链脲佐菌素诱导的糖尿病对大鼠骨骼肌中鞘磷脂信号通路功能的影响。

Effect of streptozotocin-diabetes on the functioning of the sphingomyelin-signalling pathway in skeletal muscles of the rat.

作者信息

Górska M, Dobrzyń A, Zendzian-Piotrowska M, Górski J

机构信息

Department of Gerontology, Medical University of Białystok, Białystok, Poland.

出版信息

Horm Metab Res. 2004 Jan;36(1):14-21. doi: 10.1055/s-2004-814197.

DOI:10.1055/s-2004-814197

PMID:14983401

Abstract

AIMS/HYPOTHESIS: Ceramide is the main second messenger in the sphingomyelin-transmembrane signalling pathway. The compound is likely to play a role in the induction of insulin resistance. The aim of the present study was to examine the effect of streptozotocin diabetes on the content and composition of ceramides and sphingomyelins and the activity of neutral Mg (2+)-dependent sphingomyelinase and acid sphingomyelinase in different types of skeletal muscle of the rat.

METHODS

The experiments were carried out on two groups of male Wistar rats weighing 250-280 g: controls and those treated with streptozotocin at a dose of 60 mg/kg. Determinations were performed on three types of skeletal muscle: the slow-twitch oxidative (soleus), fast-twitch oxidative-glycolytic (red section of the gastrocnemius) and fast-twitch glycolytic (white section of the same muscle). The content and composition of ceramide- and sphingomyelin-fatty acids were determined using gas-liquid chromatography. The activity of the enzymes was measured using N-[(14)CH (3)]-sphingomyelin as the substrate.

RESULTS

Twelve different ceramides and sphingomyelins were identified and quantified in each muscle with regard to the fatty acid residue. The ratio of total content of ceramide-saturated fatty acids to the total content of ceramide-unsaturated fatty acids was more than two. In the case of sphingomyelin, the ratio was similar to ceramide in the soleus and much higher in both sections of the gastrocnemius. Treatment with streptozotocin increased the total content of ceramide-fatty acids by 78% (p < 0.001) in the soleus, 27.5% (p < 0.01) in the red and 36.9% (p < 0.001) in the white section of the gastrocnemius. Concomitantly, the total content of sphingomyelin-fatty acids decreased by 43.8%, 31.2%, 24.8% (p < 0.001 in each case) in the respective muscles. The activity of neutral Mg (2+)-dependent sphingomyelinase was elevated by 69.5%, 105.9% and 62.3% in the soleus and red and white gastrocnemius, respectively (p < 0.001 for each muscle). The activity of acid sphingomyelinase was stable in the soleus and white gastrocnemius and decreased by 15.7% (p < 0.01) in the red gastrocnemius.

CONCLUSION/INTERPRETATION: The results obtained show that insulin deficiency results in elevation in the content of ceramide in skeletal muscles. This indicates that the hormone is involved in regulation of the activity of the sphingomyelin-signalling pathway in the muscles.

摘要

目的/假设：神经酰胺是鞘磷脂跨膜信号通路中的主要第二信使。该化合物可能在胰岛素抵抗的诱导中起作用。本研究的目的是研究链脲佐菌素诱导的糖尿病对大鼠不同类型骨骼肌中神经酰胺和鞘磷脂的含量及组成，以及中性镁离子依赖性鞘磷脂酶和酸性鞘磷脂酶活性的影响。

方法

实验在两组体重250 - 280 g的雄性Wistar大鼠上进行：对照组和接受60 mg/kg链脲佐菌素治疗的大鼠。对三种类型的骨骼肌进行测定：慢肌氧化型（比目鱼肌）、快肌氧化 - 糖酵解型（腓肠肌红色部分）和快肌糖酵解型（同一肌肉的白色部分）。使用气液色谱法测定神经酰胺和鞘磷脂脂肪酸的含量及组成。以N-[(14)CH (3)]-鞘磷脂为底物测量酶的活性。

结果

就脂肪酸残基而言，在每块肌肉中鉴定并定量了12种不同的神经酰胺和鞘磷脂。神经酰胺饱和脂肪酸总含量与神经酰胺不饱和脂肪酸总含量的比值大于2。对于鞘磷脂，比目鱼肌中的该比值与神经酰胺相似，而在腓肠肌的两个部分中则高得多。链脲佐菌素治疗使比目鱼肌中神经酰胺脂肪酸的总含量增加了78%（p < 0.001），腓肠肌红色部分增加了27.5%（p < 0.01），白色部分增加了36.9%（p < 0.001）。与此同时，各肌肉中鞘磷脂脂肪酸的总含量分别下降了43.8%、31.2%、24.8%（每种情况p < 0.001）。中性镁离子依赖性鞘磷脂酶的活性在比目鱼肌、腓肠肌红色和白色部分分别升高了69.5%、105.9%和62.3%（每块肌肉p < 0.001）。酸性鞘磷脂酶的活性在比目鱼肌和腓肠肌白色部分稳定，在腓肠肌红色部分下降了15.7%（p < 0.01）。

结论/解读：所得结果表明胰岛素缺乏导致骨骼肌中神经酰胺含量升高。这表明该激素参与肌肉中鞘磷脂信号通路活性的调节。