help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gros, R.
Right arrow Articles by Husain, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gros, R.
Right arrow Articles by Husain, M.
Endocrinology Vol. 144, No. 6 2242-2252
Copyright © 2003 by The Endocrine Society

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

Robert Gros, Xiaomang You, Laurie L. Baggio, M. Golam Kabir, Al Muktafi Sadi, Imran N. Mungrue, Thomas G. Parker, Qingling Huang, Daniel J. Drucker and Mansoor Husain

Heart and Stroke Richard Lewar Center of Excellence (R.G., X.Y., M.G.K., A.M.S., I.N.M., T.G.P., M.H.), University of Toronto; Division of Cellular and Molecular Biology (R.G., X.Y., M.G.K., A.M.S., I.N.M., T.G.P., M.H.), Toronto General Hospital Research Institute; and Department of Medicine, Banting and Best Diabetes Centre (L.L.B., Q.H., D.J.D.), Toronto General Hospital, University of Toronto, Toronto, Canada M5G 2C4

Address all correspondence and requests for reprints to: Mansoor Husain, M.D., Toronto General Hospital, 200 Elizabeth Street, EN12-221, Toronto, Ontario, Canada M5G 2C4. E-mail: mansoor.husain{at}utoronto.ca.

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.




This article has been cited by other articles:


Home page
 Pharmacol. Rev.Home page
W. Kim and J. M. Egan
The Role of Incretins in Glucose Homeostasis and Diabetes Treatment
Pharmacol. Rev., December 1, 2008; 60(4): 470 - 512.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. Maida, J. A. Lovshin, L. L. Baggio, and D. J. Drucker
The Glucagon-Like Peptide-1 Receptor Agonist Oxyntomodulin Enhances {beta}-Cell Function but Does Not Inhibit Gastric Emptying in Mice
Endocrinology, November 1, 2008; 149(11): 5670 - 5678.
[Abstract] [Full Text] [PDF]

Home page
 Circ Heart FailHome page
D. J. Hausenloy and D. M. Yellon
GLP-1 Therapy: Beyond Glucose Control
Circ Heart Fail, September 1, 2008; 1(3): 147 - 149.
[Full Text] [PDF]

Home page
 Circ Heart FailHome page
I. Poornima, S. B. Brown, S. Bhashyam, P. Parikh, H. Bolukoglu, and R. P. Shannon
Chronic Glucagon-Like Peptide-1 Infusion Sustains Left Ventricular Systolic Function and Prolongs Survival in the Spontaneously Hypertensive, Heart Failure-Prone Rat
Circ Heart Fail, September 1, 2008; 1(3): 153 - 160.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
K. Ban, M. H. Noyan-Ashraf, J. Hoefer, S.-S. Bolz, D. J. Drucker, and M. Husain
Cardioprotective and Vasodilatory Actions of Glucagon-Like Peptide 1 Receptor Are Mediated Through Both Glucagon-Like Peptide 1 Receptor-Dependent and -Independent Pathways
Circulation, May 6, 2008; 117(18): 2340 - 2350.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
A. Basu, N. Charkoudian, W. Schrage, R. A. Rizza, R. Basu, and M. J. Joyner
Beneficial effects of GLP-1 on endothelial function in humans: dampening by glyburide but not by glimepiride
Am J Physiol Endocrinol Metab, November 1, 2007; 293(5): E1289 - E1295.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
J. J. Holst
The Physiology of Glucagon-like Peptide 1
Physiol Rev, October 1, 2007; 87(4): 1409 - 1439.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
L. B. Knudsen, D. Kiel, M. Teng, C. Behrens, D. Bhumralkar, J. T. Kodra, J. J. Holst, C. B. Jeppesen, M. D. Johnson, J. C. de Jong, et al.
From the Cover: Small-molecule agonists for the glucagon-like peptide 1 receptor
PNAS, January 16, 2007; 104(3): 937 - 942.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
M. C. Riddle and D. J. Drucker
Emerging Therapies Mimicking the Effects of Amylin and Glucagon-Like Peptide 1
Diabetes Care, February 1, 2006; 29(2): 435 - 449.
[Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
L. A. Nikolaidis, D. Elahi, Y.-T. Shen, and R. P. Shannon
Active metabolite of GLP-1 mediates myocardial glucose uptake and improves left ventricular performance in conscious dogs with dilated cardiomyopathy
Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2401 - H2408.
[Abstract] [Full Text] [PDF]

Home page
 PhysiologyHome page
E. M Sinclair and D. J. Drucker
Proglucagon-Derived Peptides: Mechanisms of Action and Therapeutic Potential
Physiology, October 1, 2005; 20(5): 357 - 365.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
A. K. Bose, M. M. Mocanu, R. D. Carr, C. L. Brand, and D. M. Yellon
Glucagon-like Peptide 1 Can Directly Protect the Heart Against Ischemia/Reperfusion Injury
Diabetes, January 1, 2005; 54(1): 146 - 151.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
L. L. Baggio, Q. Huang, T. J. Brown, and D. J. Drucker
A Recombinant Human Glucagon-Like Peptide (GLP)-1-Albumin Protein (Albugon) Mimics Peptidergic Activation of GLP-1 Receptor-Dependent Pathways Coupled With Satiety, Gastrointestinal Motility, and Glucose Homeostasis
Diabetes, September 1, 2004; 53(9): 2492 - 2500.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
L. L. Yang, R. Gros, M. G. Kabir, A. Sadi, A. I. Gotlieb, M. Husain, and D. J. Stewart
Conditional Cardiac Overexpression of Endothelin-1 Induces Inflammation and Dilated Cardiomyopathy in Mice
Circulation, January 20, 2004; 109(2): 255 - 261.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
D. J. Drucker
Enhancing Incretin Action for the Treatment of Type 2 Diabetes
Diabetes Care, October 1, 2003; 26(10): 2929 - 2940.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2003 by The Endocrine Society