Insulin suppresses PDK-4 expression in skeletal muscle independently of plasma FFA

Insulin suppresses PDK-4 expression in skeletal muscle independently of plasma FFA
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DOI:
10.1152/ajpendo.00461.2003
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发表时间:
2004-07-01
影响因子:
5.1
通讯作者:
Youn, JH
Youn, JH
中科院分区:
医学2区
文献类型:
--
作者:
Lee, FN;Zhang, LH;Youn, JH

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饥饿和实验性糖尿病诱导骨骼肌中丙酮酸脱氢酶激酶(PDK)活性的稳定增加,这主要是由于PDK-4表达的选择性上调。增加的游离脂肪酸(FFA)水平已被认为是负责上调。由于这些代谢状态也具有胰岛素缺乏的特征,因此本研究旨在研究胰岛素是否对大鼠骨骼肌中PDK mRNA的表达具有显著的调节作用。在研究1中,过夜禁食的大鼠接受盐水或胰岛素输注5 h(各n=6)。在胰岛素输注期间,将血糖钳夹在基础水平(正常血糖高胰岛素钳夹)。第三组(n=6)在钳夹过程中接受Intraperoid输注,以防止血浆FFA下降。腓肠肌中的PDK-2 mRNA水平不被胰岛素或FFA改变(即,内毒素输注)。而胰岛素使PDK-4 mRNA水平下降72%(P
Starvation and experimental diabetes induce a stable increase in pyruvate dehydrogenase kinase (PDK) activity in skeletal muscle, which is largely due to a selective upregulation of PDK-4 expression. Increased free fatty acid (FFA) level has been suggested to be responsible for the upregulation. Because these metabolic states are also characterized by insulin deficiency, the present study was designed to examine whether insulin has a significant effect to regulate PDK mRNA expression in rat skeletal muscle. In study 1, overnight-fasted rats received an infusion of saline or insulin for 5 h (n=6 each). During the insulin infusion, plasma glucose was clamped at basal levels (euglycemic hyperinsulinemic clamp). A third group (n=6) received Intralipid infusion during the clamp to prevent a fall in plasma FFA. PDK-2 mRNA level in gastrocnemius muscle was not altered by insulin or FFA (i.e., Intralipid infusion). In contrast, PDK-4 mRNA level was decreased 72% by insulin (P