title: Glucagon-like peptide-1 receptor stimulation increases blood pressure and heart rate and activates autonomic regulatory neurons.
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.
authors.affiliation: Department of Medicine and Division of Endocrinology, Beth Israel Deaconess Medical Center, Harvard Medical School, 99 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Lee
authors.forename: Jacob N
authors.initials: JN
authors.lastname: Marcus
authors.forename: Todd D
authors.initials: TD
authors.lastname: Williams
authors.forename: J Michael
authors.initials: JM
authors.lastname: Overton
authors.forename: Marisol E
authors.initials: ME
authors.lastname: Lopez
authors.forename: Anthony N
authors.initials: AN
authors.lastname: Hollenberg
authors.forename: Laurie
authors.initials: L
authors.lastname: Baggio
authors.forename: Clifford B
authors.initials: CB
authors.lastname: Saper
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Drucker
authors.forename: Joel K
authors.initials: JK
authors.lastname: Elmquist
mesh_terms: 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
chemical_list: 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