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Diabetologia
Published in: Diabetologia 6/2012

01-06-2012 | Article

Nasal insulin changes peripheral insulin sensitivity simultaneously with altered activity in homeostatic and reward-related human brain regions

Authors: M. Heni, S. Kullmann, C. Ketterer, M. Guthoff, K. Linder, R. Wagner, K. T. Stingl, R. Veit, H. Staiger, H.-U. Häring, H. Preissl, A. Fritsche

Published in: Diabetologia | Issue 6/2012

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Abstract

Aims/hypothesis

Impaired insulin sensitivity is a major factor leading to type 2 diabetes. Animal studies suggest that the brain is involved in the regulation of insulin sensitivity. We investigated whether insulin action in the human brain regulates peripheral insulin sensitivity and examined which brain areas are involved.

Methods

Insulin and placebo were given intranasally. Plasma glucose, insulin and C-peptide were measured in 103 participants at 0, 30 and 60 min. A subgroup (n = 12) was also studied with functional MRI, and blood sampling at 0, 30 and 120 min. For each time-point, the HOMA of insulin resistance (HOMA-IR) was calculated as an inverse estimate of peripheral insulin sensitivity.

Results

Plasma insulin increased and subsequently decreased. This excursion was accompanied by slightly decreased plasma glucose, resulting in an initially increased HOMA-IR. At 1 h after insulin spray, the HOMA-IR subsequently decreased and remained lower up to 120 min. An increase in hypothalamic activity was observed, which correlated with the increased HOMA-IR at 30 min post-spray. Activity in the putamen, right insula and orbitofrontal cortex correlated with the decreased HOMA-IR at 120 min post-spray.

Conclusions/interpretation

Central insulin action in specific brain areas, including the hypothalamus, may time-dependently regulate peripheral insulin sensitivity. This introduces a potential novel mechanism for the regulation of peripheral insulin sensitivity and underlines the importance of cerebral insulin action for the whole organism.
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Metadata
Title
Nasal insulin changes peripheral insulin sensitivity simultaneously with altered activity in homeostatic and reward-related human brain regions
Authors
M. Heni
S. Kullmann
C. Ketterer
M. Guthoff
K. Linder
R. Wagner
K. T. Stingl
R. Veit
H. Staiger
H.-U. Häring
H. Preissl
A. Fritsche
Publication date
01-06-2012
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 6/2012
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-012-2528-y

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