Cited by 413Regulation of Appetite and ObesityPancreatic function and diabetesNeuroscience and Neuropharmacology Research

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Synaptic Glutamate Release by Ventromedial Hypothalamic Neurons Is Part of the Neurocircuitry that Prevents Hypoglycemia

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Tong, Qingchun, Ye, ChianPing, McCrimmon, Rory J., Dhillon, Harveen, Choi, Brian, Kramer, Melissa D., Yu, Jia, Yang, Zongfang, Christiansen, Lauryn M., Lee, Charlotte E., Choi, Cheol Soo, Zigman, Jeffrey M., Shulman, Gerald I., Sherwin, Robert S., Elmquist, Joel K., Lowell, Bradford B.·2007·Cell Metabolism

DOI 10.1016/j.cmet.2007.04.001PMC PMC1934926

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Abstract

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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“…of identifying the specific neurotransmitter responses that are impaired in HAAF, there is evidence for altered CNS GABAergic (gamma-aminobutyric acid) 35,36 and glutaminergic 37 signaling; however, the role for other neurotransmitters in the development of HAAF has not been fully characterized.”

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: Tong, Qingchun
McCrimmon, Rory J.
Yu, Jia
Lee, Charlotte E.
Choi, Cheol Soo
Zigman, Jeffrey M.
Shulman, Gerald I.
Elmquist, Joel K.
Lowell, Bradford B.
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2007-05
Volume: 5
Issue: 5
Pages: 383-393
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2007.04.001
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2305 d)
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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Synaptic Glutamate Release by Ventromedial Hypothalamic Neurons Is Part of the Neurocircuitry that Prevents Hypoglycemia

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