Brain insulin signalling in metabolic homeostasis and disease
Abstract
Insulin signalling in the central nervous system regulates energy homeostasis by controlling metabolism in several organs and by coordinating organ crosstalk. Studies performed in rodents, non-human primates and humans over more than five decades using intracerebroventricular, direct hypothalamic or intranasal application of insulin provide evidence that brain insulin action might reduce food intake and, more importantly, regulates energy homeostasis by orchestrating nutrient partitioning. This Review discusses the metabolic pathways that are under the control of brain insulin action and explains how brain insulin resistance contributes to metabolic disease in obesity, the metabolic syndrome and type 2 diabetes mellitus.
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The brain is an insulin-sensitive organ.
“Over the last decade, the brain was characterized as an insulin-sensitive organ1.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [1]
Insulin action in the human brain modulates eating behaviour, whole-body metabolism and body fat distribution.
“Insulin action in the human brain modulates eating behaviour, whole-body metabolism and body fat distribution1,2.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [1]
Insulin acts in specialized neurons and glia cells.
“acts in specialized neurons and glia cells1”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [1]
The most prominent phenotype linked to human brain insulin resistance is obesity.
“The most prominent phenotype linked to human brain insulin resistance is obesity1”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [1]
Insulin receptors are highly expressed in the brain, including the hypothalamus, olfactory bulb, hippocampus, striatum, cerebral cortex, and cerebellum.
“Insulin receptors are highly expressed in the brain, not only in the hypothalamus, olfactory bulb, hippocampus, and striatum, but also in cerebral cortex, and cerebellum.175”
From The blood–brain barrier: Structure, regulation and drug delivery (2023) · cites this paper as [175]
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- Authors
- Scherer, T., Sakamoto, K., & Buettner, C.
- Affiliations
- Medical University of Vienna (AT)
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Scherer, Thomas
- Buettner, Christoph
- Venue
- Nature Reviews Endocrinology
- Published
- 2021-06-09
- Volume
- 17
- Issue
- 8
- Pages
- 468-483
- ISSN
- 1759-5029 (ISSN-L)
- 1759-5037
- OpenAlex
- W3167467420
- Cited by
- 205
- References
- 255
- Citations by year
- 2026: 38 · 2025: 36 · 2024: 61 · 2023: 35 · 2022: 30 · 2021: 5
- FWCI
- 4.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Reviews Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- 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 › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- insulin resistance, energy homeostasis, nutrient partitioning, food intake regulation, obesity, metabolic syndrome, type 2 diabetes, hypothalamus, intranasal insulin, organ crosstalk, metabolic disease treatment
- MeSH terms
- Animals, Brain, Diabetes Mellitus, Type 2, Energy Metabolism, Homeostasis, Humans, Insulin, Insulin Resistance, Metabolic Diseases, Signal Transduction, Metabolic Syndrome
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