Given M B, Jie O, Zhao X, GIles T D, Greenberg S S
Department of Medicine, Alcohol Research Center, Louisiana State University Medical Center, New Orleans 70112, USA.
Proc Soc Exp Biol Med. 1998 Sep;218(4):382-9. doi: 10.3181/00379727-218-44308.
This study examined the changes in PKC isozyme activity, content, and cellular distribution in rat gastrocnemius and soleus muscles prior to any evidence of neural degeneration or impaired skeletal muscle function, during the onset of streptozocin-induced (STZ) and genetic diabetes mellitus (DM). PKC activity was increased more in the particulate than in the soluble fractions of the soleus and gastrocnemius muscles obtained from rats treated with STZ and the gastrocnemius muscle obtained from BB-Wor diabetic rats (D rats). The predominant constitutive PKC isozymes in the skeletal muscles obtained from the STZ-treated and D rats were PKCalpha >> PKCepsilon > PKCdelta as determined by Western immunoblot assay. The content of each PKC isozyme did not differ between the soleus and gastrocnemius muscles of the control Sprague-Dawley rats for the STZ-treated rats and the BB Wor diabetic resistant (DR) rats. Moreover, the PKC isozyme content did not differ in the soluble fraction of D or STZ rats when compared to their corresponding control animals. PKCdelta increased more than PKCalpha or PKCepsilon in the particulate fraction of gastrocnemius and soleus muscles when obtained from either D or STZ rats. Since similar changes in skeletal muscle PKC isozyme profiles occurred independent of the duration of the diabetes and thereby the degree of nerve degeneration, insulin resistance, and the model of DM tested, we conclude that changes in skeletal muscle PKC precede the skeletal muscle myopathy of DM.
本研究检测了链脲佐菌素诱导（STZ）和遗传性糖尿病（DM）发病期间，大鼠腓肠肌和比目鱼肌在出现任何神经变性或骨骼肌功能受损迹象之前，蛋白激酶C（PKC）同工酶活性、含量及细胞分布的变化。从接受STZ治疗的大鼠以及BB-Wor糖尿病大鼠（D大鼠）获取的腓肠肌中，PKC活性在微粒体部分的增加幅度大于可溶性部分，且在接受STZ治疗的大鼠获取的比目鱼肌及腓肠肌中也是如此。通过蛋白质免疫印迹法测定，从接受STZ治疗的大鼠和D大鼠获取的骨骼肌中，主要的组成型PKC同工酶为PKCalpha >> PKCepsilon > PKCdelta。对于接受STZ治疗的大鼠和BB Wor糖尿病抵抗（DR）大鼠，对照Sprague-Dawley大鼠的比目鱼肌和腓肠肌中各PKC同工酶的含量并无差异。此外，与相应的对照动物相比，D大鼠或STZ大鼠的可溶性部分中PKC同工酶含量也无差异。从D大鼠或STZ大鼠获取的腓肠肌和比目鱼肌微粒体部分中，PKCdelta的增加幅度大于PKCalpha或PKCepsilon。由于骨骼肌PKC同工酶谱的类似变化独立于糖尿病持续时间，因此也独立于神经变性程度、胰岛素抵抗及所测试的DM模型，我们得出结论，骨骼肌PKC的变化先于DM的骨骼肌肌病。
