GLP-1 receptor stimulation depresses heart rate variability and inhibits neurotransmission to cardiac vagal neurons

Kathleen J. Griffioen, Ruiqian Wan, Eitan Okun, Xin Wang, Mary Rachael Lovett-Barr, Yazhou Li, Mohamed R. Mughal, David Mendelowitz, Mark P. Mattson

Research output: Contribution to journalArticlepeer-review

76 Scopus citations


Aims Glucagon-like peptide 1 (GLP-1) is an incretin hormone released from the gut in response to food intake. Whereas GLP-1 acts in the periphery to inhibit glucagon secretion and stimulate insulin release, it also acts in the central nervous system to mediate autonomic control of feeding, body temperature, and cardiovascular function. Because of its role as an incretin hormone, GLP-1 receptor analogs are used as a treatment for type 2 diabetes. Central or peripheral administration of GLP-1 increases blood pressure and heart rate, possibly by activating brainstem autonomic nuclei and increasing vagus nerve activity. However, the mechanism(s) by which GLP-1 receptor stimulation affects cardiovascular function are unknown. We used the long-lasting GLP-1 receptor agonist Exendin-4 (Ex-4) to test the hypothesis that GLP-1 signalling modulates central parasympathetic control of heart rate.Methods and results Using a telemetry system, we assessed heart rate in mice during central Ex-4 administration. Heart rate was increased by both acute and chronic central Ex-4 administration. Spectral analysis indicated that the high frequency and low frequency powers of heart rate variability were diminished by Ex-4 treatment. Finally, Ex-4 decreased both excitatory glutamatergic and inhibitory glycinergic neurotransmission to preganglionic parasympathetic cardiac vagal neurons. Conclusion These data suggest that central GLP-1 receptor stimulation diminishes parasympathetic modulation of the heart thereby increasing heart rate.

Original languageEnglish
Pages (from-to)72-78
Number of pages7
JournalCardiovascular Research
Issue number1
StatePublished - 1 Jan 2011
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by NIH grant HL59895 to D.M. and the Intramural Research Program of the National Institute on Aging.


  • Glucagon-like peptide 1
  • Medulla
  • Nucleus ambiguus
  • Parasympathetic
  • Vagus


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