: Department of Endocrinology, Hvidovre University Hospital, Hvidovre, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Madsbad
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000378:metabolism*; D005746:Gastric Emptying / Q000187:drug effects; D005769:Gastrointestinal Motility; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D054795:Incretins / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D009765:Obesity / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D018027:Receptors, Glucagon / Q000819:agonists / Q000378:metabolism*; D012527:Satiation / Q000187:drug effects
chemical_list: D001786:Blood Glucose; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D054795:Incretins; D007328:Insulin; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1
keywords: GLP-1; obesity therapy; type 2 diabetes