Ghrelin affects carbohydrate-glycogen metabolism via insulin inhibition and glucagon stimulation in the zebrafish (Danio rerio) brain

Shelly A. Cruz, Yung Che Tseng, Hiroyuki Kaiya, Pung Pung Hwang

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Carbohydrate-glycogen metabolism (CGM) is critical for emergency energy supplies in the central nervous system (CNS). Ghrelin (GHRL) in pancreas is known to significantly regulate a dominant player in CGM, insulin (INS). However, its regulatory effect on extrapancreatic INS synthesis is yet unknown. In this study, we used adult zebrafish to elucidate the expression and role of zebrafish GHRL (zGHRL) in genes primarily involved in the brain's CGM. Results showed that zebrafish brain expressed zghrl and its receptor, growth hormone secretagogue-receptor (GHS-R: zghs-r1a and zghs-r2a), according to RT-PCR and in situ hybridization. Protein localization coupled with mRNA spatial expression further verified zGHRL's presence in the brain. For the in vivo study, significant increases in zghs-r1a and zghs-r2a synthesis were observed after injection of synthetic peptide goldfish GHRL-12 (gGHRL) using brain templates analyzed by quantitative real-time PCR (qPCR). Ligand-receptor synthesis of INS (zinsa; zins-r1 and zins-r2) significantly decreased, while glucagon (GCG) (zgcgb1 and zgcgb2; zgcg-r1 and zgcg-r2) exhibited a significant transient increase. In CGM, subsequent processes indicate urgent glucose-sensing response that will balance glycogen degradation and energy storage. Taken together, these findings suggest that GHRL regulates INS synthesis by mediating its action on GHS-R in the CNS and partly involved in CGM.

Original languageEnglish
Pages (from-to)190-200
Number of pages11
JournalComparative Biochemistry and Physiology - A Molecular and Integrative Physiology
Issue number2
Publication statusPublished - 2010 Jun



  • Brain
  • Ghrelin
  • Glucagon
  • Glycogen growth hormone secretagogue receptor
  • Insulin

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology

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