Related Experiment Video
Updated: May 5, 2026

Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice
Published on: November 16, 2011
Oxyntomodulin increases intrinsic heart rate through the glucagon receptor
Auyon Mukharji1, Daniel J Drucker, Maureen J Charron
1Department of Biology, Williams College Williamstown, Massachusetts.
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 beta-blockers to elevate HR in clinical conditions.
Related Concept Videos
Regulation of Heart Rates
The SNS increases heart rate through the release of norepinephrine and epinephrine, which act on beta-1 adrenergic receptors in the heart. This action increases the rate of depolarization in the sinoatrial (SA) node, the heart's...
Hormones Regulating Blood Glucose
In addition to accelerating glucose uptake and utilization, insulin has...
Glucagon-like Receptor Agonists
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
Factors Influencing Heart Rate
Let us explore the significant factors affecting heart rate, including age, body temperature, posture, acute pain, chemical influences,...
G-Protein Gated Ion Channels
Sensory...
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
Insulin and C-peptide are...

