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

Research output: Contribution to journalArticlepeer-review

64 Citations (Scopus)

Abstract

SUMMARY Comprehensive transcriptional profiling of glucosesensing 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 EGFPtagged 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. ?? 2013 Elsevier Inc.
Original languageEnglish
Pages (from-to)596-607
Number of pages12
JournalCell Metabolism
Volume18
Issue number4
DOIs
Publication statusPublished - 1 Oct 2013

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