Cardiac Function in Mice Lacking the Glucagon-Like peptide-1 Receptor

Endocrinology. 2003 Jun;144(6):2242-52. doi: 10.1210/en.2003-0007.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Pressure
  • Body Weight
  • Echocardiography
  • Glucagon-Like Peptide-1 Receptor
  • Heart / physiology*
  • Heart Diseases / diagnostic imaging
  • Heart Diseases / pathology
  • Heart Diseases / physiopathology*
  • Heart Rate
  • Male
  • Mice
  • Mice, Mutant Strains
  • Myocardium / pathology
  • Receptors, Glucagon / genetics*
  • Signal Transduction / physiology*
  • Stress, Physiological / physiopathology
  • Ventricular Pressure

Substances

  • Glp1r protein, mouse
  • Glucagon-Like Peptide-1 Receptor
  • Receptors, Glucagon