Profiling of Glucose-Sensing Neurons Reveals that GHRH Neurons Are Activated by Hypoglycemia
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...
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| Veröffentlicht in: | Cell metabolism 2013-10, Vol.18 (4), p.596-607 |
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| creator | Stanley, Sarah Domingos, Ana I. Kelly, Leah Garfield, Alastair Damanpour, Shadi Heisler, Lora Friedman, Jeffrey |
| description | 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.
•Transcriptional profiling method for cells marked by genes expressed at low levels•Generation of mice with lox-stop-lox EGFP-tagged ribosomal protein•Validation of method by profiling glucose-sensing neurons expressing glucokinase•Identification of previously unknown glucose-sensing populations |
| doi_str_mv | 10.1016/j.cmet.2013.09.002 |
| format | Article |
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•Transcriptional profiling method for cells marked by genes expressed at low levels•Generation of mice with lox-stop-lox EGFP-tagged ribosomal protein•Validation of method by profiling glucose-sensing neurons expressing glucokinase•Identification of previously unknown glucose-sensing populations</description><subject>Animals</subject><subject>Deoxyglucose - pharmacology</subject><subject>Gene Expression Profiling</subject><subject>Glucokinase - genetics</subject><subject>Glucokinase - metabolism</subject><subject>Glucose - pharmacology</subject><subject>Green Fluorescent Proteins - genetics</subject><subject>Green Fluorescent Proteins - metabolism</subject><subject>Growth Hormone-Releasing Hormone - metabolism</subject><subject>Hypoglycemia - metabolism</subject><subject>Hypoglycemia - pathology</subject><subject>Hypothalamus - metabolism</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Neurons - drug effects</subject><subject>Neurons - metabolism</subject><subject>Ribosomal Proteins - genetics</subject><subject>Ribosomal Proteins - metabolism</subject><issn>1550-4131</issn><issn>1932-7420</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1Lw0AQhhdR_Kj-AQ-So5fE2Y-kLngpRVuhqFS9CUuyO6lbkmzdTQr996a09uhpltnnfWEeQq4pJBRodrdMdI1twoDyBGQCwI7IOZWcxUPB4Lh_pynEgnJ6Ri5CWALwjEt-Ss6YAMmze3ZOvt68K21lm0XkymhSddoFjN-xCdvVC3beNSGa4xrzKkTtd95Gk-l8evgZeYxGurXrvEUTFZtoulm5RbXRWNv8kpyUfQyv9nNAPp8eP8bTePY6eR6PZrEWnLdxygvggpWmAChNCbmkQ6F1KgueSjE0hcESs9RARgWTnOZDTTWTUgBQVgjBB-R217vy7qfD0KraBo1VlTfouqBoloGAe5rJHmU7VHsXgsdSrbytc79RFNTWqlqqrVW1tapAqt5qH7rZ93dFjeYQ-dPYAw87APsr1xa9Ctpio9FYj7pVxtn_-n8Bd8SH2Q</recordid><startdate>20131001</startdate><enddate>20131001</enddate><creator>Stanley, Sarah</creator><creator>Domingos, Ana I.</creator><creator>Kelly, Leah</creator><creator>Garfield, Alastair</creator><creator>Damanpour, Shadi</creator><creator>Heisler, Lora</creator><creator>Friedman, Jeffrey</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope></search><sort><creationdate>20131001</creationdate><title>Profiling of Glucose-Sensing Neurons Reveals that GHRH Neurons Are Activated by Hypoglycemia</title><author>Stanley, Sarah ; Domingos, Ana I. ; Kelly, Leah ; Garfield, Alastair ; Damanpour, Shadi ; Heisler, Lora ; Friedman, Jeffrey</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c433t-53b0342fdb00fdf0a9174cc59b35947dbdefe65d06142931a7c1c29940012b443</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Deoxyglucose - pharmacology</topic><topic>Gene Expression Profiling</topic><topic>Glucokinase - genetics</topic><topic>Glucokinase - metabolism</topic><topic>Glucose - pharmacology</topic><topic>Green Fluorescent Proteins - genetics</topic><topic>Green Fluorescent Proteins - metabolism</topic><topic>Growth Hormone-Releasing Hormone - metabolism</topic><topic>Hypoglycemia - metabolism</topic><topic>Hypoglycemia - pathology</topic><topic>Hypothalamus - metabolism</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Neurons - drug effects</topic><topic>Neurons - metabolism</topic><topic>Ribosomal Proteins - genetics</topic><topic>Ribosomal Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stanley, Sarah</creatorcontrib><creatorcontrib>Domingos, Ana I.</creatorcontrib><creatorcontrib>Kelly, Leah</creatorcontrib><creatorcontrib>Garfield, Alastair</creatorcontrib><creatorcontrib>Damanpour, Shadi</creatorcontrib><creatorcontrib>Heisler, Lora</creatorcontrib><creatorcontrib>Friedman, Jeffrey</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><jtitle>Cell metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stanley, Sarah</au><au>Domingos, Ana I.</au><au>Kelly, Leah</au><au>Garfield, Alastair</au><au>Damanpour, Shadi</au><au>Heisler, Lora</au><au>Friedman, Jeffrey</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Profiling of Glucose-Sensing Neurons Reveals that GHRH Neurons Are Activated by Hypoglycemia</atitle><jtitle>Cell metabolism</jtitle><addtitle>Cell Metab</addtitle><date>2013-10-01</date><risdate>2013</risdate><volume>18</volume><issue>4</issue><spage>596</spage><epage>607</epage><pages>596-607</pages><issn>1550-4131</issn><eissn>1932-7420</eissn><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.
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present); Cell Press Free Archives; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Deoxyglucose - pharmacology Gene Expression Profiling Glucokinase - genetics Glucokinase - metabolism Glucose - pharmacology Green Fluorescent Proteins - genetics Green Fluorescent Proteins - metabolism Growth Hormone-Releasing Hormone - metabolism Hypoglycemia - metabolism Hypoglycemia - pathology Hypothalamus - metabolism Male Mice Mice, Inbred C57BL Mice, Transgenic Neurons - drug effects Neurons - metabolism Ribosomal Proteins - genetics Ribosomal Proteins - metabolism |
| title | Profiling of Glucose-Sensing Neurons Reveals that GHRH Neurons Are Activated by Hypoglycemia |
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