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

被引:441
作者
Yamamoto, H
Lee, CE
Marcus, JN
Williams, TD
Overton, JM
Lopez, ME
Hollenberg, AN
Baggio, L
Saper, CB
Drucker, DJ
Elmquist, JK
机构
[1] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02215 USA
[2] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA
[3] Florida State Univ, Program Neurosci, Dept Nutr Food & Exercise Sci, Tallahassee, FL 32306 USA
[4] Toronto Gen Hosp, Dept Med, Toronto, ON M5G 1L7, Canada
[5] Univ Toronto, Banting & Best Diabet Ctr, Toronto, ON M5G 1L5, Canada
[6] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA
关键词
D O I
10.1172/JCI200215595
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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 bra-in, 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.
引用
收藏
页码:43 / 52
页数:10
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