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Hypoglycemia-Activated GLUT2 Neurons of the Nucleus Tractus Solitarius Stimulate Vagal Activity and Glucagon Secretion
Open accessAbstract
Glucose-sensing neurons in the brainstem participate in the regulation of energy homeostasis but have been poorly characterized because of the lack of specific markers to identify them. Here we show that GLUT2-expressing neurons of the nucleus of the tractus solitarius form a distinct population of hypoglycemia-activated neurons. Their response to low glucose is mediated by reduced intracellular glucose metabolism, increased AMP-activated protein kinase activity, and closure of leak K(+) channels. These are GABAergic neurons that send projections to the vagal motor nucleus. Light-induced stimulation of channelrhodospin-expressing GLUT2 neurons in vivo led to increased parasympathetic nerve firing and glucagon secretion. Thus GLUT2 neurons of the nucleus tractus solitarius link hypoglycemia detection to counterregulatory response. These results may help identify the cause of hypoglycemia-associated autonomic failure, a major threat in the insulin treatment of diabetes.
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“Hypoglycemia is directly sensed by GLUT2‐positive hypothalamic neurons that promote glucagon secretion via an increase in parasympathetic input 66.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [66]
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Metadata
- Authors
- Lamy, C. M., Sanno, H., Labouèbe, G., Picard, A., Magnan, C., Chatton, J.-Y., & Thorens, B.
- Affiliations
- University of Fribourg (CH)
- University of Lausanne (CH)
- Corresponding author
- Chatton, Jean-Yves
- Thorens, Bernard
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2014-03
- Volume
- 19
- Issue
- 3
- Pages
- 527-538
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2026372454
- Cited by
- 130
- References
- 35
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 8 · 2023: 14 · 2022: 15 · 2021: 19 · 2020: 11 · 2019: 10 · 2018: 9 · 2017: 5 · 2016: 13 · 2015: 10 · 2014: 8
- FWCI
- 11.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- SERVAL (Université de Lausanne) (acceptedVersion, other-oa)
- reroDoc Digital Library (submittedVersion)
- IRIS (submittedVersion)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (135720, 113525, 31003A, 3100A0)
- Université de Lausanne
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- nucleus tractus solitarius, hypoglycemia, glucose detection, AMPK, GABAergic neurons, parasympathetic nerve activity, glucagon secretion, counterregulatory response, hypoglycemia-associated autonomic failure, diabetes mellitus, energy homeostasis
- MeSH terms
- Channelrhodopsins, Animals, Deoxyglucose, Glucagon, Glucosamine, Glucose, Hypoglycemia, Membrane Potentials, Mice, Transgenic, Potassium Channels, Solitary Nucleus, Patch-Clamp Techniques, Glucose Transporter Type 2, Mice, AMP-Activated Protein Kinases, GABAergic Neurons, In Vitro Techniques
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