Cardiac function in mice lacking the glucagon-like peptide-1 receptor.
Glucagon-like peptide-1 (GLP-1) acts via its G protein-coupled receptor (GLP-1R) to regulate blood glucose. Although the GLP-1R is widely expressed in peripheral tissues, including the heart, and exogenous GLP-1 administration increases heart rate and blood pressure in rodents, the physiological importance of GLP-1R action in the cardiovascular system remains unclear. We now show that 2-month-old mice with genetic deletion of the GLP-1R (GLP-1R(-/-)) exhibit reduced resting heart rate and elevated left ventricular (LV) end diastolic pressure compared with CD-1 wild-type controls. At the age of 5 months, echocardiography and histology demonstrate increased LV thickness in GLP-1R(-/-) mice. Although baseline hemodynamic parameters of GLP-1R(-/-) did not differ significantly from those of wild type, GLP-1R(-/-) mice displayed impaired LV contractility and diastolic function after insulin administration. The defective cardiovascular response to insulin was not attributable to a generalized defect in the stress response, because GLP-1R(-/-) mice responded appropriately to insulin with increased c-fos expression in the hypothalamus and increased circulating levels of glucagon and epinephrine. Furthermore, LV contractility after exogenous epinephrine infusion was also reduced in GLP-1R(-/-) mice. These findings provide new evidence implicating an essential role for GLP-1R in the control of murine cardiac structure and function in vivo.
Gros
Robert
R
Heart and Stroke Richard Lewar Center of Excellence, University of Toronto, Canada.
You
Xiaomang
X
Baggio
Laurie L
LL
Kabir
M Golam
MG
Sadi
Al Muktafi
AM
Mungrue
Imran N
IN
Parker
Thomas G
TG
Huang
Qingling
Q
Drucker
Daniel J
DJ
Husain
Mansoor
M
D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D004452:Echocardiography; D000067757:Glucagon-Like Peptide-1 Receptor; D006321:Heart / Q000502:physiology*; D006331:Heart Diseases / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D006339:Heart Rate; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009206:Myocardium / Q000473:pathology; D018027:Receptors, Glucagon / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology*; D013312:Stress, Physiological / Q000503:physiopathology; D017725:Ventricular Pressure
C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D018027:Receptors, Glucagon