Glucagon-like peptide-1 receptor stimulation increases blood pressure and heart rate and activates autonomic regulatory neurons.
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.
Yamamoto
Hiroshi
H
Department of Medicine and Division of Endocrinology, Beth Israel Deaconess Medical Center, Harvard Medical School, 99 Brookline Avenue, Boston, MA 02215, USA.
Lee
Charlotte E
CE
Marcus
Jacob N
JN
Williams
Todd D
TD
Overton
J Michael
JM
Lopez
Marisol E
ME
Hollenberg
Anthony N
AN
Baggio
Laurie
L
Saper
Clifford B
CB
Drucker
Daniel J
DJ
Elmquist
Joel K
JK
D000311:Adrenal Glands / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D000077270:Exenatide; D000067757:Glucagon-Like Peptide-1 Receptor; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008959:Models, Neurological; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D010455:Peptides / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018027:Receptors, Glucagon / Q000819:agonists* / Q000502:physiology*; D013116:Spinal Cord / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D014688:Venoms
D002395:Catecholamines; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D010455:Peptides; D016760:Proto-Oncogene Proteins c-fos; D018027:Receptors, Glucagon; D014688:Venoms; D000077270:Exenatide