| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom
To determine whether the
effects of fatty acids on the diabetic heart during ischemia
involve altered glycolytic ATP and proton production, we measured
energetics and intracellular pH (pHi) by using
31P NMR spectroscopy plus [2-3H]glucose
uptake in isolated rat hearts. Hearts from 7-wk streptozotocin diabetic
and control rats, perfused with buffer containing 11 mM glucose, with
or without 1.2 mM palmitate or the ketone bodies, 4 mM
-hydroxybutyrate plus 1 mM acetoacetate, were subjected to 32 min of
low-flow (0.3 ml · g wet
wt
1 · min1) ischemia,
followed by 32 min of reperfusion. In control rat hearts, neither
palmitate nor ketone bodies altered the recovery of contractile
function. Diabetic rat hearts perfused with glucose alone or with
ketone bodies, had functional recoveries 50% lower than those of the
control hearts, but palmitate restored recovery to control levels. In a
parallel group with the functional recoveries, palmitate prevented the
54% faster loss of ATP in the diabetic, glucose-perfused rat hearts
during ischemia, but had no effect on the rate of ATP depletion
in control hearts. Palmitate decreased total glucose uptake in control
rat hearts during low-flow ischemia, from 106 ± 17 to
52 ± 12 µmol/g wet wt, but did not alter the total glucose
uptake in the diabetic rat hearts, which was 42 ± 5 µmol/g wet
wt. Recovery of contractile function was unrelated to pHi
during ischemia; the glucose-perfused control and
palmitate-perfused diabetic hearts had end-ischemic
pHi values that were significantly different at 6.36 ± 0.04 and 6.60 ± 0.02, respectively, but had similar functional
recoveries, whereas the glucose-perfused diabetic hearts had
significantly lower functional recoveries, but their pHi
was 6.49 ± 0.04. We conclude that fatty acids, but not ketone bodies, protect the diabetic heart by decreasing ATP depletion, with
neither having detrimental effects on the normal rat heart during
low-flow ischemia.
31P nuclear magnetic resonance spectroscopy; substrate utilization; glucose uptake; myocardial energetics
This article has been cited by other articles:
|
|
 |
|
  M. S. Kim, F. Wang, P. Puthanveetil, G. Kewalramani, E. Hosseini-Beheshti, N. Ng, Y. Wang, U. Kumar, S. Innis, C. G. Proud, et al. Protein Kinase D Is a Key Regulator of Cardiomyocyte Lipoprotein Lipase Secretion After Diabetes Circ. Res., August 1, 2008; 103(3): 252 - 260. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. D. Evans and Y. Niu Hypolipidaemic effects of high-dose insulin therapy Br. J. Anaesth., April 1, 2008; 100(4): 429 - 433. [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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 P. Wang, S. G. Lloyd, and J. C. Chatham Impact of High Glucose/High Insulin and Dichloroacetate Treatment on Carbohydrate Oxidation and Functional Recovery After Low-Flow Ischemia and Reperfusion in the Isolated Perfused Rat Heart Circulation, April 26, 2005; 111(16): 2066 - 2072. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. G. Lloyd, P. Wang, H. Zeng, and J. C. Chatham Impact of low-flow ischemia on substrate oxidation and glycolysis in the isolated perfused rat heart Am J Physiol Heart Circ Physiol, July 1, 2004; 287(1): H351 - H362. [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. Desrois, R. J Sidell, D. Gauguier, L. M King, G. K Radda, and K. Clarke Initial steps of insulin signaling and glucose transport are defective in the type 2 diabetic rat heart Cardiovasc Res, February 1, 2004; 61(2): 288 - 296. [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]
|
|
|
|
|
|
R. J. Sidell, M. A. Cole, N. J. Draper, M. Desrois, R. E. Buckingham, and K. Clarke Thiazolidinedione Treatment Normalizes Insulin Resistance and Ischemic Injury in the Zucker Fatty Rat Heart Diabetes, April 1, 2002; 51(4): 1110 - 1117. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
