Glucagon-like peptide-1 receptor stimulation increases blood pressure and heart rate and activates autonomic regulatory neurons

J Clin Invest. 2002 Jul;110(1):43-52. doi: 10.1172/JCI15595.

Abstract

Glucagon-like peptide-1 (GLP-1) released from the gut functions as an incretin that stimulates insulin secretion. GLP-1 is also a brain neuropeptide that controls feeding and drinking behavior and gastric emptying and elicits neuroendocrine responses including development of conditioned taste aversion. Although GLP-1 receptor (GLP-1R) agonists are under development for the treatment of diabetes, GLP-1 administration may increase blood pressure and heart rate in vivo. We report here that centrally and peripherally administered GLP-1R agonists dose-dependently increased blood pressure and heart rate. GLP-1R activation induced c-fos expression in the adrenal medulla and neurons in autonomic control sites in the rat brain, including medullary catecholamine neurons providing input to sympathetic preganglionic neurons. Furthermore, GLP-1R agonists rapidly activated tyrosine hydroxylase transcription in brainstem catecholamine neurons. These findings suggest that the central GLP-1 system represents a regulator of sympathetic outflow leading to downstream activation of cardiovascular responses in vivo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenal Glands / anatomy & histology
  • Adrenal Glands / drug effects
  • Adrenal Glands / metabolism
  • Animals
  • Autonomic Nervous System / drug effects
  • Autonomic Nervous System / physiology*
  • Blood Pressure / drug effects
  • Blood Pressure / physiology*
  • Brain / anatomy & histology
  • Brain / drug effects
  • Brain / metabolism
  • Catecholamines / metabolism
  • Exenatide
  • Glucagon-Like Peptide-1 Receptor
  • Heart Rate / drug effects
  • Heart Rate / physiology*
  • Male
  • Models, Neurological
  • Neural Pathways / drug effects
  • Neural Pathways / physiology
  • Peptides / pharmacology
  • Proto-Oncogene Proteins c-fos / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glucagon / agonists*
  • Receptors, Glucagon / physiology*
  • Spinal Cord / anatomy & histology
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism
  • Venoms*

Substances

  • Catecholamines
  • Glp1r protein, rat
  • Glucagon-Like Peptide-1 Receptor
  • Peptides
  • Proto-Oncogene Proteins c-fos
  • Receptors, Glucagon
  • Venoms
  • Exenatide