Profiling of Glucose-Sensing Neurons Reveals that GHRH Neurons Are Activated by Hypoglycemia
Open accessAbstract
Comprehensive transcriptional profiling of glucose-sensing neurons is challenging because of low expression levels of glucokinase (Gck) and other key proteins that transduce a glucose signal. To overcome this, we generated and validated transgenic mice with a neuronal/endocrine-specific Gck promoter driving cre expression and mated them to mice with cre-dependent expression of an EGFP-tagged ribosomal protein construct (EEF1A1-LSL.EGFPL10) that can be used to map and profile cells. We found significant Gck expression in hypothalamic and limbic regions in cells that are activated following administration of glucose or 2-deoxyglucose. Transcriptional profiling from Gck-cre/EEF1A1-LSL.EGFPL10 mice enriched known and previously unknown glucose-sensing populations including neurons expressing growth hormone releasing hormone (GHRH). Electrophysiological recordings show that hypoglycemia activates GHRH neurons, suggesting a mechanistic link between hypoglycemia and growth hormone release. These studies provide a means for mapping glucose-sensitive neurons and for generating transcriptional profiles from other cell types expressing cre in a cell-specific manner.
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The TRAP approach relies on the genetic labelling of the ribosomal protein L10a with the enhanced green fluorescent protein (eGFP) using Eef1a1LSL.eGFPL10a/+ mice.
“The TRAP approach91,92 relies on the genetic labelling of the ribosomal protein L10a with the enhanced green fluorescent protein (eGFP) using Eef1a1LSL.eGFPL10a/+ mice60.”
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- Authors
- Stanley, S., Domingos, A. I., Kelly, L., Garfield, A., Damanpour, S., Heisler, L., & Friedman, J.
- Affiliations
- Rockefeller University (US)
- University of Edinburgh (GB)
- University of Aberdeen (GB)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Friedman, Jeffrey
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2013-10
- Volume
- 18
- Issue
- 4
- Pages
- 596-607
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W1973368725
- Cited by
- 110
- References
- 2
- Citations by year
- 2026: 3 · 2025: 12 · 2024: 5 · 2023: 5 · 2022: 11 · 2021: 6 · 2020: 6 · 2019: 10 · 2018: 11 · 2017: 10 · 2016: 10 · 2015: 13 · 2014: 7 · 2013: 1
- FWCI
- 10.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- JPB Foundation
- Wellcome Trust (098012, WT098012)
- Medical Research Council
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- glucose-sensing neurons, glucokinase, hypoglycemia, growth hormone secretion, hypothalamus, limbic system, gene expression profiling, 2-deoxyglucose, transgenic mice
- MeSH terms
- Animals, Deoxyglucose, Glucokinase, Glucose, Hypoglycemia, Hypothalamus, Male, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Ribosomal Proteins, Growth Hormone-Releasing Hormone, Gene Expression Profiling, Green Fluorescent Proteins, Mice
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