title: Hypothalamic insulin responsiveness is associated with pancreatic insulin secretion in humans.
abstract: BACKGROUND
  Activity of the hypothalamus - the major brain area controlling peripheral metabolism - is specifically modulated by insulin. Research in animals suggests that brain insulin action influences pancreatic insulin secretion.
  
  
  OBJECTIVE
  We investigated the association between hypothalamic insulin sensitivity and pancreatic insulin secretion in humans.
  
  
  METHODS
  This was a clinical-experimental trial in an university hospital setting.
  
  
  METHODS
  48 healthy volunteers (21 women and 27 men) were included.
  
  
  METHODS
  Insulin sensitivity of the hypothalamus was quantified by cerebral blood flow (CBF) using MRI in combination with intranasal insulin administration. On a different day, a 75g oral glucose tolerance test with glucose, insulin, and C-peptide levels measured at five time points was performed. Three established insulin secretion indices (insulinogenic index [IGI], corrected insulin response [CIR], and AUCC-peptide0-30/AUCglucose0-30) were then analyzed for correlations with hypothalamic insulin sensitivity independent of whole-body insulin sensitivity.
  
  
  RESULTS
  Hypothalamic insulin sensitivity showed a significant association with all three investigated insulin secretion indices (IGI p=0.0043; CIR p=0.06; AUCCpep0-30/AUCgluc0-30p=0.0179). Participants with a strong hypothalamic insulin effect (i.e. decreased CBF after intranasal insulin administration) had lower insulin secretion during the OGTT, whereas participants with hypothalamic insulin resistance had substantially higher insulin secretion. No correlations with the occipital cortex, a control region, were detected.
  
  
  CONCLUSIONS
  Our data suggest that hypothalamic insulin resistance might contribute to pancreatic insulin hypersecretion. Alternatively, common pathogenetic mechanisms could introduce both brain insulin resistance and beta cell hypersecretion.
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: 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; 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. Electronic address: andreas.fritsche@med.uni-tuebingen.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Fritsche
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: Robert
authors.initials: R
authors.lastname: Wagner
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Sophia
authors.initials: S
authors.lastname: Schwab
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; Interfaculty Centre for Pharmacogenomics and Pharma Research at the Eberhard Karls University Tübingen, 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; Institute of Pharmaceutical Sciences, Department of Pharmacy and Biochemistry, Eberhard Karls University Tübingen, Tübingen, Germany; Interfaculty Centre for Pharmacogenomics and Pharma Research at the Eberhard Karls University Tübingen, Tübingen, Germany; Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Center Munich, German Research Center for Environmental Health (GmbH), Neuherberg, 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: Martin
authors.initials: M
authors.lastname: Heni
mesh_terms: D000328:Adult; D019540:Area Under Curve; D005260:Female; D005951:Glucose Tolerance Test; D064368:Healthy Volunteers; D006801:Humans; D007031:Hypothalamus / Q000000981:diagnostic imaging* / Q000187:drug effects; D007091:Image Processing, Computer-Assisted; D007328:Insulin / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging; D008297:Male; D009778:Occipital Lobe / Q000000981:diagnostic imaging; D010100:Oxygen / Q000097:blood; D011652:Pulmonary Circulation / Q000187:drug effects*; D055815:Young Adult
chemical_list: D007328:Insulin; D010100:Oxygen