Effects of Streptozotocin-induced Diabetes and Elevation of Plasma FFA on Ceramide Metabolism in Rat Skeletal Muscle

Effects of Streptozotocin-induced Diabetes and Elevation of Plasma FFA on Ceramide Metabolism in Rat Skeletal Muscle
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DOI:
10.1055/s-0029-1238322
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发表时间:
2010-01-01
影响因子:
2.2
通讯作者:
Gorski, J.
Gorski, J.
中科院分区:
医学4区
文献类型:
--
作者:
Blachnio-Zabielska, A.;Zabielski, P.;Gorski, J.

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神经酰胺可能介导胰岛素抵抗的诱导。本研究的目的是检查链脲佐菌素糖尿病和肝素治疗对骨骼肌神经酰胺代谢的影响。实验在Wistar大鼠上进行,分为三组:1)对照组,2)用链脲佐菌素处理组,和3)用肝素处理组。对三种类型的肌肉进行测定:慢收缩氧化(比目鱼肌)、快收缩氧化糖酵解和快收缩糖酵解(分别为腓肠肌的红色和白色部分)。检测了丝氨酸棕榈酰转移酶(SPT)、中性和酸性鞘磷脂酶(nSMase和aSMase)以及中性和碱性神经酰胺酶(nCD酶和alCD酶)的活性。神经酰胺,鞘氨醇-1-磷酸的含量也进行了测量。链脲佐菌素糖尿病和肝素治疗增加了每种类型的肌肉中的SPT的活性。肝素抑制aSMase的活性,并同时诱导每块研究肌肉中nSMase的活性。链脲佐菌素降低aSMase活性在每块肌肉和增加nSMase活性在比目鱼肌和腓肠肌红段。肝素诱导,而链脲佐菌素抑制比目鱼肌和腓肠肌红段的n-CD酶的活性。肝素可增加红腓肠肌中alCD酶的活性。在比目鱼肌和白色腓肠肌中,alCD酶活性降低。链脲佐菌素显着增加神经酰胺的含量在每个肌肉研究和肝素只在比目鱼肌。它的结论是,胰岛素缺乏是伴随着骨骼肌神经酰胺代谢的改变。血浆游离脂肪酸浓度增加可能介导胰岛素缺乏的某些效应。
Ceramide is likely to mediate in induction of insulin resistance. The aim of the present study was to examine the effect of streptozotocin-diabetes and treatment with heparin on ceramide metabolism in skeletal muscles. The experiments were performed on Wistar rats divided into three groups: 1) control, 2) treated with streptozotocin, and 3) treated with heparin. Assays were carried out on three types of muscle: slow-twitch oxidative (soleus), fast-twitch oxidative-glycolytic, and fast-twitch glycolytic (red and white section of the gastrocnemius, respectively). The activity of serine palmitoyltransferase (SPT), neutral and acid sphingomyelinase (nSMase and aSMase), and neutral and alkaline ceramidase (nCDase and alCDase) was examined. The content of ceramide, sphinganine, sphingosine, and sphingosine-1-phosphate was also measured. Both streptozotocin-diabetes and treatment with heparin increased the activity of SPT in each type of muscle. Heparin inhibits the activity of aSMase and concomitantly induces the activity of nSMase in each studied muscle. Streptozotocin decreased aSMase activity in each muscle and increased nSMase activity in the soleus and red section of the gastrocnemius. Heparin induced, whereas streptozotocin inhibited the activity of n-CDase in the soleus and the red section of the gastrocnemius. Heparin increased the activity of alCDase in the red gastrocnemius. In the soleus and the white gastrocnemius the activity of alCDase decreased. Streptozotocin significantly increased the content of ceramide in each muscle studied and heparin did it only in the soleus. It is concluded that insulin deficiency is accompanied by alterations in ceramide metabolism in skeletal muscles. Increased concentration of the plasma free fatty acids may mediate certain effects of insulin deficiency.