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

H Yamamoto, CE Lee, JN Marcus… - The Journal of …, 2002 - Am Soc Clin Investig
H Yamamoto, CE Lee, JN Marcus, TD Williams, JM Overton, ME Lopez, AN Hollenberg…
The Journal of clinical investigation, 2002Am Soc Clin Investig
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 …
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.
The Journal of Clinical Investigation