The expression of GLP-1 receptor mRNA and protein allows the effect of GLP-1 on glucose metabolism in the human hypothalamus and brainstem

J Neurochem. 2005 Feb;92(4):798-806. doi: 10.1111/j.1471-4159.2004.02914.x.

Abstract

In the present work, several experimental approaches were used to determine the presence of the glucagon-like peptide-1 receptor (GLP-1R) and the biological actions of its ligand in the human brain. In situ hybridization histochemistry revealed specific labelling for GLP-1 receptor mRNA in several brain areas. In addition, GLP-1R, glucose transporter isoform (GLUT-2) and glucokinase (GK) mRNAs were identified in the same cells, especially in areas of the hypothalamus involved in feeding behaviour. GLP-1R gene expression in the human brain gave rise to a protein of 56 kDa as determined by affinity cross-linking assays. Specific binding of 125I-GLP-1(7-36) amide to the GLP-1R was detected in several brain areas and was inhibited by unlabelled GLP-1(7-36) amide, exendin-4 and exendin (9-39). A further aim of this work was to evaluate cerebral-glucose metabolism in control subjects by positron emission tomography (PET), using 2-[F-18] deoxy-D-glucose (FDG). Statistical analysis of the PET studies revealed that the administration of GLP-1(7-36) amide significantly reduced (p < 0.001) cerebral glucose metabolism in hypothalamus and brainstem. Because FDG-6-phosphate is not a substrate for subsequent metabolic reactions, the lower activity observed in these areas after peptide administration may be due to reduction of the glucose transport and/or glucose phosphorylation, which should modulate the glucose sensing process in the GLUT-2- and GK-containing cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Brain Stem / metabolism*
  • Female
  • Glucagon / metabolism
  • Glucagon / physiology*
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptide-1 Receptor
  • Glucose / metabolism*
  • Humans
  • Hypothalamus / metabolism*
  • Male
  • Middle Aged
  • Peptide Fragments / metabolism
  • Peptide Fragments / physiology*
  • Protein Binding / physiology
  • Protein Precursors / metabolism
  • Protein Precursors / physiology*
  • RNA, Messenger / biosynthesis*
  • Receptors, Glucagon / biosynthesis*
  • Receptors, Glucagon / genetics*

Substances

  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Peptide Fragments
  • Protein Precursors
  • RNA, Messenger
  • Receptors, Glucagon
  • Glucagon-Like Peptide 1
  • Glucagon
  • Glucose