The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Regulation of Blood Glucose by Hypothalamic Pyruvate Metabolism
Abstract
The brain keenly depends on glucose for energy, and mammalians have redundant systems to control glucose production. An increase in circulating glucose inhibits glucose production in the liver, but this negative feedback is impaired in type 2 diabetes. Here we report that a primary increase in hypothalamic glucose levels lowers blood glucose through inhibition of glucose production in rats. The effect of glucose requires its conversion to lactate followed by stimulation of pyruvate metabolism, which leads to activation of adenosine triphosphate (ATP)–sensitive potassium channels. Thus, interventions designed to enhance the hypothalamic sensing of glucose may improve glucose homeostasis in diabetes.
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“The brain, on one hand, possesses its own glucose sensing machinery that protects itself from hypoglycemic injury by triggering a rapid secretion of counterregulatory hormones in response to low extracellular glucose levels [2].”
From A mathematical model of brain glucose homeostasis (2009) · cites this paper as [2]
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Cites
Pellerin, L., & Magistretti, P. J. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.22.10625 · Cited by 2,927
Impaired Mitochondrial Activity in the Insulin-Resistant Offspring of Patients with Type 2 Diabetes
Petersen, K. F., Dufour, S., Befroy, D., Garcia, R., & Shulman, G. I. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa031314 · Cited by 2,193
Mitochondrial dysfunction in the elderly: possible role in insulin resistance
Petersen, K. F., Befroy, D., Dufour, S., Dziura, J., Ariyan, C., Rothman, D. L., DiPietro, L., Cline, G. W., & Shulman, G. I. (2003) · Science · doi:10.1126/science.1082889 · Cited by 2,107
Mitochondrial dysfunction and type 2 diabetes
Lowell, B. B., & Shulman, G. I. (2005) · Science · doi:10.1126/science.1104343 · Cited by 2,070
Magistretti, P. J., Pellerin, L., Rothman, D. L., & Shulman, R. G. (1999) · Science · doi:10.1126/science.283.5401.496 · Cited by 1,170
Cryer, P. E., Davis, S. N., & Shamoon, H. (2003) · Diabetes Care · doi:10.2337/diacare.26.6.1902 · Cited by 1,160
Flier, J. S. (2004) · Cell · doi:10.1016/s0092-8674(03)01081-x · Cited by 1,122
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-citationDiabetes, Obesity, and the Brain
Schwartz, M. W., & Porte, D. (2005) · Science · doi:10.1126/science.1104344 · Cited by 841
Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis
Kasischke, K. A., Vishwasrao, H. D., Fisher, P. J., Zipfel, W. R., & Webb, W. W. (2004) · Science · doi:10.1126/science.1096485 · Cited by 742
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Ojha, A., & Watve, M. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.01.19.477014
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Obici, S., & Martins, P. J. F. (2016) · Springer eBooks · doi:10.1007/978-3-319-20797-1_6-1
Das, U. N. (2011) · Springer eBooks · doi:10.1007/978-94-007-0495-4_14
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de Souza, A. P., Pedroso, A. P., de Andrade, M. C. C., Telles, M. M., Boldarine, V. T., Oyama, L. M., Tashima, A. K., & Ribeiro, E. B. (2022) · Research Square · doi:10.21203/rs.3.rs-1348063/v1
de Souza, A. P., Pedroso, A. P., de Andrade, M. C. C., Telles, M. M., Boldarine, V. T., Oyama, L. M., Tashima, A. K., & Ribeiro, E. B. (2022) · Research Square · doi:10.21203/rs.3.rs-1348063/v2
Michels, G., & Hoppe, U. C. (2010) · Springer eBooks · doi:10.1007/978-3-642-04960-6_9
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(2005) · Science of Aging Knowledge Environment · doi:10.1126/sageke.2005.32.nw30
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Zakharova, I. O., Bayunova, L. V., Derkach, K. V., Ilyasov, I. O., Morina, I. Y., Shpakov, A. O., & Avrova, N. F. (2022) · Journal of Evolutionary Biochemistry and Physiology · doi:10.1134/s0022093022060072
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Ghosh, A., Barik, A., Kumar, R., Wall, J. D., Chowdhury, A., & Majumder, P. P. (2025) · Journal of Genetics · doi:10.1007/s12041-025-01498-w
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Wang, N., Gu, W., Liu, S., Wu, M., Luo, C., Chai, Z., & Zhang, F. (2025) · PeerJ Computer Science · doi:10.7717/peerj-cs.3223
Bermeo, K., Rosendo-Pineda, M. J., Arenas, T., Arenas, I., & Garcia, D. E. (2025) · Neuropeptides · doi:10.1016/j.npep.2025.102582
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Horváth, T. L. (2012) · Humana Press eBooks · doi:10.1007/978-1-61779-903-7_9
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Dischinger, U., & Michels, G. (2026) · Springer eBooks · doi:10.1007/978-3-662-71761-5_19
Détection des nutriments et contrôle central de la prise alimentaire
Delaere, F. (2009) · theses.fr (ABES) · doi:10.70675/2e9fa6a2z6f59z4d47zaabbz04010b09ce15
Hamel, L., Pereira, S. X. E. R. L., Yang, Z., Garrido, A. N., Agarwal, S. M., Lam, T. K. T., & Hahn, M. K. (2026) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-026-10034-9 · Cited by 1
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Pocai, A., & 杜复勇 (2026) · Trends Open · doi:10.1016/j.treopn.2026.09.001
Self-citationZhou, Z., Shi, X., 姜苏原, Wang, S., Shu, H., Sun, W., Wang, H., Cong, L., Mao, L., Fu, L., et al. (2026) · Cell Metabolism · doi:10.1016/j.cmet.2026.10.010
Metadata
- Authors
- Lam, T. K. T., Gutierrez-Juarez, R., Pocai, A., & Rossetti, L.
- Affiliations
- Albert Einstein College of Medicine (US)
- Departments of Medicine and Molecular Pharmacology, Diabetes Research Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
- Corresponding author
- Rossetti, Luciano
- Venue
- Science
- Published
- 2005-08-05
- Volume
- 309
- Issue
- 5736
- Pages
- 943-947
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1963957834
- Cited by
- 341
- References
- 32
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 11 · 2023: 8 · 2022: 16 · 2021: 13 · 2020: 7 · 2019: 15 · 2018: 11 · 2017: 9 · 2016: 22 · 2015: 25 · 2014: 11 · 2013: 26 · 2012: 18
- FWCI
- 23.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (P01AG021654, AG 21654, T32AG023475)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-48321, 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
- blood glucose regulation, hypothalamus, pyruvate metabolism, glucose detection, hepatic glucose production, type 2 diabetes, lactate, ATP-sensitive potassium channels, glucose homeostasis, negative feedback
- MeSH terms
- Animals, Astrocytes, Blood Glucose, Citric Acid Cycle, Glucose, Glucose-6-Phosphatase, Hypothalamus, Injections, Intraventricular, Liver, Male, Neurons, Pyruvates, Potassium Channels, Rats, Sprague-Dawley, Lactic Acid, Feedback, Physiological, Rats
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