Central Insulin Administration Improves Whole-Body Insulin Sensitivity via Hypothalamus and Parasympathetic Outputs in Men
Abstract
Animal studies suggest that insulin action in the brain is involved in the regulation of peripheral insulin sensitivity. Whether this holds true in humans is unknown. Using intranasal application of insulin to the human brain, we studied the impacts of brain insulin action on whole-body insulin sensitivity and the mechanisms involved in this process. Insulin sensitivity was assessed by hyperinsulinemic-euglycemic glucose clamp before and after intranasal application of insulin and placebo in randomized order in lean and obese men. After insulin spray application in lean subjects, a higher glucose infusion rate was necessary to maintain euglycemia compared with placebo. Accordingly, clamp-derived insulin sensitivity index improved after insulin spray. In obese subjects, this insulin-sensitizing effect could not be detected. Change in the high-frequency band of heart rate variability, an estimate of parasympathetic output, correlated positively with change in whole-body insulin sensitivity after intranasal insulin. Improvement in whole-body insulin sensitivity correlated with the change in hypothalamic activity as assessed by functional magnetic resonance imaging. Intranasal insulin improves peripheral insulin sensitivity in lean but not in obese men. Furthermore, brain-derived peripheral insulin sensitization is associated with hypothalamic activity and parasympathetic outputs. Thus, the findings provide novel insights into the regulation of insulin sensitivity and the pathogenesis of insulin resistance in humans.
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Studies on brain insulin action increasing whole-body insulin sensitivity were mainly performed in lean men.
“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 [4]
Brain insulin action increases whole-body insulin sensitivity.
“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 [4]
The current study corroborates that insulin action in the human brain modulates peripheral insulin sensitivity.
“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 [4]
Insulin action in the hypothalamus has a crucial role in the modulation of whole-body glucose metabolism.
“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 [4]
In lean women, the effects on peripheral insulin sensitivity in the follicular phase were comparable in timing and magnitude to previous findings obtained in lean men.
“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 [4]
Insulin action in the human brain modulates peripheral insulin sensitivity.
“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 [4]
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- Authors
- Heni, M., Wagner, R., Kullmann, S., Veit, R., Mat Husin, H., Linder, K., Benkendorff, C., Peter, A., Stefan, N., Häring, H.-U., Preissl, H., & Fritsche, A.
- Affiliations
- German Center for Diabetes Research (DE)
- Institute of Medical Psychology and Behavioral Neurobiology/fMEG Center, Eberhard Karls University Tübingen, Tübingen, Germany
- University of Tübingen (DE)
- Corresponding author
- Wagner, Robert
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2014-11-13
- Volume
- 63
- Issue
- 12
- Pages
- 4083-4088
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2128507030
- Cited by
- 167
- References
- 27
- Citations by year
- 2026: 11 · 2025: 10 · 2024: 8 · 2023: 7 · 2022: 6 · 2021: 16 · 2020: 15 · 2019: 17 · 2018: 14 · 2017: 23 · 2016: 14 · 2015: 21 · 2014: 5
- FWCI
- 10.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Site cant be reached (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, Cardiovascular Risks, and Lipoproteins
- Keywords
- intranasal insulin, whole-body insulin sensitivity, hypothalamic activity, heart rate variability, obesity, insulin resistance, lean men
- MeSH terms
- Administration, Intranasal, Adult, Blood Glucose, Cerebrovascular Circulation, Heart Rate, Humans, Hypoglycemic Agents, Hypothalamus, Infusions, Intravenous, Insulin, Insulin Resistance, Magnetic Resonance Imaging, Male, Obesity, Parasympathetic Nervous System, Glucose Clamp Technique, Young Adult, Functional Neuroimaging
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