Oxyntomodulin increases intrinsic heart rate through the glucagon receptor

Auyon Mukharji, Daniel J. Drucker, Maureen J. Charron, Steven J. Swoap

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Two hormones from the gastrointestinal tract, glucagon and oxyntomodulin (OXM), vigorously elevate the intrinsic heart rate (IHR) of mice. We have previously shown that OXM influences murine heart rate (HR) independent of the glucagon-like peptide 1 (GLP-1) receptor. Here, we demonstrate using radiotelemetry in mice deficient in the glucagon receptor (Gcgr /) that both OXM and glucagon require the glucagon receptor for their chronotropic effects on the heart. Furthermore, we found that other hormones associated with hunger and satiety (ghrelin, leptin, and PYY3-36) had no effect on IHR, while cholecystokinin moderately elevated the IHR. Finally, the resting HR of Gcgr / mice was higher than in control mice (Gcgr +/+ and Gcgr +/) at thermal neutral temperature (30°C). Using atropine, we demonstrated that Gcgr / mice have diminished parasympathetic (PNS) influence of the heart at this temperature. Gcgr / mice displayed a normal bradycardia as compared to controls in response to administration of either methacholine (to activate the muscarinic acetylcholine receptor) or methoxamine (to activate the baroreflex through agonism of the α1 adrenergic receptor agonist) suggesting that vagal pathways are intact in the Gcgr / mice. As OXM is an agonist of the GLP-1 receptor and Gcgr with antidiabetic activity, we suggest OXM may be an alternative to glucagon in the treatment of overdose of betablockers to elevate HR in clinical conditions.

Original languageEnglish (US)
Article numbere00112
JournalPhysiological Reports
Volume1
Issue number5
DOIs
StatePublished - 2013

Fingerprint

Oxyntomodulin
Glucagon Receptors
Heart Rate
Glucagon
Hormones
Methoxamine
Adrenergic Agonists
Ghrelin
Temperature
Hunger
Methacholine Chloride
Baroreflex
Cholecystokinin
Muscarinic Receptors
Bradycardia
Leptin
Atropine
Hypoglycemic Agents
Gastrointestinal Tract
Hot Temperature

Keywords

  • Beta block
  • GLP-1
  • OXM
  • Sympathetic nervous system

ASJC Scopus subject areas

  • Physiology (medical)
  • Physiology

Cite this

Oxyntomodulin increases intrinsic heart rate through the glucagon receptor. / Mukharji, Auyon; Drucker, Daniel J.; Charron, Maureen J.; Swoap, Steven J.

In: Physiological Reports, Vol. 1, No. 5, e00112, 2013.

Research output: Contribution to journalArticle

Mukharji, Auyon ; Drucker, Daniel J. ; Charron, Maureen J. ; Swoap, Steven J. / Oxyntomodulin increases intrinsic heart rate through the glucagon receptor. In: Physiological Reports. 2013 ; Vol. 1, No. 5.
@article{84b30fd8dd634a719ec74b2f80ab9d6c,
title = "Oxyntomodulin increases intrinsic heart rate through the glucagon receptor",
abstract = "Two hormones from the gastrointestinal tract, glucagon and oxyntomodulin (OXM), vigorously elevate the intrinsic heart rate (IHR) of mice. We have previously shown that OXM influences murine heart rate (HR) independent of the glucagon-like peptide 1 (GLP-1) receptor. Here, we demonstrate using radiotelemetry in mice deficient in the glucagon receptor (Gcgr /) that both OXM and glucagon require the glucagon receptor for their chronotropic effects on the heart. Furthermore, we found that other hormones associated with hunger and satiety (ghrelin, leptin, and PYY3-36) had no effect on IHR, while cholecystokinin moderately elevated the IHR. Finally, the resting HR of Gcgr / mice was higher than in control mice (Gcgr +/+ and Gcgr +/) at thermal neutral temperature (30°C). Using atropine, we demonstrated that Gcgr / mice have diminished parasympathetic (PNS) influence of the heart at this temperature. Gcgr / mice displayed a normal bradycardia as compared to controls in response to administration of either methacholine (to activate the muscarinic acetylcholine receptor) or methoxamine (to activate the baroreflex through agonism of the α1 adrenergic receptor agonist) suggesting that vagal pathways are intact in the Gcgr / mice. As OXM is an agonist of the GLP-1 receptor and Gcgr with antidiabetic activity, we suggest OXM may be an alternative to glucagon in the treatment of overdose of betablockers to elevate HR in clinical conditions.",
keywords = "Beta block, GLP-1, OXM, Sympathetic nervous system",
author = "Auyon Mukharji and Drucker, {Daniel J.} and Charron, {Maureen J.} and Swoap, {Steven J.}",
year = "2013",
doi = "10.1002/phy2.112",
language = "English (US)",
volume = "1",
journal = "Physiological Reports",
issn = "2051-817X",
publisher = "John Wiley and Sons Inc.",
number = "5",

}

TY - JOUR

T1 - Oxyntomodulin increases intrinsic heart rate through the glucagon receptor

AU - Mukharji, Auyon

AU - Drucker, Daniel J.

AU - Charron, Maureen J.

AU - Swoap, Steven J.

PY - 2013

Y1 - 2013

N2 - Two hormones from the gastrointestinal tract, glucagon and oxyntomodulin (OXM), vigorously elevate the intrinsic heart rate (IHR) of mice. We have previously shown that OXM influences murine heart rate (HR) independent of the glucagon-like peptide 1 (GLP-1) receptor. Here, we demonstrate using radiotelemetry in mice deficient in the glucagon receptor (Gcgr /) that both OXM and glucagon require the glucagon receptor for their chronotropic effects on the heart. Furthermore, we found that other hormones associated with hunger and satiety (ghrelin, leptin, and PYY3-36) had no effect on IHR, while cholecystokinin moderately elevated the IHR. Finally, the resting HR of Gcgr / mice was higher than in control mice (Gcgr +/+ and Gcgr +/) at thermal neutral temperature (30°C). Using atropine, we demonstrated that Gcgr / mice have diminished parasympathetic (PNS) influence of the heart at this temperature. Gcgr / mice displayed a normal bradycardia as compared to controls in response to administration of either methacholine (to activate the muscarinic acetylcholine receptor) or methoxamine (to activate the baroreflex through agonism of the α1 adrenergic receptor agonist) suggesting that vagal pathways are intact in the Gcgr / mice. As OXM is an agonist of the GLP-1 receptor and Gcgr with antidiabetic activity, we suggest OXM may be an alternative to glucagon in the treatment of overdose of betablockers to elevate HR in clinical conditions.

AB - Two hormones from the gastrointestinal tract, glucagon and oxyntomodulin (OXM), vigorously elevate the intrinsic heart rate (IHR) of mice. We have previously shown that OXM influences murine heart rate (HR) independent of the glucagon-like peptide 1 (GLP-1) receptor. Here, we demonstrate using radiotelemetry in mice deficient in the glucagon receptor (Gcgr /) that both OXM and glucagon require the glucagon receptor for their chronotropic effects on the heart. Furthermore, we found that other hormones associated with hunger and satiety (ghrelin, leptin, and PYY3-36) had no effect on IHR, while cholecystokinin moderately elevated the IHR. Finally, the resting HR of Gcgr / mice was higher than in control mice (Gcgr +/+ and Gcgr +/) at thermal neutral temperature (30°C). Using atropine, we demonstrated that Gcgr / mice have diminished parasympathetic (PNS) influence of the heart at this temperature. Gcgr / mice displayed a normal bradycardia as compared to controls in response to administration of either methacholine (to activate the muscarinic acetylcholine receptor) or methoxamine (to activate the baroreflex through agonism of the α1 adrenergic receptor agonist) suggesting that vagal pathways are intact in the Gcgr / mice. As OXM is an agonist of the GLP-1 receptor and Gcgr with antidiabetic activity, we suggest OXM may be an alternative to glucagon in the treatment of overdose of betablockers to elevate HR in clinical conditions.

KW - Beta block

KW - GLP-1

KW - OXM

KW - Sympathetic nervous system

UR - http://www.scopus.com/inward/record.url?scp=85009067362&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85009067362&partnerID=8YFLogxK

U2 - 10.1002/phy2.112

DO - 10.1002/phy2.112

M3 - Article

VL - 1

JO - Physiological Reports

JF - Physiological Reports

SN - 2051-817X

IS - 5

M1 - e00112

ER -