Phosphorylation of cardiac protein kinase B is regulated by palmitate
Phosphorylation of cardiac protein kinase B is regulated by palmitate
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DOI：
10.1152/ajpheart.00275.2002
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发表时间：
2002-09-01
影响因子：
4.8
通讯作者：
Dyck, JRB
中科院分区：
文献类型：
--
作者：
Soltys, CLM;Buchholz, L;Dyck, JRB
本研究利用离体灌注的工作大鼠心脏，研究棕榈酸调节的蛋白激酶B （PKB）磷酸化在葡萄糖代谢中的作用。在工作模式下，以11 mM葡萄糖和100 muU/ml胰岛素或100 muU/ml胰岛素和1.2 mM棕榈酸盐灌注大鼠心脏。在1.2 mM棕榈酸盐的存在下，PKB活性和磷酸化状态降低，这与糖酵解（47%）、葡萄糖氧化（84%）和葡萄糖摄取（43%）的减少有关。与骨骼肌相比，p38和ERK在胰岛素或胰岛素和棕榈酸盐的作用下，其磷酸化状态都没有发生变化。此外，1.2 mM棕榈酸盐灌注心脏后，葡萄糖氧化率的药理恢复未显示PKB磷酸化状态的增加。在培养的小鼠心肌HL-1细胞中，胰岛素显著增加PKB磷酸化，1.2 mM棕榈酸盐预处理和共处理使PKB磷酸化减弱。然而，棕榈酸盐和c -2神经酰胺处理的胰岛素刺激细胞都不能加速PKB的去磷酸化，超过单独去除胰岛素后观察到的。综上所述，这些实验表明棕榈酸盐对PKB磷酸化的控制是独立于神经酰胺的，并表明这一信号事件可能是心肌葡萄糖摄取和氧化的重要调节因子。
In this study isolated perfused working rat hearts were used to investigate the role of palmitate-regulated protein kinase B (PKB) phosphorylation on glucose metabolism. Rat hearts were perfused aerobically in working mode with 11 mM glucose and either 100 muU/ml insulin or 100 muU/ml insulin and 1.2 mM palmitate. PKB activity and phosphorylation state were reduced in the presence of 1.2 mM palmitate, which correlates with a decrease in glycolysis (47%), glucose oxidation (84%), and glucose uptake (43%). In contrast to skeletal muscle, neither p38 nor ERK underwent changes in their phosphorylation states in response to insulin or insulin and palmitate. Moreover, pharmacological restoration of glucose oxidation rates in hearts perfused with 1.2 mM palmitate demonstrated no increase in PKB phosphorylation state. In cultured mouse cardiac muscle HL-1 cells, insulin markedly increased PKB phosphorylation, which was blunted by pre- and cotreatment with 1.2 mM palmitate. However, neither palmitate nor C-2-ceramide treatment of insulin-stimulated cells was able to accelerate PKB dephosphorylation beyond that observed following the removal of insulin alone. Taken together, these experiments show the control of PKB phosphorylation by palmitate is independent of ceramide and suggest that this signaling event may be an important regulator of myocardial glucose uptake and oxidation.