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 journalArticle

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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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Glucokinase
Hypoglycemia
Neurons
Glucose
Growth Hormone-Releasing Hormone
Ribosomal Proteins
Deoxyglucose
Transgenic Mice
Growth Hormone
Population
Proteins

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Stanley, S., Domingos, A. I., Kelly, L., Garfield, A., Damanpour, S., Heisler, L., & Friedman, J. (2013). Profiling of glucose-sensing neurons reveals that ghrh neurons are activated by hypoglycemia. Cell Metabolism, 18(4), 596-607. https://doi.org/10.1016/j.cmet.2013.09.002

Profiling of glucose-sensing neurons reveals that ghrh neurons are activated by hypoglycemia. / Stanley, Sarah; Domingos, Ana I.; Kelly, Leah; Garfield, Alastair; Damanpour, Shadi; Heisler, Lora; Friedman, Jeffrey.

In: Cell Metabolism, Vol. 18, No. 4, 01.10.2013, p. 596-607.

Research output: Contribution to journalArticle

Stanley, S, Domingos, AI, Kelly, L, Garfield, A, Damanpour, S, Heisler, L & Friedman, J 2013, 'Profiling of glucose-sensing neurons reveals that ghrh neurons are activated by hypoglycemia' Cell Metabolism, vol. 18, no. 4, pp. 596-607. https://doi.org/10.1016/j.cmet.2013.09.002
Stanley, Sarah ; Domingos, Ana I. ; Kelly, Leah ; Garfield, Alastair ; Damanpour, Shadi ; Heisler, Lora ; Friedman, Jeffrey. / Profiling of glucose-sensing neurons reveals that ghrh neurons are activated by hypoglycemia. In: Cell Metabolism. 2013 ; Vol. 18, No. 4. pp. 596-607.
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AU - Heisler, Lora

AU - Friedman, Jeffrey

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N2 - 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.

AB - 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.

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