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

Cell Metab. 2013 Oct 1;18(4):596-607. doi: 10.1016/j.cmet.2013.09.002.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Ribosomal Proteins
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Growth Hormone-Releasing Hormone
  • Deoxyglucose
  • Glucokinase
  • Glucose