The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
A brain-liver circuit regulates glucose homeostasis
Open accessAbstract
Increased glucose production (GP) is the major determinant of fasting hyperglycemia in diabetes mellitus. Previous studies suggested that lipid metabolism within specific hypothalamic nuclei is a biochemical sensor for nutrient availability that exerts negative feedback on GP. Here we show that central inhibition of fat oxidation leads to selective activation of brainstem neurons within the nucleus of the solitary tract and the dorsal motor nucleus of the vagus and markedly decreases liver gluconeogenesis, expression of gluconeogenic enzymes, and GP. These effects require central activation of ATP-dependent potassium channels (K(ATP)) and descending fibers within the hepatic branch of the vagus nerve. Thus, hypothalamic lipid sensing potently modulates glucose metabolism via neural circuitry that requires the activation of K(ATP) and selective brainstem neurons and intact vagal input to the liver. This crosstalk between brain and liver couples central nutrient sensing to peripheral nutrient production and its disruption may lead to hyperglycemia.
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“Consistent with this hypothesis, both local administration of insulin and inhibition of fat oxidation in the ARC increase hepatic insulin sensitivity via a mechanism that requires intact hepatic vagal innervation, and also activates hindbrain neurons within both the NTS and DMX (147).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [147]
In the citing paper
“Although accumulating evidence suggests that leptin (10 -13), insulin (14,15), and nutrient-related signals (16 -18) in the CNS improve hepatic insulin sensitivity”
From Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia (2011) · cites this paper as [18]
Citations
Cites
Central nervous system control of food intake
Schwartz, M. W., Woods, S. C., Porte, D., Seeley, R. J., & Baskin, D. G. (2000) · Nature · doi:10.1038/35007534 · Cited by 6,451
Global and societal implications of the diabetes epidemic
Zimmet, P., Alberti, K. G. M. M., & Shaw, J. (2001) · Nature · doi:10.1038/414782a · Cited by 5,883
Kopelman, P. G. (2000) · Nature · doi:10.1038/35007508 · Cited by 4,795
Tracey, K. J. (2002) · Nature · doi:10.1038/nature01321 · Cited by 3,728
Obesity and insulin resistance
Kahn, B. B., & Flier, J. S. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10842 · Cited by 3,345
Flier, J. S. (2004) · Cell · doi:10.1016/s0092-8674(03)01081-x · Cited by 1,122
New drug targets for type 2 diabetes and the metabolic syndrome
Moller, D. E. (2001) · Nature · doi:10.1038/414821a · Cited by 1,012
Reduced Food Intake and Body Weight in Mice Treated with Fatty Acid Synthase Inhibitors
Loftus, T. M., Jaworsky, D. E., Frehywot, G. L., Townsend, C. A., Ronnett, G. V., Lane, M. D., & Kuhajda, F. P. (2000) · Science · doi:10.1126/science.288.5475.2379 · Cited by 1,004
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
Self-citationA possible role for malonyl-CoA in the regulation of hepatic fatty acid oxidation and ketogenesis.
McGarry, J. D., Mannaerts, G. P., & Foster, D. W. (1977) · Journal of Clinical Investigation · doi:10.1172/jci108764 · Cited by 736
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Self-citationThe vagus nerve and the inflammatory reflex – linking immunity and metabolism
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Metadata
- Authors
- Pocai, A., Obici, S., Schwartz, G. J., & Rossetti, L.
- Affiliations
- Albert Einstein College of Medicine (US)
- Corresponding author
- Rossetti, Luciano
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2005-01
- Volume
- 1
- Issue
- 1
- Pages
- 53-61
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2054716401
- Cited by
- 392
- References
- 43
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 20 · 2023: 9 · 2022: 15 · 2021: 14 · 2020: 19 · 2019: 16 · 2018: 10 · 2017: 22 · 2016: 19 · 2015: 17 · 2014: 15 · 2013: 21 · 2012: 26
- FWCI
- 27.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-48321, DK-47208, R01DK047208, DK20541, DK-45024)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- glucose homeostasis, fasting hyperglycemia, liver gluconeogenesis, glucose production, nucleus tractus solitarius, dorsal motor nucleus of the vagus, brainstem neurons, ATP-sensitive potassium channels, fat oxidation, diabetes mellitus
- MeSH terms
- Adenosine Triphosphate, Animals, Brain, Central Nervous System, Glucose, Homeostasis, Hyperglycemia, Kinetics, Liver, Male, Models, Biological, Neurons, Oxygen, Pancreas, Phosphoric Monoester Hydrolases, Potassium, Vagus Nerve, Potassium Channels, Glucose Clamp Technique, Proto-Oncogene Proteins c-fos, Rats, Sprague-Dawley, Reverse Transcriptase Polymerase Chain Reaction, Lipid Metabolism, Rats
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