title: Central nervous insulin administration does not potentiate the acute glucoregulatory impact of concurrent mild hyperinsulinemia.
abstract: Experiments in rodents suggest that hypothalamic insulin signaling essentially contributes to the acute control of peripheral glucose homeostasis. Against this background, we investigated in healthy humans whether intranasal (IN) insulin, which is known to effectively reach the brain compartment, impacts systemic glucose metabolism. Twenty overnight-fasted healthy, normal-weight men were IN administered 210 and 420 international units [IU] (10 and 20 IU every 15 min) of the insulin analog aspart (ins-asp) and placebo, respectively, during experimental sessions lasting 6 h. The use of ins-asp rather than human insulin enabled us to disentangle exogenous and endogenous insulin kinetics. IN insulin dose-dependently decreased plasma glucose concentrations while reducing C-peptide and attenuating endogenous insulin levels. However, we also observed a slight dose-dependent permeation of ins-asp into the circulation. In control experiments mimicking the systemic but not the central nervous uptake of the IN 210 IU dose via intravenous infusion of ins-asp at a dose of 0.12 IU/kg/24 h (n = 10), we obtained essentially identical effects on fasting plasma glucose concentrations. This pattern indicates that sustained IN insulin administration to the human brain to enhance central nervous insulin signaling does not acutely alter systemic glucose homeostasis beyond effects accounted for by concurrent mild hyperinsulinemia.
authors.affiliation: Department of Neuroendocrinology, University of Lübeck, Lübeck, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Ott
authors.affiliation: Department of Internal Medicine I, University of Lübeck, Lübeck, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Lehnert
authors.affiliation: Department of Neuroendocrinology, University of Lübeck, Lübeck, Germany.
authors.forename: Josefine
authors.initials: J
authors.lastname: Staub
authors.affiliation: Department of Neuroendocrinology, University of Lübeck, Lübeck, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Wönne
authors.affiliation: Institute for Medical Psychology and Behavioral Neurobiology, University of Tübingen, Tübingen, Germany German Center for Diabetes Research, Tübingen, Germany Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen (IDM), Tübingen, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Born
authors.affiliation: Institute for Medical Psychology and Behavioral Neurobiology, University of Tübingen, Tübingen, Germany German Center for Diabetes Research, Tübingen, Germany Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen (IDM), Tübingen, Germany manfred.hallschmid@uni-tuebingen.de.
authors.forename: Manfred
authors.initials: M
authors.lastname: Hallschmid
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000187:drug effects; D002096:C-Peptide / Q000378:metabolism; D005215:Fasting / Q000097:blood; D005260:Female; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood* / Q000139:chemically induced*; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism* / Q000627:therapeutic use*; D008297:Male; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin