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Ott, V.* ; Lehnert, H.* ; Staub, J.* ; Wönne, K.* ; Born, J. ; Hallschmid, M.

Central nervous insulin administration does not potentiate the acute glucoregulatory impact of concurrent mild hyperinsulinemia.

Diabetes 64, 760-765 (2015)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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 IU (10 and 20 IU every 15 min) of the insulin analogue 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 IV infusion of ins-asp at a dose of 0.12 mIU/kg/24h (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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Hepatic Glucose-production; Intranasal Insulin; Cerebrospinal-fluid; Human Brain; Humans; Men; Sensitivity; Secretion; Memory; Dogs
ISSN (print) / ISBN 0012-1797
e-ISSN 1939-327X
Journal Diabetes
Quellenangaben Volume: 64, Issue: 3, Pages: 760-765 Article Number: , Supplement: ,
Publisher American Diabetes Association
Publishing Place Alexandria, VA.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research and Metabolic Diseases (IDM)
German Center for Diabetes Reseach (DZD)