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Synaptic Glutamate Release by Ventromedial Hypothalamic Neurons Is Part of the Neurocircuitry that Prevents Hypoglycemia
Open accessAbstract
The importance of neuropeptides in the hypothalamus has been experimentally established. Due to difficulties in assessing function in vivo, the roles of the fast-acting neurotransmitters glutamate and GABA are largely unknown. Synaptic vesicular transporters (VGLUTs for glutamate and VGAT for GABA) are required for vesicular uptake and, consequently, synaptic release of neurotransmitters. Ventromedial hypothalamic (VMH) neurons are predominantly glutamatergic and express VGLUT2. To evaluate the role of glutamate release from VMH neurons, we generated mice lacking VGLUT2 selectively in SF1 neurons (a major subset of VMH neurons). These mice have hypoglycemia during fasting secondary to impaired fasting-induced increases in the glucose-raising pancreatic hormone glucagon and impaired induction in liver of mRNAs encoding PGC-1alpha and the gluconeogenic enzymes PEPCK and G6Pase. Similarly, these mice have defective counterregulatory responses to insulin-induced hypoglycemia and 2-deoxyglucose (an antimetabolite). Thus, glutamate release from VMH neurons is an important component of the neurocircuitry that functions to prevent hypoglycemia.
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“and play a main role in the regulation of energy balance (Tong et al., 2007).”
From A Functional Link between AMPK and Orexin Mediates the Effect of BMP8B on Energy Balance (2016) · cites this paper as Tong et al., 2007
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Energy Metabolism in the Liver
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“As previously mentioned, SF1 neurons are glutamatergic (Figure 1 and (Tong et al., 2007)).”
Neuropeptide Transmission in Brain Circuits
van den Pol, A. N. (2012) · Neuron · doi:10.1016/j.neuron.2012.09.014 · Cited by 810
“…line of work has shown that knocking out glutamate neurotransmission from SF1 neurons of the hypothalamic ventromedial nucleus disturbs glucose regulation and causes mice to suffer from hypoglycemia during fasting, and to have defective responses to insulin-induced hypoglycemia (Tong et al, 2007).”
BackgroundSynaptic release of GABA by AgRP neurons is required for normal regulation of energy balance
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“3b ), accompanied by an increase in c-Fos immunoreactivity, a marker of neuronal activatio”
Background
Metadata
- Authors
- Tong, Q., Ye, C., McCrimmon, R. J., Dhillon, H., Choi, B., Kramer, M. D., Yu, J., Yang, Z., Christiansen, L. M., Lee, C. E., Choi, C. S., Zigman, J. M., Shulman, G. I., Sherwin, R. S., Elmquist, J. K., & Lowell, B. B.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Yale University (US)
- The University of Texas Southwestern Medical Center (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Lowell, Bradford B.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2007-05
- Volume
- 5
- Issue
- 5
- Pages
- 383-393
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC1934926
- OpenAlex
- W1995998852
- Cited by
- 413
- References
- 62
- Citations by year
- 2026: 10 · 2025: 20 · 2024: 32 · 2023: 23 · 2022: 23 · 2021: 30 · 2020: 22 · 2019: 10 · 2018: 25 · 2017: 27 · 2016: 16 · 2015: 19 · 2014: 20 · 2013: 26 · 2012: 27
- FWCI
- 7.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion)
- Funders
- American Diabetes Association Research Foundation
- Richard and Susan Smith Family Foundation
- Boston Area Diabetes Endocrinology Research Center
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK057521, P01DK56116, R01DK071051, P01DK056116, P30DK046200, R01DK040936, R01DK071320, U24DK059635, DK071320, R01DK069831, R01DK072409, R37DK020495)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- ventromedial hypothalamus, glutamate release, VGLUT2, glucagon, hypoglycemia, insulin-induced hypoglycemia, PGC-1α, gluconeogenesis, phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, 2-deoxyglucose, hypothalamic neurons, glucose homeostasis
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Animals, Electrophysiology, Glucagon, Glucose-6-Phosphatase, Hypoglycemia, Hypothalamus, Insulin, Liver, Mice, Transgenic, Neurons, Synapses, Transcription Factors, Trans-Activators, In Situ Hybridization, Glutamic Acid, Vesicular Glutamate Transport Protein 2, Mice
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