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 possesses its own glucose sensing machinery that protects itself from hypoglycemic injury by triggering rapid secretion of counterregulatory hormones in response to low extracellular glucose levels.
“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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- 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 › Surgery › 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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