The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Hypothalamic and Striatal Insulin Action Suppresses Endogenous Glucose Production and May Stimulate Glucose Uptake During Hyperinsulinemia in Lean but Not in Overweight Men
Abstract
Intranasal spray application facilitates insulin delivery to the human brain. Although brain insulin modulates peripheral metabolism, the mechanisms involved remain elusive. Twenty-one men underwent two hyperinsulinemic-euglycemic clamps with d-[6,6-2H2]glucose infusion to measure endogenous glucose production and glucose disappearance. On two separate days, participants received intranasal insulin or placebo. Insulin spillover into circulation after intranasal insulin application was mimicked by an intravenous insulin bolus on placebo day. On a different day, brain insulin sensitivity was assessed by functional MRI. Glucose infusion rates (GIRs) had to be increased more after nasal insulin than after placebo to maintain euglycemia in lean but not in overweight people. The increase in GIRs was associated with regional brain insulin action in hypothalamus and striatum. Suppression of endogenous glucose production by circulating insulin was more pronounced after administration of nasal insulin than after placebo. Furthermore, glucose uptake into tissue tended to be higher after nasal insulin application. No such effects were detected in overweight participants. By increasing insulin-mediated suppression of endogenous glucose production and stimulating peripheral glucose uptake, brain insulin may improve glucose metabolism during systemic hyperinsulinemia. Obese people appear to lack these mechanisms. Therefore, brain insulin resistance in obesity may have unfavorable consequences for whole-body glucose homeostasis.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Previous findings from healthy men indicate that brain insulin most likely modulates both3.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [3]
In the citing paper
“these studies were mainly performed in lean men3,4”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [3]
In the citing paper
“brain insulin action increases whole-body insulin sensitivity”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [3]
In the citing paper
“and stimulates glucose uptake into peripheral tissues3”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [3]
In the citing paper
“Studies performed in healthy men found that insulin action in the brain suppresses endogenous glucose production3,11”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [3]
In the citing paper
“The current study corroborates that insulin action in the human brain modulates peripheral insulin sensitivity3,4,11”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [3]
In the citing paper
“Here, the effects on peripheral insulin sensitivity were comparable in timing and magnitude to previous findings obtained in lean men3,4.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [3]
In the citing paper
“The current study corroborates that insulin action in the human brain modulates peripheral insulin sensitivity3,4,11”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [3]
In the citing paper
“On the basis of our previous findings3,8, we assessed the insulin-induced response of hypothalamic cerebral blood flow (CBF) as a readout for hypothalamic insulin action.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [3]
In the citing paper
“In line with experimental evidence from animals30, previous correlational findings from humans indicate a crucial role of insulin action in the hypothalamus for the modulation of whole-body glucose metabolism3,4.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [3]
In the citing paper
“CBF was extracted from the hypothalamus as our region of interest, based on recent findings3,8.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [3]
In the citing paper
“the fMRI measurements indicated an involvement of the hypothalamus and striatum in these glucoregulatory effects of IN insulin, which, notably, were not found in obese individuals”
From Intranasal insulin (2021) · cites this paper as [80]
Citations
Cites
INFLUENCES OF GLUCOSE LOADING AND OF INJECTED INSULIN ON HEPATIC GLUCOSE OUTPUT*
Steele, R. D. (1959) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1959.tb44923.x · Cited by 1,680
Somatostatin and Its Receptor Family
Patel, Y. (1999) · Frontiers in Neuroendocrinology · doi:10.1006/frne.1999.0183 · Cited by 1,670
Sniffing neuropeptides: A transnasal approach to the human brain
Born, J., Lange, T., Kern, W., McGregor, G. P., Bickel, U., & Fehm, H. L. (2002) · Nature Neuroscience · doi:10.1038/nn0602-849 · Cited by 1,356
Hypothalamic insulin signaling is required for inhibition of glucose production
Obici, S., Zhang, B. B., Karkanias, G., & Rossetti, L. (2002) · Nature Medicine · doi:10.1038/nm1202-798 · Cited by 904
Decreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats
Obici, S., Feng, Z., Karkanias, G., Baskin, D. G., & Rossetti, L. (2002) · Nature Neuroscience · doi:10.1038/nn0602-861 · Cited by 719
Hypothalamic KATP channels control hepatic glucose production
Pocai, A., Lam, T. K. T., Gutierrez-Juarez, R., Obici, S., Schwartz, G. J., Bryan, J., Aguilar-Bryan, L., & Rossetti, L. (2005) · Nature · doi:10.1038/nature03439 · Cited by 645
Insulin Action in Brain Regulates Systemic Metabolism and Brain Function
Kleinridders, A., Ferris, H. A., Cai, W., & Kahn, C. R. (2014) · Diabetes · doi:10.2337/db14-0568 · Cited by 625
Decreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats
Obici, S., Feng, Z., Karkanias, G. B., et al. (2002) · Nature Neuroscience · doi:10.1038/nn861 · Cited by 572
Empirical optimization of ASL data analysis using an ASL data processing toolbox: ASLtbx
Wang, Z., Aguirre, G. K., Rao, H., Wang, J., Fernández‐Seara, M. A., Childress, A. R., & Detre, J. A. (2007) · Magnetic Resonance Imaging · doi:10.1016/j.mri.2007.07.003 · Cited by 479
A brain-liver circuit regulates glucose homeostasis
Pocai, A., Obici, S., Schwartz, G. J., & Rossetti, L. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2004.11.001 · Cited by 392
Flagged first, then by citations
Cited by
Sorted by citations
Mechanisms of Insulin Action and Insulin Resistance
Petersen, M. C., & Shulman, G. I. (2018) · Physiological Reviews · doi:10.1152/physrev.00063.2017 · Cited by 3,028
Central nervous pathways of insulin action in the control of metabolism and food intake
Kullmann, S., Kleinridders, A., Small, D. M., Fritsche, A., Häring, H.-U., Preissl, H., & Heni, M. (2020) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(20)30113-3 · Cited by 233
Self-citationBrain insulin signalling in metabolic homeostasis and disease
Scherer, T., Sakamoto, K., & Buettner, C. (2021) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00498-x · Cited by 205
Daily, J. W., Kang, S., & Park, S. (2020) · BioFactors · doi:10.1002/biof.1703 · Cited by 147
Insulin action in the brain regulates both central and peripheral functions
Agrawal, R., Reno, C. M., Sharma, S., CHRISTENSEN, C. G., Huang, Y., & Fisher, S. J. (2021) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00642.2020 · Cited by 153
Metadata
- Authors
- Heni, M., Wagner, R., Kullmann, S., Gancheva, S., Roden, M., Peter, A., Stefan, N., Preissl, H., Häring, H.-U., & Fritsche, A.
- Affiliations
- German Center for Diabetes Research (DE)
- Deutsches Diabetes-Zentrum e.V. (DE)
- Helmholtz Munich (DE)
- Corresponding author
- Heni, Martin
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2017-02-07
- Volume
- 66
- Issue
- 7
- Pages
- 1797-1806
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2586809204
- Cited by
- 115
- References
- 43
- Citations by year
- 2026: 10 · 2025: 7 · 2024: 13 · 2023: 10 · 2022: 11 · 2021: 12 · 2020: 15 · 2019: 14 · 2018: 19 · 2017: 4
- FWCI
- 14.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Site cant be reached (submittedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Funders
- Federal Ministry of Education and Research (01GI0925)
- Helmholtz-Gemeinschaft (Helmholtz Alliance ICEMED-Imaging and Curing Environmental Metabolic Diseases)
- European Foundation for the Study of Diabetes (Rising Star award supported by Novo Nordisk)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- hypothalamus, striatum, endogenous glucose production, glucose uptake, hyperinsulinemia, intranasal insulin, brain insulin resistance, obesity, glucose metabolism, glucose homeostasis
- MeSH terms
- Adult, Blood Glucose, Brain, Deuterium, Gluconeogenesis, Glucose, Humans, Hypoglycemic Agents, Hypothalamus, Insulin, Magnetic Resonance Imaging, Male, Thinness, Glucose Clamp Technique, Case-Control Studies, Neostriatum, Overweight, Young Adult, Functional Neuroimaging
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 ›
Are you an author, or do you see a problem with this page? Request a review
