TY - JOUR
T1 - Insulin-stimulated glucose transport is dependent on golgi function in isolated working rat heart
AU - Doenst, Torsten
AU - Cedars, Ari M.
AU - Taegtmeyer, Heinrich
N1 - Funding Information:
This study was supported in part by a grant from the US Public Health Service (RO1-HL43133). Torsten Doenst was the recipient of a research fellowship from the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG).
PY - 2000
Y1 - 2000
N2 - Insulin and epinephrine stimulate glucose uptake through distinct mechanisms. We tested the hypothesis that the golgi apparatus is involved in insulin-stimulated but not epinephrine-stimulated glucose transport and phosphorylation. Methods: We perfused isolated working rat hearts with Krebs-Henseleit buffer containing [2-3H]glucose (5 mmol/l, 0.05 μCi/ml) and Na-oleate (0.4 mmol/l). In the absence or presence of the inhibitor of golgi function, brefeldin A (30 μmol/l), either insulin (1 mU/ml), epinephrine (1 μmol/l), or phenylephrine (100 μmol/l) plus propranolol (10 μmol/l, selective α-adrenergic stimulation) were added to the perfusate. Results: Cardiac power was stable in all groups (between 8.56 ± 0.61 and 10.4 ± 1.11 mW) and increased (34%) with addition of epinephrine, but not with selective α-adrenergic stimulation. Insulin, epinephrine, and selective α-receptor stimulation increased glucose transport and phosphorylation (μmol/min/g dry wt, basal: 1.19 ± 0.13, insulin: 3.89 ± 0.36, epinephrine: 3.46 ± 0.27, α-stimulation: 4.08 ± 0.40). Brefeldin A increased basal glucose transport and phosphorylation and blunted insulin-stimulated but not epinephrine-stimulated glucose transport and phosphorylation. Selective α-stimulated glucose transport and phosphorylation was also blunted by brefeldin A. Conclusions: Both insulin and α-adrenergic stimulation result in glucose transporter translocation from a pool that requires golgi function. Stimulation with epinephrine results in glucose transporter translocation from a pool that does not require golgi function. The stimulating effects of the α-adrenergic pathway on glucose transport and phosphorylation are independent of changes in cardiac performance. (C) 2000 Academic Press.
AB - Insulin and epinephrine stimulate glucose uptake through distinct mechanisms. We tested the hypothesis that the golgi apparatus is involved in insulin-stimulated but not epinephrine-stimulated glucose transport and phosphorylation. Methods: We perfused isolated working rat hearts with Krebs-Henseleit buffer containing [2-3H]glucose (5 mmol/l, 0.05 μCi/ml) and Na-oleate (0.4 mmol/l). In the absence or presence of the inhibitor of golgi function, brefeldin A (30 μmol/l), either insulin (1 mU/ml), epinephrine (1 μmol/l), or phenylephrine (100 μmol/l) plus propranolol (10 μmol/l, selective α-adrenergic stimulation) were added to the perfusate. Results: Cardiac power was stable in all groups (between 8.56 ± 0.61 and 10.4 ± 1.11 mW) and increased (34%) with addition of epinephrine, but not with selective α-adrenergic stimulation. Insulin, epinephrine, and selective α-receptor stimulation increased glucose transport and phosphorylation (μmol/min/g dry wt, basal: 1.19 ± 0.13, insulin: 3.89 ± 0.36, epinephrine: 3.46 ± 0.27, α-stimulation: 4.08 ± 0.40). Brefeldin A increased basal glucose transport and phosphorylation and blunted insulin-stimulated but not epinephrine-stimulated glucose transport and phosphorylation. Selective α-stimulated glucose transport and phosphorylation was also blunted by brefeldin A. Conclusions: Both insulin and α-adrenergic stimulation result in glucose transporter translocation from a pool that requires golgi function. Stimulation with epinephrine results in glucose transporter translocation from a pool that does not require golgi function. The stimulating effects of the α-adrenergic pathway on glucose transport and phosphorylation are independent of changes in cardiac performance. (C) 2000 Academic Press.
KW - Brefeldin A
KW - Glucose tracer
KW - Isolated working rat heart
KW - Signal transduction
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U2 - 10.1006/jmcc.2000.1181
DO - 10.1006/jmcc.2000.1181
M3 - Article
C2 - 10900174
AN - SCOPUS:0033865007
SN - 0022-2828
VL - 32
SP - 1481
EP - 1488
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
IS - 8
ER -