© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Preferential inhibition of lactate oxidation relative to glucose oxidation in the rat heart following diabetes
aDivision of NMR Research, Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
bDepartment of Kinesiology, University of Waterloo, Waterloo Ontario, N2L 3G1, Canada
* Corresponding author. Tel.: +1-410-955-7491; fax: +1-410-955-7923 jchatham{at}mri.jhu.edu
Objective: Alterations in myocardial metabolism occur early after the onset of diabetes suggesting that they may play a role in the development of cardiac dysfunction. Inhibition of myocardial pyruvate dehydrogenase (PDH), glucose transport and glycolysis have all been reported following diabetes. In vivo lactate is also a potential source of energy for the heart and its oxidation should not be affected by changes in glucose transport and glycolysis. Therefore, the objective of this study, was to test the hypothesis that following diabetes the inhibition of glucose oxidation would be greater than the inhibition of lactate oxidation. Methods: Hearts from control and one-week-old diabetic rats were perfused with [1-13C]glucose (11 mmol/l) alone, [1-13C]glucose plus lactate (0.5 mmol/l) or glucose plus [3-13C]lactate (0.5 or 1.0 mmol/l) as substrates. Glucose and lactate oxidation rates were determined by combining 13C-NMR glutamate isotopomer analysis of tissue extracts with measurements of oxygen consumption. Results: In diabetic hearts perfused with glucose alone, glucose oxidation was decreased compared to controls (0.31±0.08 vs. 0.71±0.11 µmoles/min/g wet weight; p<0.05). Surprisingly, in hearts perfused with glucose plus 0.5 mmol/l lactate, there was no difference in glucose oxidation between control and diabetic groups (0.20±0.05 vs. 0.16±0.04 µmoles/min/g wet weight respectively). However, under these conditions lactate oxidation was markedly reduced in the diabetic group (0.89±0.18 vs. 0.24±0.05 µmoles/min/g wet weight; p<0.05). At 1.0 mmol/l lactate oxidation was still significantly depressed in the diabetic group. Conclusion: There was a greater decrease in lactate oxidation relative to glucose oxidation in hearts from diabetic animals. These results demonstrate that diabetes leads to a specific inhibition of lactate oxidation independent of its effects on pyruvate dehydrogenase.
KEYWORDS Cardiomyopathy; Diabetes; Energy metabolism; NMR; Ventricular function
![]()
CiteULike
Connotea
Del.icio.us What's this?
This article has been cited by other articles:
![]() |
J. Yang, Y. Park, H. Zhang, X. Xu, G. A. Laine, K. C. Dellsperger, and C. Zhang Feed-forward signaling of TNF-{alpha} and NF-{kappa}B via IKK-{beta} pathway contributes to insulin resistance and coronary arteriolar dysfunction in type 2 diabetic mice Am J Physiol Heart Circ Physiol, June 1, 2009; 296(6): H1850 - H1858. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Palanivel, V. Vu, M. Park, X. Fang, and G. Sweeney Differential impact of adipokines derived from primary adipocytes of wild-type versus streptozotocin-induced diabetic rats on glucose and fatty acid metabolism in cardiomyocytes J. Endocrinol., December 1, 2008; 199(3): 389 - 397. [Abstract] [Full Text] [PDF] |
||||
![]() |
J.-Y. Deng, J.-P. Huang, L.-S. Lu, and L.-M. Hung Impairment of cardiac insulin signaling and myocardial contractile performance in high-cholesterol/fructose-fed rats Am J Physiol Heart Circ Physiol, August 1, 2007; 293(2): H978 - H987. [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] |
||||
![]() |
P. Herrero, Z. Kisrieva-Ware, C. S. Dence, B. Patterson, A. R. Coggan, D.-H. Han, Y. Ishii, P. Eisenbeis, and R. J. Gropler PET Measurements of Myocardial Glucose Metabolism with 1-11C-Glucose and Kinetic Modeling J. Nucl. Med., June 1, 2007; 48(6): 955 - 964. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Enoki, Y. Yoshida, J. Lally, H. Hatta, and A. Bonen Testosterone increases lactate transport, monocarboxylate transporter (MCT) 1 and MCT4 in rat skeletal muscle J. Physiol., November 15, 2006; 577(1): 433 - 443. [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] |
||||
![]() |
L. Zhou, M. E. Cabrera, I. C. Okere, N. Sharma, and W. C. Stanley Regulation of myocardial substrate metabolism during increased energy expenditure: insights from computational studies Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H1036 - H1046. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Wang, S. G. Lloyd, H. Zeng, A. Bonen, and J. C. Chatham Impact of altered substrate utilization on cardiac function in isolated hearts from Zucker diabetic fatty rats Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2102 - H2110. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Burelle, R. B. Wambolt, M. Grist, H. L. Parsons, J. C. F. Chow, C. Antler, A. Bonen, A. Keller, G. A. Dunaway, K. M. Popov, et al. Regular exercise is associated with a protective metabolic phenotype in the rat heart Am J Physiol Heart Circ Physiol, September 1, 2004; 287(3): H1055 - H1063. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z. Y. Fang, J. B. Prins, and T. H. Marwick Diabetic Cardiomyopathy: Evidence, Mechanisms, and Therapeutic Implications Endocr. Rev., August 1, 2004; 25(4): 543 - 567. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Wang and J. C. Chatham Onset of diabetes in Zucker diabetic fatty (ZDF) rats leads to improved recovery of function after ischemia in the isolated perfused heart Am J Physiol Endocrinol Metab, May 1, 2004; 286(5): E725 - E736. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Scheuermann-Freestone, P. L. Madsen, D. Manners, A. M. Blamire, R. E. Buckingham, P. Styles, G. K. Radda, S. Neubauer, and K. Clarke Abnormal Cardiac and Skeletal Muscle Energy Metabolism in Patients With Type 2 Diabetes Circulation, June 24, 2003; 107(24): 3040 - 3046. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Lloyd, C. Brocks, and J. C. Chatham Differential modulation of glucose, lactate, and pyruvate oxidation by insulin and dichloroacetate in the rat heart Am J Physiol Heart Circ Physiol, June 5, 2003; 285(1): H163 - H172. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Enoki, Y. Yoshida, H. Hatta, and A. Bonen Exercise training alleviates MCT1 and MCT4 reductions in heart and skeletal muscles of STZ-induced diabetic rats J Appl Physiol, June 1, 2003; 94(6): 2433 - 2438. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. C Chatham and A.-M. L Seymour Cardiac carbohydrate metabolism in Zucker diabetic fatty rats Cardiovasc Res, July 1, 2002; 55(1): 104 - 112. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. C. Chatham, C. Des Rosiers, and J. R. Forder Evidence of separate pathways for lactate uptake and release by the perfused rat heart Am J Physiol Endocrinol Metab, October 1, 2001; 281(4): E794 - E802. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. M. King, R. J. Sidell, J. R. Wilding, G. K. Radda, and K. Clarke Free fatty acids, but not ketone bodies, protect diabetic rat hearts during low-flow ischemia Am J Physiol Heart Circ Physiol, March 1, 2001; 280(3): H1173 - H1181. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. D. Belke, T. S. Larsen, E. M. Gibbs, and D. L. Severson Altered metabolism causes cardiac dysfunction in perfused hearts from diabetic (db/db) mice Am J Physiol Endocrinol Metab, November 1, 2000; 279(5): E1104 - E1113. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Vincent, B. Comte, M. Poirier, and C. D. Rosiers Citrate release by perfused rat hearts: a window on mitochondrial cataplerosis Am J Physiol Endocrinol Metab, May 1, 2000; 278(5): E846 - E856. [Abstract] [Full Text] [PDF] |
||||








