Brain insulin responsiveness is linked to age and peripheral insulin sensitivity
Open accessAbstract
Aims: Insulin action in the brain influences cognitive processes, peripheral metabolism and eating behaviour. However, the influence of age and peripheral insulin sensitivity on brain insulin action remains unclear. Materials and Methods: We used intranasal administration of insulin and functional magnetic resonance imaging in a randomized, placebo‐controlled within‐subject design in 110 participants (54 women, body mass index 18‐49 kg/m 2 , age 21‐74 years). Cerebral blood flow was measured before and after nasal spray application to assess brain insulin action. Peripheral insulin sensitivity was assessed by a five‐point oral glucose tolerance test. Linear regressions were used to investigate associations between age and peripheral insulin sensitivity with brain insulin action in predefined region of interests (i.e. insulin‐sensitive brain regions). Results: We found significant negative associations between age and insulin action in the hippocampus (β = –0.215; p = .017) and caudate nucleus (β = –0.184; p = .047); and between peripheral insulin sensitivity and insulin action in the amygdala (β = –0.190, p = .023). Insulin action in the insular cortex showed an interaction effect between age and peripheral insulin sensitivity (β = –0.219 p = .005). Furthermore, women showed the strongest negative association between age and hippocampal insulin action, while men showed the strongest associations with peripheral insulin sensitivity and age in reward‐related brain regions. Conclusion: We could show a region‐specific relationship between brain insulin responsiveness, age and peripheral insulin sensitivity. Our findings underline the need to study brain insulin action in both men and women and further substantiate that brain insulin sensitivity is a possible link between systemic metabolism and neurocognitive functions.
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In previous placebo-controlled assessments, the placebo nasal spray did not impact hypothalamic blood flow.
“However, in our previous placebo-controlled assessments6,8,39 (see Supplementary Material 2 for more details), the placebo nasal spray did not impact hypothalamic blood flow.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [39]
The authors evaluated hypothalamic CBF response before and 30 min after placebo administration based on previous publications.
“we evaluated hypothalamic CBF response before and 30 min after placebo administration based on previous publications8,39.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [39]
No significant change in hypothalamic blood flow was observed in 110 healthy participants (P > 0.05).
“No significant change in hypothalamic blood flow was observed in 110 healthy participants (P > 0.05).”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [39]
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Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase
Hummel, J., Benkendorff, C., Fritsche, L., Prystupa, K., Vosseler, A., Gancheva, S., Trenkamp, S., Birkenfeld, A. L., Preissl, H., Roden, M., et al. (2023) · Nature Metabolism · doi:10.1038/s42255-023-00869-w · Cited by 48 · see citing works
Self-citation
- Authors
- Wagner, L., Veit, R., Kübler, C., Fritsche, A., Häring, H., Birkenfeld, A. L., Heni, M., Preissl, H., & Kullmann, S.
- Affiliations
- German Center for Diabetes Research (DE)
- University of Tübingen (DE)
- Universitätsklinikum Tübingen (DE)
- Helmholtz Munich (DE)
- Corresponding author
- Wagner, Lore
- Kullmann, Stephanie
- ORCID
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2023-05-04
- Volume
- 25
- Issue
- 8
- Pages
- 2171-2180
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- OpenAlex
- W4365443217
- Cited by
- 22
- References
- 74
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 7 · 2023: 1
- FWCI
- 3.28
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes Obesity and Metabolism (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- insulin sensitivity, aging, hippocampus, caudate nucleus, amygdala, insula, sex differences, cerebral blood flow, oral glucose tolerance test, brain reward system, neurocognitive function
- MeSH terms
- Adult, Aged, Brain, Female, Glucose Tolerance Test, Humans, Insulin, Insulin Resistance, Male, Middle Aged, Young Adult, Insulin, Regular, Human
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