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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
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