Schmitz-Peiffer C, Oakes N D, Browne C L, Kraegen E W, Biden T J
Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
Am J Physiol. 1997 Nov;273(5):E915-21. doi: 10.1152/ajpendo.1997.273.5.E915.
We have recently shown that the reduction in insulin sensitivity of rats fed a high-fat diet is associated with the translocation of the novel protein kinase C epsilon (nPKC epsilon) from cytosolic to particulate fractions in red skeletal muscle and also the downregulation of cytosolic nPKC theta. Here we have further investigated the link between insulin resistance and PKC by assessing the effects of the thiazolidinedione insulin-sensitizer BRL-49653 on PKC isoenzymes in muscle. BRL-49653 increased the recovery of nPKC isoenzymes in cytosolic fractions of red muscle from fat-fed rats, reducing their apparent activation and/or downregulation, whereas PKC in control rats was unaffected. Because BRL-49653 also improves insulin-stimulated glucose uptake in fat-fed rats and reduces muscle lipid storage, especially diglyceride content, these results strengthen the association between lipid availability, nPKC activation, and skeletal muscle insulin resistance and support the hypothesis that chronic activation of nPKC isoenzymes is involved in the generation of muscle insulin resistance in fat-fed rats.
我们最近发现，喂食高脂饮食的大鼠胰岛素敏感性降低与新型蛋白激酶Cε（nPKCε）从红色骨骼肌的胞质部分易位至颗粒部分有关，同时也与胞质nPKCθ的下调有关。在此，我们通过评估噻唑烷二酮类胰岛素增敏剂BRL-49653对肌肉中PKC同工酶的影响，进一步研究了胰岛素抵抗与PKC之间的联系。BRL-49653增加了高脂喂养大鼠红色肌肉胞质部分中nPKC同工酶的恢复，降低了它们的表观激活和/或下调，而对照大鼠中的PKC则未受影响。由于BRL-49653还能改善高脂喂养大鼠胰岛素刺激的葡萄糖摄取，并减少肌肉脂质储存，尤其是甘油二酯含量，这些结果强化了脂质可用性、nPKC激活与骨骼肌胰岛素抵抗之间的关联，并支持以下假说：nPKC同工酶的慢性激活参与了高脂喂养大鼠肌肉胰岛素抵抗的产生。
