Distribution of pre-pro-glucagon and glucagon-like peptide-1 receptor messenger RNAs in the rat central nervous system

J Comp Neurol. 1999 Jan 11;403(2):261-80. doi: 10.1002/(sici)1096-9861(19990111)403:2<261::aid-cne8>3.0.co;2-5.


Glucagon-like peptide-1 (GLP-1) is derived from the peptide precursor pre-pro-glucagon (PPG) by enzymatic cleavage and acts via its receptor, glucagon-like peptide-1 receptor (GLP-1R). By using riboprobes complementary to PPG and GLP-1R, we described the distribution of PPG and GLP-1R messenger RNAs (mRNAs) in the central nervous system of the rat. PPG mRNA-expressing perikarya were restricted to the nucleus of the solitary tact or to the dorsal and ventral medulla and olfactory bulb. GLP-1R mRNA was detected in numerous brain regions, including the mitral cell layer of the olfactory bulb; temporal cortex; caudal hippocampus; lateral septum; amygdala; nucleus accumbens; ventral pallium; nucleus basalis Meynert; bed nucleus of the stria terminalis; preoptic area; paraventricular, supraoptic, arcuate, and dorsomedial nuclei of the hypothalamus; lateral habenula; zona incerta; substantia innominata; posterior thalamic nuclei; ventral tegmental area; dorsal tegmental, posterodorsal tegmental, and interpeduncular nuclei; substantia nigra, central gray; raphe nuclei; parabrachial nuclei; locus ceruleus, nucleus of the solitary tract; area postrema; dorsal nucleus of the vagus; lateral reticular nucleus; and spinal cord. These studies, in addition to describing the sites of GLP-1 and GLP-1R synthesis, suggest that the efferent connections from the nucleus of the solitary tract are more widespread than previously reported. Although the current role of GLP-1 in regulating neuronal physiology is not known, these studies provide detailed information about the sites of GLP-1 synthesis and potential sites of action, an important first step in evaluating the function of GLP-1 in the brain. The widespread distribution of GLP-1R mRNA-containing cells strongly suggests that GLP-1 not only functions as a satiety factor but also acts as a neurotransmitter or neuromodulator in anatomically and functionally distinct areas of the central nervous system.

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / metabolism*
  • Female
  • Glucagon / genetics*
  • Glucagon-Like Peptide-1 Receptor
  • In Situ Hybridization
  • Islets of Langerhans / cytology
  • Islets of Langerhans / metabolism
  • Neurons / cytology
  • Neurons / metabolism
  • Organ Specificity
  • Proglucagon
  • Protein Precursors / genetics*
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glucagon / genetics*
  • Spinal Cord / cytology
  • Spinal Cord / metabolism*


  • Glp1r protein, rat
  • Glucagon-Like Peptide-1 Receptor
  • Protein Precursors
  • RNA, Messenger
  • Receptors, Glucagon
  • Proglucagon
  • Glucagon