山本 寛 先生
A role of central Glucagon-like peptide-1 in regulating sympathetic outflow
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 has diverse central actions including inhibition of food and water intake, gastric emptying, and stimulation of neuroendocrine responses characteristic of visceral illness. 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.
In this study, we found that both iv and icv administration of GLP-1 receptor (GLP-1R) agonists increase blood pressure and heart rate, and induce Fos-like immunoreactivity (Fos-IR) 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.