scholarly journals Preferential inhibition of lactate oxidation relative to glucose oxidation in the rat heart following diabetes

1999 ◽  
Vol 43 (1) ◽  
pp. 96-106 ◽  
Author(s):  
J Chatham
2010 ◽  
Vol 299 (4) ◽  
pp. H1135-H1145 ◽  
Author(s):  
Jagdip S. Jaswal ◽  
Chad R. Lund ◽  
Wendy Keung ◽  
Donna L. Beker ◽  
Ivan M. Rebeyka ◽  
...  

Isoproterenol increases phosphorylation of LKB, 5′-AMP-activated protein kinase (AMPK), and acetyl-CoA carboxylase (ACC), enzymes involved in regulating fatty acid oxidation. However, inotropic stimulation selectively increases glucose oxidation in adult hearts. In the neonatal heart, fatty acid oxidation becomes a major energy source, while glucose oxidation remains low. This study tested the hypothesis that increased energy demand imposed by isoproterenol originates from fatty acid oxidation, secondary to increased LKB, AMPK, and ACC phosphorylation. Isolated working hearts from 7-day-old rabbits were perfused with Krebs solution (0.4 mM palmitate, 11 mM glucose, 0.5 mM lactate, and 100 mU/l insulin) with or without isoproterenol (300 nM). Isoproterenol increased myocardial O2 consumption (in J·g dry wt−1·min−1; 11.0 ± 1.4, n = 8 vs. 7.5 ± 0.8, n = 6, P < 0.05), and the phosphorylation of LKB (in arbitrary density units; 0.87 ± 0.09, n = 6 vs. 0.59 ± 0.08, n = 6, P < 0.05), AMPK (0.82 ± 0.08, n = 6 vs. 0.51 ± 0.06, n = 6, P < 0.05), and ACC-β (1.47 ± 0.14, n = 6 vs. 0.97 ± 0.07, n = 6, P < 0.05), with a concomitant decrease in malonyl-CoA levels (in nmol/g dry wt; 0.9 ± 0.9, n = 8 vs. 7.5 ± 1.3, n = 8, P < 0.05) and increase in palmitate oxidation (in nmol·g dry wt−1·min−1; 272 ± 45, n = 8 vs. 114 ± 9, n = 6, P < 0.05). Glucose and lactate oxidation were increased (in nmol·g dry wt−1·min−1; 253 ± 75, n = 8 vs. 63 ± 15, n = 9, P < 0.05 and 246 ± 43, n = 8 vs. 82 ± 11, n = 6, P < 0.05, respectively), independent of alterations in pyruvate dehydrogenase phosphorylation, but occurred secondary to a decrease in acetyl-CoA content and acetyl-CoA-to-free CoA ratio. As acetyl-CoA levels decrease in response to isoproterenol, despite an acceleration of the rates of palmitate and carbohydrate oxidation, these data suggest net rates of acetyl-CoA utilization exceed the net rates of acetyl-CoA generation.


1992 ◽  
Vol 72 (3) ◽  
pp. 1149-1155 ◽  
Author(s):  
B. P. deBoisblanc ◽  
K. Meszaros ◽  
A. Burns ◽  
G. J. Bagby ◽  
S. Nelson ◽  
...  

We investigated the effect of dichloroacetate (DCA) on tension generation and carbohydrate metabolism of the rat diaphragm in vitro. Isolated diaphragms were placed in individual organ chambers and were hooked to force-displacement transducers. Net lactate production and glucose and lactate oxidation were measured in vitro. Diaphragmatic fatigue was precipitated by in vivo endotoxemic shock, by in vitro hypoxia, or by in vitro repetitive tetanic stimulation. In diaphragms isolated from endotoxemic rats, DCA increased tension generation by 30 and 20% at stimulation frequencies of 20 and 100 Hz, respectively. Associated with changes in mechanical performance, DCA reduced net lactate production by 53% after 60 min of incubation and increased glucose oxidation 54% but had no effect on lactate oxidation. During in vitro hypoxia, DCA reduced net diaphragmatic lactate production by 30% and increased glucose oxidation by 45% but did not attenuate hypoxic fatigue. DCA had no effect on tension generation during repetitive tetanic stimulation. We conclude that DCA improves in vitro diaphragmatic fatigue due to endotoxicosis but not due to hypoxia or repetitive stimulation.


1962 ◽  
Vol 203 (5) ◽  
pp. 839-843 ◽  
Author(s):  
Lionel H. Opie ◽  
Joseph C. Shipp ◽  
John R. Evans ◽  
Bernard Leboeuf

A closed perfusion system was designed to study C14O2 formation during uptake of glucose-U-C14 by the isolated, beating rat heart. An initial period of 5 min of preperfusion with oxygenated buffer allowed stabilization of the heart before 30 min of perfusion in the closed recirculation system. Oxygenation was adequate as judged by cardiac rate and force, the pattern of glucose metabolism, the rate of glycogenolysis, and the perfusate oxygen content. Glucose uptake increased sharply with increasing perfusate glucose concentrations over the range 1.25– 5 mm glucose, with a lesser rise in the 5–10 mm range and very little rise from 10–40 mm. Glucose oxidation, which accounted for 60% of the glucose uptake at 1.25 mm glucose concentration, reached a maximal rate at 5–10 mm. This maximal rate accounted for only 24% of the glucose uptake at 40 mm, indicating the increasing importance of nonoxidative fates of glucose with increasing glucose uptake. Lactate and net glycogen formation, and incorporation of glucose carbon into glycogen, were least at lowest glucose concentrations and increased irregularly as the glucose concentration rose. Uptake and oxidation of fructose-U-C14 (5 mm) was much less than that of glucose.


1980 ◽  
Vol 238 (5) ◽  
pp. E480-E486 ◽  
Author(s):  
M. E. Tischler ◽  
A. L. Goldberg

Both left and right atria from fasted rats produced significant amounts of 14CO2 during incubation with U-14C-labeled leucine, isoleucine, valine, alanine, glutamate, glutamine, aspartate, asparagine, proline, threonine, or lysine. This pattern of amino acid metabolism resembles that of skeletal muscle. Production of 14CO2 from [1-14C]leucine was 2.5-fold greater in atria from fasted than from fed rats and was due to greater alpha-ketoisocaproic dehydrogenase activity in the tissue from fasted animals. At normal plasma concentrations, leucine reduced the oxidation of glucose and lactate in atria from fasted but not from fed rats by inhibiting pyruvate oxidation and without altering the rate of glycolysis. Leucine also reduced glucose oxidation when added in the presence of ketone bodies or other amino acids and stimulated the release of lactate into the medium. Although the leucine skeleton can be completely oxidized to CO2 and thus can serve as an alternative fuel in fasting in place of glucose, oxidation of leucine (like glucose or lactate oxidation) accounts only for a very small fraction of the total oxygen consumption of the resting atria.


1984 ◽  
Vol 62 (5) ◽  
pp. 581-588 ◽  
Author(s):  
I. Bihler ◽  
T. K. Ho ◽  
P. C. Sawh

A procedure for the isolation of myocytes from adult rat hearts is described. It is based on successive treatments with Ca2+-free medium, disaggregating enzymes (collagenase and hyaluronidase) and mechanical agitation. Several recent isolation methods were compared and their best features were combined, together with some original modifications. A good yield of high purity myocytes with excellent morphological and functional integrity was obtained. The cells are tolerant to physiological concentrations of Ca2+. Cellular levels of ATP, Na+ and K+ are close to those in intact hearts and glucose oxidation rates and succinate exclusion are also close to normal. These characteristics are maintained for periods over 1 h.


1977 ◽  
Vol 93 (1) ◽  
pp. 31-39 ◽  
Author(s):  
Miriam D. Rosenthal ◽  
Joseph B. Warshaw

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