Cited by 341Pancreatic function and diabetesRegulation of Appetite and ObesityMetabolism, Diabetes, and Cancer

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Regulation of Blood Glucose by Hypothalamic Pyruvate Metabolism

Lam, Tony K. T., Gutierrez-Juarez, Roger, Pocai, Alessandro, Rossetti, Luciano·2005·Science

DOI 10.1126/science.1112085

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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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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
ORCID: Lam, Tony K. T.
Pocai, Alessandro
Rossetti, Luciano
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2005-08-05
Volume: 309
Issue: 5736
Pages: 943-947
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1112085
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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Regulation of Blood Glucose by Hypothalamic Pyruvate Metabolism

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