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Impaired insulin action in the human brain: causes and metabolic consequences
Abstract
Over the past few years, evidence has accumulated that the human brain is an insulin-sensitive organ. Insulin regulates activity in a limited number of specific brain areas that are important for memory, reward, eating behaviour and the regulation of whole-body metabolism. Accordingly, insulin in the brain modulates cognition, food intake and body weight as well as whole-body glucose, energy and lipid metabolism. However, brain imaging studies have revealed that not everybody responds equally to insulin and that a substantial number of people are brain insulin resistant. In this Review, we provide an overview of the effects of insulin in the brain in humans and the relevance of the effects for physiology. We present emerging evidence for insulin resistance of the human brain. Factors associated with brain insulin resistance such as obesity and increasing age, as well as possible pathogenic factors such as visceral fat, saturated fatty acids, alterations at the blood-brain barrier and certain genetic polymorphisms, are reviewed. In particular, the metabolic consequences of brain insulin resistance are discussed and possible future approaches to overcome brain insulin resistance and thereby prevent or treat obesity and type 2 diabetes mellitus are outlined.
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“although other factors, such as genetic background19, elevated circulating free fatty acids20 and impaired insulin transport across the blood–brain barrier21,22, have also been implicated.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [19]
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Metadata
- Authors
- Heni, M., Kullmann, S., Preissl, H., Fritsche, A., & Häring, H.-U.
- Affiliations
- German Center for Diabetes Research (DE)
- Corresponding author
- Heni, Martin
- Venue
- Nature Reviews Endocrinology
- Published
- 2015-10-13
- Volume
- 11
- Issue
- 12
- Pages
- 701-711
- ISSN
- 1759-5029 (ISSN-L)
- 1759-5037
- OpenAlex
- W2199402593
- Cited by
- 245
- References
- 158
- Citations by year
- 2026: 15 · 2025: 7 · 2024: 10 · 2023: 22 · 2022: 28 · 2021: 24 · 2020: 25 · 2019: 32 · 2018: 23 · 2017: 28 · 2016: 29 · 2015: 1
- FWCI
- 2.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Site cant be reached (submittedVersion)
- Funders
- Bundesministerium für Bildung und Forschung
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- brain insulin resistance, obesity, type 2 diabetes, visceral fat, saturated fatty acids, blood-brain barrier, genetic polymorphism, food intake regulation, energy metabolism, whole-body glucose metabolism, lipid metabolism, cognitive function, eating behaviour
- MeSH terms
- Body Weight, Brain Chemistry, Cognition, Diabetes Mellitus, Type 2, Feeding Behavior, Humans, Insulin, Insulin Resistance
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