Dimopoulos Nikolaos, Watson Maria, Green Charlotte, Hundal Harinder S
Division of Molecular Physiology, Sir James Black Centre, College of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom.
FEBS Lett. 2007 Oct 2;581(24):4743-8. doi: 10.1016/j.febslet.2007.08.072. Epub 2007 Sep 6.
Peroxisome proliferator-activated receptor-delta (PPARdelta) activation enhances skeletal muscle fatty acid oxidation and improves whole body glucose homeostasis and insulin sensitivity. Recently, GW501516, a selective PPARdelta agonist, was reported to increase glucose uptake in human skeletal myotubes by an AMPK-dependent mechanism that may contribute to the improved glucose tolerance. Here, we demonstrate that whilst GW501516 increases expression of PGC-1alpha and CPT-1 and stimulates fatty-acid oxidation in L6 myotubes, it fails to enhance insulin sensitivity, AMPK activity or glucose uptake and storage. Our findings exclude sarcolemmal glucose transport as a potential target for the therapeutic action of PPARdelta agonists in skeletal muscle.
过氧化物酶体增殖物激活受体δ（PPARδ）的激活可增强骨骼肌脂肪酸氧化，并改善全身葡萄糖稳态和胰岛素敏感性。最近，有报道称GW501516，一种选择性PPARδ激动剂，通过一种可能有助于改善葡萄糖耐量的AMPK依赖性机制增加人骨骼肌肌管中的葡萄糖摄取。在此，我们证明，虽然GW501516增加了PGC-1α和CPT-1的表达并刺激L6肌管中的脂肪酸氧化，但它未能增强胰岛素敏感性、AMPK活性或葡萄糖摄取及储存。我们的研究结果排除了肌膜葡萄糖转运作为PPARδ激动剂在骨骼肌中治疗作用的潜在靶点。
