2 型糖尿病大鼠模型骨骼肌神经节苷脂 GM3 含量增加，1 型糖尿病大鼠模型则降低：糖脂代谢在糖尿病发病机制中的病理生理学意义。

Ganglioside GM3 content in skeletal muscles is increased in type 2 but decreased in type 1 diabetes rat models: Implications of glycosphingolipid metabolism in pathophysiology of diabetes.

机构信息

Department of Pathophysiology, University of Split School of Medicine, Split, Croatia.

Department of Medical Chemistry and Biochemistry, University of Split School of Medicine, Split, Croatia.

出版信息

J Diabetes. 2018 Feb;10(2):130-139. doi: 10.1111/1753-0407.12569. Epub 2017 Jun 28.

DOI:10.1111/1753-0407.12569

PMID:28544772

Abstract

BACKGROUND

Ganglioside GM3 is found in the plasma membrane, where its accumulation attenuates insulin receptor signaling. Considering the role of skeletal muscles in insulin-stimulated glucose uptake, the aim of the present study was to determine the expression of GM3 and its precursors in skeletal muscles of rat models of type 1 and type 2 diabetes mellitus (T1DM and T2DM, respectively).

METHODS

Diabetes was induced in male Sprague-Dawley rats by streptozotocin injection (55 mg/kg, i.p., for T1DM induction; 35 mg/kg, i.p., for T2DM induction), followed by feeding of rats with either a normal pellet diet (T1DM) or a high-fat diet (T2DM). Rats were killed 2 weeks after diabetes induction and samples of skeletal muscle were collected. Frozen quadriceps muscle sections were stained with a primary antibody against GM3 (Neu5Ac) and visualized using a secondary antibody coupled with Texas Red. The muscle content of ganglioside GM3 and its precursors was analyzed by high-performance thin-layer chromatography (HPTLC) followed by GM3 immunostaining.

RESULTS

Muscle GM3 content was significantly higher in T2DM compared with control rats (P < 0.001). Furthermore, levels of the GM3 precursors ceramide, glucosylceramide, and lactosylceramide were significantly higher in T2DM compared with control rats (P < 0.05), whereas ceramide content was significantly lower in T1DM rats (P < 0.05). The intensity of the GM3 band on HPTLC was significantly higher in T2DM rats (P < 0.001) and significantly lower in T1DM rats (P < 0.05) compared with control.

CONCLUSIONS

The expression patterns of GM3 ganglioside and its precursors in diabetic rats suggest that the role of glycosphingolipid metabolism may differ between T2DM and T1DM.

摘要

背景

神经节苷脂 GM3 存在于质膜中，其积累会减弱胰岛素受体信号转导。鉴于骨骼肌在胰岛素刺激的葡萄糖摄取中的作用，本研究旨在确定 1 型和 2 型糖尿病（T1DM 和 T2DM）大鼠模型骨骼肌中 GM3 及其前体的表达。

方法

链脲佐菌素（STZ）腹腔注射（55mg/kg 诱导 T1DM；35mg/kg 诱导 T2DM）诱导雄性 Sprague-Dawley 大鼠糖尿病，随后分别用普通颗粒饮食（T1DM）或高脂肪饮食（T2DM）喂养大鼠。糖尿病诱导后 2 周处死大鼠，收集骨骼肌样本。用 GM3（Neu5Ac）的一抗对冷冻四头肌切片进行染色，并用 Texas Red 偶联的二抗进行可视化。用高效薄层色谱法（HPTLC）分析神经节苷脂 GM3 及其前体的肌肉含量，然后用 GM3 免疫染色。

结果

与对照组相比，T2DM 大鼠肌肉 GM3 含量显著升高（P<0.001）。此外，T2DM 大鼠 GM3 前体神经酰胺、葡萄糖神经酰胺和乳糖神经酰胺的水平明显高于对照组（P<0.05），而 T1DM 大鼠神经酰胺含量明显低于对照组（P<0.05）。HPTLC 上 GM3 带的强度在 T2DM 大鼠中明显升高（P<0.001），在 T1DM 大鼠中明显降低（P<0.05），与对照组相比。