The cerebrocortical response to hyperinsulinemia is reduced in overweight humans: A magnetoencephalographic study
Open accessAbstract
Animal studies have shown that the brain is an insulin-responsive organ and that central nervous insulin resistance induces obesity and disturbances in glucose metabolism. In humans, insulin effects in the brain are poorly characterized. We used a magnetoencephalography approach during a two-step hyperinsulinemic euglycemic clamp to ( i ) assess cerebrocortical insulin effects in humans, ( ii ) compare these effects between 10 lean and 15 obese subjects, and ( iii ) test whether the insulin receptor substrate (IRS)-1 Gly972Arg polymorphism in the insulin-signaling cascade modifies these effects. Both spontaneous and stimulated (mismatch negativity) cortical activity were assessed. In lean humans, stimulated cortical activity ( P = 0.046) and the beta and theta band of spontaneous cortical activity ( P = 0.01 and 0.04) increased with insulin infusion relative to saline. In obese humans, these effects were suppressed. Moreover, the insulin effect on spontaneous cortical activity correlated negatively with body mass index and percent body fat (all r < −0.4; all P < 0.05) and positively with insulin sensitivity of glucose disposal (theta band, r = 0.48, P = 0.017). Furthermore, insulin increased spontaneous cortical activity (beta band) in carriers of wild-type IRS-1, whereas, in carriers of the 972Arg allele, this insulin effect was absent ( P = 0.01). We conclude that, in lean humans, insulin modulates cerebrocortical activity, and that these effects are diminished in obese individuals. Moreover, cerebrocortical insulin resistance is found in individuals with the Gly972Arg polymorphism in IRS-1, which is considered a type 2 diabetes risk gene.
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A substantial number of individuals have a reduced or even absent response to insulin in the brain.
“Initial studies on this topic have already revealed that a substantial number of individuals have a reduced or even absent response to insulin in the brain16”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [16]
The Abstract reports suppressed cerebrocortical responses to insulin in 15 obese subjects, and the Discussion says the effect in the obese group was much smaller or absent (page not available in our copy). This supports reduced or absent brain responses in the studied group, but the study does not establish that a substantial number of individuals in the wider population have such responses. (LLM, conf=0.84)
Experimental — accuracy not yet measuredOverweight compared with normal-weight subjects display decreased MEG-assessed cortical activity during hyperinsulinaemic-euglycaemic clamps.
“overweight in comparison with normal-weight subjects display decreased MEG-assessed cortical activity during hyperinsulineamic-euglycaemic clamps”
From Intranasal insulin (2021) · cites this paper as [86]
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- Authors
- Tschritter, O., Preissl, H., Hennige, A. M., Stumvoll, M., Porubska, K., Frost, R., Marx, H., Klösel, B., Lutzenberger, W., Birbaumer, N., Häring, H.-U., & Fritsche, A.
- Affiliations
- *Medizinische Klinik der Universität and
- University of Arkansas for Medical Sciences (US)
- Institute of Medical Psychology and Behavioural Neurobiology, University of Tübingen, 72076 Tübingen, Germany;
- University of Tübingen (DE)
- National Institutes of Health (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2006-08-08
- Volume
- 103
- Issue
- 32
- Pages
- 12103-12108
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1567704
- OpenAlex
- W2043314401
- Cited by
- 223
- References
- 44
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 9 · 2023: 7 · 2022: 8 · 2021: 12 · 2020: 8 · 2019: 13 · 2018: 16 · 2017: 13 · 2016: 11 · 2015: 18 · 2014: 10 · 2013: 15 · 2012: 14
- FWCI
- 3.65
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (KFO 114)
- 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, Cardiovascular Risks, and Lipoproteins
- Keywords
- hyperinsulinemia, brain insulin resistance, obesity, overweight, IRS-1, mismatch negativity, spontaneous cortical activity, beta band, theta band, type 2 diabetes risk, body mass index
- MeSH terms
- Adult, Cerebral Cortex, Diabetes Mellitus, Type 2, Female, Glucose, Humans, Hyperinsulinism, Insulin, Male, Obesity, Polymorphism, Genetic, Magnetoencephalography, Case-Control Studies, Overweight
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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