AJP - Heart and Circulatory Physiology, Vol 273, Issue 1 52-H58, Copyright © 1997 by American Physiological Society

ARTICLES

Relationship between cardiac function and substrate oxidation in hearts of diabetic rats

J. C. Chatham and J. R. Forder
Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2195, USA.

The effects of streptozotocin-induced diabetes on myocardial substrate oxidation and contractile function were investigated using 13C nuclear magnetic resonance (NMR) spectroscopy. To determine the consequences of diabetes on glucose oxidation, hearts were perfused with [1-13C]glucose (11 mM) alone as well as in the presence of insulin (to stimulate glucose transport) and dichloroacetate (to stimulate pyruvate dehydrogenase). The contribution of glucose to the tricarboxylic acid (TCA) cycle was significantly decreased in hearts from diabetic animals compared with controls, with glucose alone and with insulin; however, the addition of dichloroacetate significantly increased the contribution of glucose to the TCA cycle. Contractile function in hearts from diabetic animals was significantly depressed with glucose as the sole substrate, regardless of the presence of insulin or dichloroacetate (P < 0.0005). To determine whether diabetes had any direct effects on beta-oxidation and the TCA cycle, hearts were perfused with glucose (11 mM) plus [6-13C]hexanoate (0.5 mM) as substrates. In control hearts, with glucose plus hexanoate as substrates, hexanoate contributed 98.9 +/- 2% of the substrate entering the TCA cycle; this was significantly decreased to 90.7 +/- 0.6% in the diabetic group (P < 0.02). The addition of hexanoate to the perfusate resulted in a significant increase in peak systolic pressure in the diabetic group (P < 0.001) such that contractile function was indistinguishable from controls.

This article has been cited by other articles:

				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]

				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]

				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]

				K. Ikeda, N. Emoto, M. Matsuo, and M. Yokoyama Molecular Identification and Characterization of a Novel Nuclear Protein Whose Expression Is Up-regulated in Insulin-resistant Animals J. Biol. Chem., January 31, 2003; 278(6): 3514 - 3520. [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]

				H. Taegtmeyer, P. McNulty, and M. E. Young Adaptation and Maladaptation of the Heart in Diabetes: Part I: General Concepts Circulation, April 9, 2002; 105(14): 1727 - 1733. [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]

				J. Sakamoto, R. L. Barr, K. M. Kavanagh, and G. D. Lopaschuk Contribution of malonyl-CoA decarboxylase to the high fatty acid oxidation rates seen in the diabetic heart Am J Physiol Heart Circ Physiol, April 1, 2000; 278(4): H1196 - H1204. [Abstract] [Full Text] [PDF]

				J. C. Chatham, Z.-P. Gao, and J. R. Forder Impact of 1 wk of diabetes on the regulation of myocardial carbohydrate and fatty acid oxidation Am J Physiol Endocrinol Metab, August 1, 1999; 277(2): E342 - E351. [Abstract] [Full Text] [PDF]

				T. M. Allen and C. D. Hardin Pattern of substrate utilization in vascular smooth muscle using 13C isotopomer analysis of glutamate Am J Physiol Heart Circ Physiol, December 1, 1998; 275(6): H2227 - H2235. [Abstract] [Full Text] [PDF]

				N. Trueblood and R. Ramasamy Aldose reductase inhibition improves altered glucose metabolism of isolated diabetic rat hearts Am J Physiol Heart Circ Physiol, July 1, 1998; 275(1): H75 - H83. [Abstract] [Full Text] [PDF]