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

Hiroshi Yamamoto, Charlotte E. Lee, Jacob N. Marcus, Todd D. Williams, J. Michael Overton, Marisol E. Lopez, Anthony N. Hollenberg, Laurie Baggio, Clifford B. Saper, Daniel J. Drucker, Joel K. Elmquist

Research output: Contribution to journalArticle

408 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)43-52
Number of pages10
JournalJournal of Clinical Investigation
Volume110
Issue number1
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Medicine(all)

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    Yamamoto, H., Lee, C. E., Marcus, J. N., Williams, T. D., Michael Overton, J., Lopez, M. E., Hollenberg, A. N., Baggio, L., Saper, C. B., Drucker, D. J., & Elmquist, J. K. (2002). Glucagon-like peptide-1 receptor stimulation increases blood pressure and heart rate and activates autonomic regulatory neurons. Journal of Clinical Investigation, 110(1), 43-52. https://doi.org/10.1172/JCI0215595