TY - JOUR
T1 - The role of calcium in the regulation of glucose uptake in isolated working rat heart
AU - Zechner, Christoph
AU - Beyersdorf, Friedhelm
AU - Doenst, Torsten
N1 - Funding Information:
This study was supported by a research grant to TD by the German Research Foundation (Emmy Noether-Program, No Do602/2-1).
PY - 2002
Y1 - 2002
N2 - Catecholamines or ischemia may increase myocardial glucose uptake by an increase in intracellular calcium. We tested the hypothesis that increasing or decreasing extracellular calcium supply would change glucose uptake. Hearts were perfused for 60 min at a physiological workload with Krebs-Henseleit buffer containing glucose (5 mM) and oleate (0.4 mM; bound to 1% BSA). Calcium concentration was 2.5 mM. In group A (control; n = 12), insulin (1 mU/ml) was added at 30 min. In Group B (n = 7), the calcium concentration was increased to 5.0 and 7.5 mM at 20 min and 40 min, respectively. In Group C (n = 7), verapamil was added at 20 min (0.25 μM) and 40 min (1.0 μM) to decrease calcium influx. In group D (n = 7), EDTA was added at 20 min (0.5 mM) and at 40 min (1.5 mM) to decrease the free extracellular calcium. Glucose uptake was measured by 3H2O production from [2-3H]glucose and cardiac work was measured simultaneously. Cardiac power in group B was 8.24 ± 0.60 mW at 2.5 mM calcium, 9.45 ± 0.50 mW at 5 mM calcium and 7.99 ± 0.99 mW at 7.5 mM calcium (n.s.). The addition of verapamil decreased contractile function in a dose-dependent manner (8.50 ± 0.74 vs. 3.11 ± 0.84 vs. 1.48 ± 0.39 mW, p < 0.01) suggesting that verapamil decreased cytosolic calcium concentration. A similar dose-dependent reduction in contractile performance was observed in the EDTA group (8.44 ± 0.81 vs. 7.42 ± 0.96 vs. 4.03 ± 1.32 mW, p < 0.01). Glucose uptake was 1.35 ± 0.11 μmol/min/g dry weight under control conditions. Glucose uptake increased threefold with the addition of insulin. Increasing extracellular [Ca2+] did not affect glucose uptake. Decreasing Ca2+ availability showed a trend towards a decrease in glucose uptake (n.s.), which was minor compared to the decrease in contractile function. We conclude that extracellular calcium does not regulate glucose uptake in the isolated working rat heart in the presence of glucose and fatty acids as substrates. The trend of decreased glucose uptake when calcium supply was limited may be due to dramatically reduced energy demand and not directly due to changes in calcium.
AB - Catecholamines or ischemia may increase myocardial glucose uptake by an increase in intracellular calcium. We tested the hypothesis that increasing or decreasing extracellular calcium supply would change glucose uptake. Hearts were perfused for 60 min at a physiological workload with Krebs-Henseleit buffer containing glucose (5 mM) and oleate (0.4 mM; bound to 1% BSA). Calcium concentration was 2.5 mM. In group A (control; n = 12), insulin (1 mU/ml) was added at 30 min. In Group B (n = 7), the calcium concentration was increased to 5.0 and 7.5 mM at 20 min and 40 min, respectively. In Group C (n = 7), verapamil was added at 20 min (0.25 μM) and 40 min (1.0 μM) to decrease calcium influx. In group D (n = 7), EDTA was added at 20 min (0.5 mM) and at 40 min (1.5 mM) to decrease the free extracellular calcium. Glucose uptake was measured by 3H2O production from [2-3H]glucose and cardiac work was measured simultaneously. Cardiac power in group B was 8.24 ± 0.60 mW at 2.5 mM calcium, 9.45 ± 0.50 mW at 5 mM calcium and 7.99 ± 0.99 mW at 7.5 mM calcium (n.s.). The addition of verapamil decreased contractile function in a dose-dependent manner (8.50 ± 0.74 vs. 3.11 ± 0.84 vs. 1.48 ± 0.39 mW, p < 0.01) suggesting that verapamil decreased cytosolic calcium concentration. A similar dose-dependent reduction in contractile performance was observed in the EDTA group (8.44 ± 0.81 vs. 7.42 ± 0.96 vs. 4.03 ± 1.32 mW, p < 0.01). Glucose uptake was 1.35 ± 0.11 μmol/min/g dry weight under control conditions. Glucose uptake increased threefold with the addition of insulin. Increasing extracellular [Ca2+] did not affect glucose uptake. Decreasing Ca2+ availability showed a trend towards a decrease in glucose uptake (n.s.), which was minor compared to the decrease in contractile function. We conclude that extracellular calcium does not regulate glucose uptake in the isolated working rat heart in the presence of glucose and fatty acids as substrates. The trend of decreased glucose uptake when calcium supply was limited may be due to dramatically reduced energy demand and not directly due to changes in calcium.
KW - EDTA
KW - Insulin
KW - Signal transduction
KW - Verapamil
KW - Workload
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U2 - 10.1023/A:1014897304124
DO - 10.1023/A:1014897304124
M3 - Article
C2 - 12030382
AN - SCOPUS:0036010750
SN - 0300-8177
VL - 232
SP - 75
EP - 80
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
IS - 1-2
ER -