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Heni, M. ; Wagner, R. ; Willmann, C. ; Jaghutriz, B.A. ; Vosseler, A. ; Kübler, C. ; Hund, V.* ; Scheffler, K.* ; Peter, A. ; Häring, H.-U. ; Preissl, H. ; Kullmann, S. ; Fritsche, A.

Insulin action in the hypothalamus increases second phase insulin secretion in humans.

Neuroendocrinology 110, 929-937 (2020)
Verlagsversion Postprint DOI PMC
Open Access Green
Background:Animal studies and initial correlative data in humans indicate that insulin action in the brain may affect pancreatic insulin secretion. An important brain region for this process is the hypothalamus, an area that can develop insulin resistance.Methods:Fifteen young, healthy men (27 +/- 3 years) with a wide BMI spectrum (20-30 kg/m(2)) underwent 2 hyperglycemic clamps (target blood glucose: 10 mmol/L). In this double-blind study, subjects received 160 U of insulin or placebo as a nasal spray on 2 days in randomized order. On another day, insulin sensitivity of the hypothalamus was determined by functional magnetic resonance imaging.Results:Glucose levels were comparable on both study days. In the whole group, C-peptide levels were not significantly different between conditions. Though, there was a significant interaction between insulin sensitivity of the hypothalamus x nasal spray x time on C-peptide levels (p= 10(-6)). The group was therefore divided according to median hypothalamic insulin sensitivity. C-peptide concentrations were higher after intranasal insulin compared to placebo spray in the group with a strong hypothalamic insulin response (p< 0.0001, beta = 6.00 +/- 1.24) and lower in the brain insulin-resistant group (p= 0.005, beta = -2.68 +/- 0.95). Neither somatostatin nor glucagon kinetics was altered by the nasal spray.Conclusions:In participants with high hypothalamic insulin sensitivity, insulin action in the brain enhanced second-phase insulin secretion from pancreatic beta cells. This reaction could, for example, contribute to late postprandial glucose regulation by suppressing hepatic glucose production by portal venous insulin.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Hypothalamus ; Imaging ; Insulin Resistance ; Insulin Secretion ; Pancreas; Ventromedial Hypothalamus; Glucose; Obesity; Hyperinsulinemia; Overweight; Resistance; Glucagon; Sensitivity; System
Sprache englisch
Veröffentlichungsjahr 2020
Prepublished im Jahr 2019
HGF-Berichtsjahr 2019
ISSN (print) / ISBN 0028-3835
e-ISSN 1423-0194
Zeitschrift Neuroendocrinology
Quellenangaben Band: 110, Heft: 11-12, Seiten: 929-937 Artikelnummer: , Supplement: ,
Verlag Karger
Verlagsort Allschwilerstrasse 10, Ch-4009 Basel, Switzerland
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research and Metabolic Diseases (IDM)
POF Topic(s) 90000 - German Center for Diabetes Research
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-502400-001
Förderungen German Federal Ministry of Education and Research (BMBF)
DOI 10.1159/000504551
WOS ID WOS:000576042600004
PubMed ID 31689708
Erfassungsdatum 2020-01-13
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