title: Decreased Hypothalamic Glucagon-Like Peptide-1 Receptor Expression in Type 2 Diabetes Patients.
abstract: Glucagon-like peptide-1 (GLP-1) and GLP-1 receptor agonist treatment in type 2 diabetes (T2DM) reduce blood glucose and food intake. It has been suggested that these effects are partly mediated through central GLP-1 receptors (GLP-1Rs). The rodent and nonhuman primate hypothalamus show clear GLP-1R expression. However, a detailed description of GLP-1R expression in the human hypothalamus is lacking, and it is unknown whether this expression is altered in T2DM patients.
  
  
  
  The objective of the study was to investigate the GLP-1R distribution in the human postmortem hypothalamus and to determine whether hypothalamic GLP-1R expression is altered in T2DM patients.
  
  
  
  We investigated the distribution of GLP-1R expression throughout the human hypothalamus by means of in situ hybridization. We also performed quantifications of GLP-1R mRNA expression in two hypothalamic nuclei (ie, the paraventricular nucleus [PVN] and infundibular nucleus [IFN]), comparing patients with T2DM and control subjects.
  
  
  
  We found that GLP-1R mRNA was expressed in a number of hypothalamic nuclei including the PVN and the IFN, both involved in the regulation of energy metabolism. We observed sporadic colocalization of the GLP-1R in the IFN with the orgexigenic neuropeptide Y, agouti-related peptide, or proopiomelanocortin transcripts. Comparison of GLP-1R mRNA in the PVN and IFN between T2DM patients and control subjects revealed a decreased expression in T2DM patients.
  
  
  
  Our studies show that GLP-1R is widely expressed throughout the human hypothalamus. The decreased expression of GLP-1R in the PVN and IFN of T2DM patients may be related to the dysregulation of feeding behavior and glucose homeostasis in T2DM.
authors.affiliation: Diabetes Center and Department of Internal Medicine (J.S.t.K., L.v.B., R.G.I., M.D.), VU University Medical Center, 1007 MB Amsterdam, The Netherlands; Amsterdam Brain and Cognition Center (R.B., A.A.) and Department of Endocrinology and Metabolism (S.E.l.F.), Academic Medical Center, University of Amsterdam, 1100 DE Amsterdam, The Netherlands; and Department of Neuropsychiatric Disorders (D.F.S.), Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, 1105 BA Amsterdam, The Netherlands.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Ten Kulve
authors.affiliation: Diabetes Center and Department of Internal Medicine (J.S.t.K., L.v.B., R.G.I., M.D.), VU University Medical Center, 1007 MB Amsterdam, The Netherlands; Amsterdam Brain and Cognition Center (R.B., A.A.) and Department of Endocrinology and Metabolism (S.E.l.F.), Academic Medical Center, University of Amsterdam, 1100 DE Amsterdam, The Netherlands; and Department of Neuropsychiatric Disorders (D.F.S.), Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, 1105 BA Amsterdam, The Netherlands.
authors.forename: Liselotte
authors.initials: L
authors.lastname: van Bloemendaal
authors.affiliation: Diabetes Center and Department of Internal Medicine (J.S.t.K., L.v.B., R.G.I., M.D.), VU University Medical Center, 1007 MB Amsterdam, The Netherlands; Amsterdam Brain and Cognition Center (R.B., A.A.) and Department of Endocrinology and Metabolism (S.E.l.F.), Academic Medical Center, University of Amsterdam, 1100 DE Amsterdam, The Netherlands; and Department of Neuropsychiatric Disorders (D.F.S.), Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, 1105 BA Amsterdam, The Netherlands.
authors.forename: Rawien
authors.initials: R
authors.lastname: Balesar
authors.affiliation: Diabetes Center and Department of Internal Medicine (J.S.t.K., L.v.B., R.G.I., M.D.), VU University Medical Center, 1007 MB Amsterdam, The Netherlands; Amsterdam Brain and Cognition Center (R.B., A.A.) and Department of Endocrinology and Metabolism (S.E.l.F.), Academic Medical Center, University of Amsterdam, 1100 DE Amsterdam, The Netherlands; and Department of Neuropsychiatric Disorders (D.F.S.), Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, 1105 BA Amsterdam, The Netherlands.
authors.forename: Richard G
authors.initials: RG
authors.lastname: IJzerman
authors.affiliation: Diabetes Center and Department of Internal Medicine (J.S.t.K., L.v.B., R.G.I., M.D.), VU University Medical Center, 1007 MB Amsterdam, The Netherlands; Amsterdam Brain and Cognition Center (R.B., A.A.) and Department of Endocrinology and Metabolism (S.E.l.F.), Academic Medical Center, University of Amsterdam, 1100 DE Amsterdam, The Netherlands; and Department of Neuropsychiatric Disorders (D.F.S.), Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, 1105 BA Amsterdam, The Netherlands.
authors.forename: Dick F
authors.initials: DF
authors.lastname: Swaab
authors.affiliation: Diabetes Center and Department of Internal Medicine (J.S.t.K., L.v.B., R.G.I., M.D.), VU University Medical Center, 1007 MB Amsterdam, The Netherlands; Amsterdam Brain and Cognition Center (R.B., A.A.) and Department of Endocrinology and Metabolism (S.E.l.F.), Academic Medical Center, University of Amsterdam, 1100 DE Amsterdam, The Netherlands; and Department of Neuropsychiatric Disorders (D.F.S.), Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, 1105 BA Amsterdam, The Netherlands.
authors.forename: Michaela
authors.initials: M
authors.lastname: Diamant
authors.affiliation: Diabetes Center and Department of Internal Medicine (J.S.t.K., L.v.B., R.G.I., M.D.), VU University Medical Center, 1007 MB Amsterdam, The Netherlands; Amsterdam Brain and Cognition Center (R.B., A.A.) and Department of Endocrinology and Metabolism (S.E.l.F.), Academic Medical Center, University of Amsterdam, 1100 DE Amsterdam, The Netherlands; and Department of Neuropsychiatric Disorders (D.F.S.), Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, 1105 BA Amsterdam, The Netherlands.
authors.forename: Susanne E
authors.initials: SE
authors.lastname: la Fleur
authors.affiliation: Diabetes Center and Department of Internal Medicine (J.S.t.K., L.v.B., R.G.I., M.D.), VU University Medical Center, 1007 MB Amsterdam, The Netherlands; Amsterdam Brain and Cognition Center (R.B., A.A.) and Department of Endocrinology and Metabolism (S.E.l.F.), Academic Medical Center, University of Amsterdam, 1100 DE Amsterdam, The Netherlands; and Department of Neuropsychiatric Disorders (D.F.S.), Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, 1105 BA Amsterdam, The Netherlands.
authors.forename: Anneke
authors.initials: A
authors.lastname: Alkemade
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D054369:Agouti-Related Protein / Q000235:genetics / Q000378:metabolism; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D000067757:Glucagon-Like Peptide-1 Receptor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism
chemical_list: C515198:AGRP protein, human; D054369:Agouti-Related Protein; D000067757:Glucagon-Like Peptide-1 Receptor; D009478:Neuropeptide Y; D011333:Pro-Opiomelanocortin