ZFIN ID: ZDB-PUB-200128-1
Global Transcriptomic Analysis of Zebrafish Glucagon Receptor Mutant Reveals Its Regulated Metabolic Network
Kang, Q., Hu, M., Jia, J., Bai, X., Liu, C., Wu, Z., Chen, W., Li, M.
Date: 2020
Source: International Journal of Molecular Sciences   21(3): (Journal)
Registered Authors: Chen, Wenbiao, Li, Mingyu
Keywords: RNA sequencing, diabetes, glucagon receptor, metabolic network, zebrafish
MeSH Terms:
  • Animals
  • Gene Expression Profiling/methods
  • Glucose/genetics
  • Glucose/metabolism
  • Liver/metabolism
  • Liver/physiology
  • Metabolic Networks and Pathways/genetics*
  • Receptors, Glucagon/genetics*
  • Receptors, Glucagon/metabolism
  • Signal Transduction/genetics
  • Transcriptome/genetics*
  • Zebrafish/genetics*
  • Zebrafish/metabolism
PubMed: 31979106 Full text @ Int. J. Mol. Sci.
The glucagon receptor (GCGR) is a G-protein-coupled receptor (GPCR) that mediates the activity of glucagon. Disruption of GCGR results in many metabolic alterations, including increased glucose tolerance, decreased adiposity, hypoglycemia, and pancreatic α-cell hyperplasia. To better understand the global transcriptomic changes resulting from GCGR deficiency, we performed whole-organism RNA sequencing analysis in wild type and gcgr-deficient zebrafish. We found that the expression of 1645 genes changes more than two-fold among mutants. Most of these genes are related to metabolism of carbohydrates, lipids, and amino acids. Genes related to fatty acid β-oxidation, amino acid catabolism, and ureagenesis are often downregulated. Among gcrgr-deficient zebrafish, we experimentally confirmed increases in lipid accumulation in the liver and whole-body glucose uptake, as well as a modest decrease in total amino acid content. These results provide new information about the global metabolic network that GCGR signaling regulates in addition to a better understanding of the receptor's physiological functions.