The Catabolic Action of Insulin in the Brain Is Mediated by Melanocortins
Open accessAbstract
Like leptin, the pancreatic hormone insulin is an important adiposity signal to the brain. We report that the hypothalamic melanocortin system is an important target of the actions of insulin to regulate food intake and body weight. Hypothalamic neurons expressing insulin receptors were found to coexpress the melanocortin precursor molecule pro-opiomelanocortin (POMC), and administration of insulin into the third cerebral ventricle of fasted rats increased expression of POMC mRNA. Finally, a subthreshold dose of the melanocortin antagonist SHU-9119 prevented the reduction in food intake caused by third-ventricular insulin administration. These data suggest that the hypothalamic melanocortin system mediates the anorexic effects of central insulin, as well as of leptin.
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Insulin released in response to a meal enters the brain via the blood-brain barrier to decrease food intake by stimulating hypothalamic pro-opiomelanocortin neurons and initiating PI3K signaling in these neurons.
“Conversely, insulin released in response to a meal enters the brain via the blood–brain–barrier138 to decrease food intake139, 140 by stimulating hypothalamic pro-opiomelanocortin neurons141 and initiating the PI3K signaling pathway142 in these pro-opiomelanocortin neurons.143”
From Pancreatic regulation of glucose homeostasis. (2016) · cites this paper as [141]
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References 33 · Cited by 417
- Authors
- Benoit, S. C., Air, E. L., Coolen, L. M., Strauss, R., Jackman, A., Clegg, D. J., Seeley, R. J., & Woods, S. C.
- Affiliations
- University of Cincinnati (US)
- Procter & Gamble (United States) (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2002-10-15
- Volume
- 22
- Issue
- 20
- Pages
- 9048-9052
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6757684
- OpenAlex
- W1893713587
- Cited by
- 417
- References
- 33
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 8 · 2023: 8 · 2022: 6 · 2021: 21 · 2020: 8 · 2019: 12 · 2018: 16 · 2017: 20 · 2016: 20 · 2015: 14 · 2014: 19 · 2013: 22 · 2012: 30
- FWCI
- 5.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- insulin, melanocortin system, proopiomelanocortin, hypothalamus, food intake regulation, body weight regulation, insulin receptor, leptin, anorectic effect, adiposity signals
- MeSH terms
- Animals, Body Weight, Brain, Eating, Hypothalamus, Immunohistochemistry, Injections, Intraventricular, Insulin, Male, Melanocyte-Stimulating Hormones, Neurons, Pro-Opiomelanocortin, Receptor, Insulin, RNA, Messenger, Receptors, Corticotropin, Rats, Long-Evans, Rats
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