| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
activator
1 Department of Medical Physiology, University of Tromsø, N-9037 Tromsø, Norway; 2 Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, Canada T2N 4N1; and 3 Department of Cardiology and Medicine, University of Edinburgh, Edinburgh EH8 9XF, Scotland
Hearts from diabetic
db/db mice, a model of Type 2 diabetes, exhibit
left ventricular failure and altered metabolism of exogenous substrates. Peroxisome proliferator-activated receptor-
(PPAR-) ligands reduce plasma lipid and glucose concentrations and improve insulin sensitivity in db/db mice. Consequently,
the effect of 4- to 5-wk treatment of db/db mice
with a novel PPAR- ligand (BM 17.0744; 25-38
mg · kg
1 · day1),
commencing at 8 wk of age, on ex vivo cardiac function and metabolism
was determined. Elevated plasma concentrations of glucose, fatty acids,
and triacylglycerol (34.0 ± 3.6, 2.0 ± 0.4, and 0.9 ± 0.1 mM, respectively) were reduced to normal after treatment with BM
17.0744 (10.8 ± 0.6, 1.1 ± 0.1, and 0.6 ± 0.1 mM).
Plasma insulin was also reduced significantly in treated compared with untreated db/db mice. Chronic treatment of
db/db mice with the PPAR- agonist resulted in
a 50% reduction in rates of fatty acid oxidation, with a concomitant
increase in glycolysis (1.7-fold) and glucose oxidation (2.3- fold).
Correction of the diabetes-induced abnormalities in systemic and
cardiac metabolism after BM 17.0744 treatment did not, however, improve
left ventricular contractile function.
substrate oxidation; isolated working mouse hearts
This article has been cited by other articles:
|
|
 |
|
  X. Ruan, F. Zheng, and Y. Guan PPARs and the kidney in metabolic syndrome Am J Physiol Renal Physiol, May 1, 2008; 294(5): F1032 - F1047. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. D. Abel, S. E. Litwin, and G. Sweeney Cardiac Remodeling in Obesity Physiol Rev, April 1, 2008; 88(2): 389 - 419. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. C. Noland, T. L. Woodlief, B. R. Whitfield, S. M. Manning, J. R. Evans, R. W. Dudek, R. M. Lust, and R. N. Cortright Peroxisomal-mitochondrial oxidation in a rodent model of obesity-associated insulin resistance Am J Physiol Endocrinol Metab, October 1, 2007; 293(4): E986 - E1001. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. D. Lopaschuk, C. D.L. Folmes, and W. C. Stanley Cardiac Energy Metabolism in Obesity Circ. Res., August 17, 2007; 101(4): 335 - 347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Subauste and C. F. Burant Role of FoxO1 in FFA-induced oxidative stress in adipocytes Am J Physiol Endocrinol Metab, July 1, 2007; 293(1): E159 - E164. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Boudina and E. D. Abel Diabetic Cardiomyopathy Revisited Circulation, June 26, 2007; 115(25): 3213 - 3223. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Hafstad, A. M. Khalid, O.-J. How, T. S. Larsen, and E. Aasum Glucose and insulin improve cardiac efficiency and postischemic functional recovery in perfused hearts from type 2 diabetic (db/db) mice Am J Physiol Endocrinol Metab, May 1, 2007; 292(5): E1288 - E1294. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. N. Finck The PPAR regulatory system in cardiac physiology and disease Cardiovasc Res, January 15, 2007; 73(2): 269 - 277. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. M. Borradaile, X. Han, J. D. Harp, S. E. Gale, D. S. Ory, and J. E. Schaffer Disruption of endoplasmic reticulum structure and integrity in lipotoxic cell death J. Lipid Res., December 1, 2006; 47(12): 2726 - 2737. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Li, I. S. Ali, and R. W. Currie Insulin induces myocardial protection and Hsp70 localization to plasma membranes in rat hearts Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1709 - H1721. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. An and B. Rodrigues Role of changes in cardiac metabolism in development of diabetic cardiomyopathy Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1489 - H1506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Hafstad, G. H. Solevag, D. L. Severson, T. S. Larsen, and E. Aasum Perfused hearts from Type 2 diabetic (db/db) mice show metabolic responsiveness to insulin Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H1763 - H1769. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Welch, J. S. Lewis, J. Kim, T. L. Sharp, C. S. Dence, R. J. Gropler, and P. Herrero Assessment of Myocardial Metabolism in Diabetic Rats Using Small-Animal PET: A Feasibility Study J. Nucl. Med., April 1, 2006; 47(4): 689 - 697. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O.-J. How, E. Aasum, D. L. Severson, W.Y. A. Chan, M. F. Essop, and T. S. Larsen Increased Myocardial Oxygen Consumption Reduces Cardiac Efficiency in Diabetic Mice Diabetes, February 1, 2006; 55(2): 466 - 473. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. M. Greer, D. P. Ware, and D. J. Lefer Myocardial infarction and heart failure in the db/db diabetic mouse Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H146 - H153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Murray, M. Panagia, D. Hauton, G. F. Gibbons, and K. Clarke Plasma Free Fatty Acids and Peroxisome Proliferator-Activated Receptor {alpha} in the Control of Myocardial Uncoupling Protein Levels Diabetes, December 1, 2005; 54(12): 3496 - 3502. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Boudina, S. Sena, B. T. O'Neill, P. Tathireddy, M. E. Young, and E. D. Abel Reduced Mitochondrial Oxidative Capacity and Increased Mitochondrial Uncoupling Impair Myocardial Energetics in Obesity Circulation, October 25, 2005; 112(17): 2686 - 2695. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O.-J. How, E. Aasum, S. Kunnathu, D. L. Severson, E. S. P. Myhre, and T. S. Larsen Influence of substrate supply on cardiac efficiency, as measured by pressure-volume analysis in ex vivo mouse hearts Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2979 - H2985. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Guan Peroxisome Proliferator-Activated Receptor Family and Its Relationship to Renal Complications of the Metabolic Syndrome J. Am. Soc. Nephrol., November 1, 2004; 15(11): 2801 - 2815. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Khairallah, F. Labarthe, B. Bouchard, G. Danialou, B. J. Petrof, and C. Des Rosiers Profiling substrate fluxes in the isolated working mouse heart using 13C-labeled substrates: focusing on the origin and fate of pyruvate and citrate carbons Am J Physiol Heart Circ Physiol, April 1, 2004; 286(4): H1461 - H1470. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. N. Carley, L. M. Semeniuk, Y. Shimoni, E. Aasum, T. S. Larsen, J. P. Berger, and D. L. Severson Treatment of type 2 diabetic db/db mice with a novel PPAR{gamma} agonist improves cardiac metabolism but not contractile function Am J Physiol Endocrinol Metab, March 1, 2004; 286(3): E449 - E455. [Abstract] [Full Text]
|
|
|
|
|
|
G. A. Francis, J.-S. Annicotte, and J. Auwerx PPAR-{alpha} effects on the heart and other vascular tissues Am J Physiol Heart Circ Physiol, June 5, 2003; 285(1): H1 - H9. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Hopkins, M. C. Sugden, M. J. Holness, R. Kozak, J. R. B. Dyck, and G. D. Lopaschuk Control of cardiac pyruvate dehydrogenase activity in peroxisome proliferator-activated receptor-{alpha} transgenic mice Am J Physiol Heart Circ Physiol, June 5, 2003; 285(1): H270 - H276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Aasum, A. D. Hafstad, D. L. Severson, and T. S. Larsen Age-Dependent Changes in Metabolism, Contractile Function, and Ischemic Sensitivity in Hearts From db/db Mice Diabetes, February 1, 2003; 52(2): 434 - 441. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Neitzel, A. N. Carley, and D. L. Severson Chylomicron and palmitate metabolism by perfused hearts from diabetic mice Am J Physiol Endocrinol Metab, February 1, 2003; 284(2): E357 - E365. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
