| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Cardiovascular Research Group, University of Alberta, Edmonton, Alberta, Canada T6G 2S2
Myocardial glucose oxidation is markedly reduced in the
uncontrolled diabetic. We determined whether this was due to direct biochemical changes in the heart or whether this was due to altered circulating levels of insulin and substrates that can be seen in the
diabetic. Isolated working hearts from control or diabetic rats
(streptozotocin, 55 mg/kg iv administered 6 wk before study) were
aerobically perfused with either 5 mM [14C]glucose and
0.4 mM [3H]palmitate (low-fat/low-glucose
buffer) or 20 mM [14C]glucose and 1.2 mM
[3H]palmitate (high-fat/high-glucose buffer) ±100
µU/ml insulin. The presence of insulin increased glucose oxidation in
control hearts perfused with low-fat/low-glucose buffer from 553 ± 85 to 1,150 ± 147 nmol · g dry
wt
1 · min1
(P < 0.05). If control hearts were perfused with
high-fat/high-glucose buffer, palmitate oxidation was significantly
increased by 112% (P < 0.05), but glucose oxidation
decreased to 55% of values seen in the low-fat/low-glucose group
(P < 0.05). In diabetic hearts, glucose oxidation was very
low in hearts perfused with low-fat/low-glucose buffer (9 ± 1
nmol · g dry
wt1 · min1) and was not
altered by insulin or high-fat/high-glucose buffer. These results
suggest that neither circulating levels of substrates nor insulin was
responsible for the reduced glucose oxidation in diabetic hearts. To
determine if subcellular changes in the control of fatty acid oxidation
contribute to these changes, we measured the activity of three enzymes
involved in the control of fatty acid oxidation; AMP-activated protein
kinase (AMPK), acetyl-CoA carboxylase (ACC), and malonyl-CoA
decarboxylase (MCD). Although AMPK and ACC activity in control and
diabetic hearts was not different, MCD activity and expression in all
diabetic rat heart perfusion groups were significantly higher than that seen in corresponding control hearts. These results suggest that an
increased MCD activity contributes to the high fatty acid oxidation rates and reduced glucose oxidation rates seen in diabetic rat hearts.
adenosine 5'-monophosphate-activated protein kinase; acetyl-coenzyme A carboxylase; glucose oxidation; malonyl-coenzyme A; carnitine palmitoyltransferase 1
This article has been cited by other articles:
|
|
 |
|
  G. R. Steinberg and B. E. Kemp AMPK in Health and Disease Physiol Rev, July 1, 2009; 89(3): 1025 - 1078. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-G. Niu and R. D. Evans Metabolism of very-low-density lipoprotein and chylomicrons by streptozotocin-induced diabetic rat heart: effects of diabetes and lipoprotein preference Am J Physiol Endocrinol Metab, November 1, 2008; 295(5): E1106 - E1116. [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]
|
|
|
|
 |
|
 S. Glyn-Jones, S. Song, M. A. Black, A. R. J. Phillips, S. Y. Choong, and G. J. S. Cooper Transcriptomic analysis of the cardiac left ventricle in a rodent model of diabetic cardiomyopathy: molecular snapshot of a severe myocardial disease Physiol Genomics, February 12, 2007; 28(3): 284 - 293. [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]
|
|
|
|
|
|
J. M. O'Donnell, M. Zampino, N. M. Alpert, M. J. Fasano, D. L. Geenen, and E.D. Lewandowski Accelerated triacylglycerol turnover kinetics in hearts of diabetic rats include evidence for compartmented lipid storage Am J Physiol Endocrinol Metab, March 1, 2006; 290(3): E448 - E455. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Panagia, G. F. Gibbons, G. K. Radda, and K. Clarke PPAR-{alpha} activation required for decreased glucose uptake and increased susceptibility to injury during ischemia Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2677 - H2683. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ovide-Bordeaux and A. Grynberg Docosahexaenoic acid affects insulin deficiency- and insulin resistance-induced alterations in cardiac mitochondria Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2004; 286(3): R519 - R527. [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]
|
|
|
|
 |
|
 T. Ramanathan, K. Shirota, S. Morita, T. Nishimura, Y. Huang, X. Zheng, and S. Hunyor Left ventricular oxygen utilization efficiency is impaired in chronic streptozotocin-diabetic sheep Cardiovasc Res, September 1, 2002; 55(4): 749 - 756. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Young, P. McNulty, and H. Taegtmeyer Adaptation and Maladaptation of the Heart in Diabetes: Part II: Potential Mechanisms Circulation, April 16, 2002; 105(15): 1861 - 1870. [Full Text] [PDF]
|
|
|
|
 |
|
 F. M. Campbell, R. Kozak, A. Wagner, J. Y. Altarejos, J. R. B. Dyck, D. D. Belke, D. L. Severson, D. P. Kelly, and G. D. Lopaschuk A Role for Peroxisome Proliferator-activated Receptor alpha (PPARalpha ) in the Control of Cardiac Malonyl-CoA Levels. REDUCED FATTY ACID OXIDATION RATES AND INCREASED GLUCOSE OXIDATION RATES IN THE HEARTS OF MICE LACKING PPARalpha ARE ASSOCIATED WITH HIGHER CONCENTRATIONS OF MALONYL-CoA AND REDUCED EXPRESSION OF MALONYL-CoA DECARBOXYLASE J. Biol. Chem., February 1, 2002; 277(6): 4098 - 4103. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Young, G. W. Goodwin, J. Ying, P. Guthrie, C. R. Wilson, F. A. Laws, and H. Taegtmeyer Regulation of cardiac and skeletal muscle malonyl-CoA decarboxylase by fatty acids Am J Physiol Endocrinol Metab, March 1, 2001; 280(3): E471 - E479. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
