title: Dissociation of GLP-1 and insulin association with food processing in the brain: GLP-1 sensitivity despite insulin resistance in obese humans.
abstract: OBJECTIVE
  Glucagon-like peptide-1 (GLP-1) is released into the bloodstream after food intake. In addition to stimulating insulin release, it causes satiety and contributes to the termination of food intake. In this study, we investigated whether endogenous GLP-1 affects food-related brain activity and hunger.
  
  
  METHODS
  Twenty-four volunteers (12 lean; 12 obese) underwent a 75 g oral glucose tolerance test that promotes GLP-1 secretion. Food cue-induced brain activity was assessed by functional magnetic resonance imaging and GLP-1 concentrations were measured before, 30, and 120 min after glucose intake.
  
  
  RESULTS
  The significant increase in GLP-1 levels negatively correlated with a change in the food cue-induced brain activity in the orbitofrontal cortex, a major reward area. This association was independent of simultaneous alterations in insulin and glucose concentrations. The association was present in lean and overweight participants. By contrast, postprandial insulin changes were associated with orbitofrontal activations in lean individuals only.
  
  
  CONCLUSIONS
  The postprandial release of GLP-1 might alter reward processes in the orbitofrontal cortex and might thereby support the termination of food intake and reduce hunger. While obese persons showed brain insulin resistance, no GLP-1 resistance was observed. Our study provides novel insight into the central regulation of food intake by the incretin hormone GLP-1.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard Karls University Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD e.V.), Tübingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Heni
authors.affiliation: Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD e.V.), Tübingen, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Kullmann
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Baptist
authors.initials: B
authors.lastname: Gallwitz
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard Karls University Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD e.V.), Tübingen, Germany.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Häring
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard Karls University Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD e.V.), Tübingen, Germany.
authors.forename: Hubert
authors.initials: H
authors.lastname: Preissl
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard Karls University Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD e.V.), Tübingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Fritsche
keywords: Brain; Brain insulin resistance; Glucagon-like peptide-1; Incretin; Orbitofrontal cortex; fMRI