Modulation of midbrain neurocircuitry by intranasal insulin
Open accessAbstract
Insulin modulates dopamine neuron activity in midbrain and affects processes underlying food intake behaviour, including impulsivity and reward processing. Here, we used intranasal administration and task-free functional MRI in humans to assess time- and dose-dependent effects of insulin on functional connectivity of the dopaminergic midbrain - and how these effects varied depending on systemic insulin sensitivity as measured by HOMA-IR. Specifically, we used a repeated-measures design with factors dose (placebo, 40 IU, 100 IU, 160 IU), time (7 time points during a 90 min post-intervention interval), and group (low vs. high HOMA-IR). A factorial analysis identified a three-way interaction (with whole-brain significance) with regard to functional connectivity between midbrain and the ventromedial prefrontal cortex. This interaction demonstrates that systemic insulin sensitivity modulates the temporal course and dose-dependent effects of intranasal insulin on midbrain functional connectivity. It suggests that altered insulin sensitivity may impact on dopaminergic projections of the midbrain and might underlie the dysregulation of reward-related and motivational behaviour in obesity and diabetes. Perhaps most importantly, the time courses of midbrain functional connectivity we present may provide useful guidance for the design of future human studies that utilize intranasal insulin administration.
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The used dose of 160 U resulted in substantial effects on brain activity, comparable to oral glucose ingestion, and has been widely used in previous trials on acute brain effects of insulin.
“Despite the lack of data on the exact amount of insulin reaching the brain, previous trials found that the used dose of 160 U resulted in substantial effects on brain activity6,7, comparable to oral glucose ingestion, and this dose has been widely used in previous trials on acute brain effects of insulin38.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [7]
The dose-dependent effect of IN insulin on functional connectivity of the midbrain to the ventromedial prefrontal cortex in humans depends on systemic insulin sensitivity rather than BMI.
“the dose-dependent effect of IN insulin on functional connectivity of the midbrain to the ventromedial prefrontal cortex in humans depends on systemic insulin sensitivity (rather than BMI).161”
From Intranasal insulin (2021) · cites this paper as [161]
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- Authors
- Edwin Thanarajah, S., Iglesias, S., Kuzmanovic, B., Rigoux, L., Stephan, K. E., Brüning, J. C., & Tittgemeyer, M.
- Affiliations
- University of Zurich (CH)
- Max Planck Institute for Metabolism Research (DE)
- Corresponding author
- Tittgemeyer, Marc
- ORCID
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2019-07
- Volume
- 194
- Pages
- 120-127
- ISSN
- 1053-8119 (ISSN-L)
- OpenAlex
- W2926816892
- Cited by
- 55
- References
- 71
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 6 · 2023: 6 · 2022: 11 · 2021: 10 · 2020: 4 · 2019: 1
- FWCI
- 3.10
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- NeuroImage (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by-nc-nd)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by-nc-nd)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by-nc-nd)
- ETH Zürich Research Collection
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- German Center for Diabetes Research
- German Research Foundation
- Transregional Collaborative Research Center
- University of Zurich
- René and Susanne Braginsky Foundation
- CRPP “Molecular Imaging”
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- intranasal insulin, midbrain, dopaminergic neurons, functional connectivity, ventromedial prefrontal cortex, insulin sensitivity, HOMA-IR, dose-dependent effects, time course, reward processing, impulsivity, obesity, diabetes mellitus
- MeSH terms
- Administration, Intranasal, Adult, Dose-Response Relationship, Drug, Humans, Hypoglycemic Agents, Insulin, Insulin Resistance, Magnetic Resonance Imaging, Male, Mesencephalon, Overweight
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