Profiling of Glucose-Sensing Neurons Reveals that GHRH Neurons Are Activated by Hypoglycemia

Sarah Stanley, Ana I. Domingos, Leah Kelly, Alastair Garfield, Shadi Damanpour, Lora Heisler, Jeffrey Friedman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)596-607
Number of pages12
JournalCell Metabolism
Volume18
Issue number4
DOIs
Publication statusPublished - 1 Oct 2013

Keywords

  • GROWTH-HORMONE-SECRETION
  • GLUCOKINASE GENE-EXPRESSION
  • CNS CELL-TYPES
  • OREXIN NEURONS
  • ARCUATE NUCLEUS
  • HYPOTHALAMIC NEURONS
  • RAT HYPOTHALAMUS
  • TRANSGENIC MICE
  • NERVOUS-SYSTEM
  • NEUROPEPTIDE-Y

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