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L-carnitine increases glucose metabolism and mechanical function following ischaemia in diabetic rat heart
T L Broderick1, H A Quinney, G D Lopaschuk
1Cardiovascular Disease Research Group, University of Alberta, Edmonton, Canada.
Objective:
Stimulation of glucose oxidation by L-carnitine improves mechanical recovery of ischaemic hearts from non-diabetic rats perfused with high levels of fatty acids. The aim of this study was to determine whether L-carnitine also increases glucose oxidation and function in diabetic rat hearts, which have suppressed glucose metabolism.
Methods:
Isolated working hearts from six week streptozotocin diabetic and control rats were perfused with 11 mM (5-3H/U-14C)-glucose, 1.2 mM palmitate. Hearts were paced at 260 beats.min-1 during 60 min of low flow ischaemia, and were then subjected to 30 min of aerobic reperfusion. Total myocardial carnitine content in these hearts was first increased by a 60 min aerobic perfusion with 10 mM L-carnitine.
Results:
Steady state glucose oxidation rates (measured as 14CO2 production) were depressed in diabetic rat hearts compared to control hearts during the initial aerobic period. However, L-carnitine treatment dramatically increased glucose oxidation rates in the diabetic rat hearts, as well as in control hearts. Glycolysis was also lower in diabetic rat hearts compared to control hearts, although L-carnitine treatment significantly increased glycolysis only in the diabetic animals. During reperfusion, steady state rates of glucose oxidation and glycolysis returned to preischaemic values in both the control and diabetic groups. L-carnitine treatment stimulated glucose oxidation during reperfusion in control and diabetic rat hearts. Mechanical function of control hearts returned to 38(SEM 9)% of preischaemic values, whereas in L-carnitine treated hearts function returned to 90(7)% of preischaemic values. Recovery of function was 80(15)% of preischaemic in the diabetic rat hearts, and was increased to 100% of preischaemic function with L-carnitine.
Conclusions:
Carnitine improves recovery of function of ischaemic non-diabetic rats by stimulating glucose oxidation during reperfusion, whereas it may be beneficial in diabetic rat hearts by stimulating both glycolysis during ischaemia and glucose oxidation during reperfusion.