Format

Send to

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

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.

Author information

1
Department of Pathophysiology, University of Split School of Medicine, Split, Croatia.
2
Department of Medical Chemistry and Biochemistry, University of Split School of Medicine, Split, Croatia.
3
Department of Internal Medicine, University Hospital Split, Split, Croatia.
4
Department of Anesthesiology and Intensive Care Medicine, University Hospital Split, Split, Croatia.

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.

KEYWORDS:

GM3 ganglioside; Sprague-Dawley rats; GM3神经节苷脂; Sprague-Dawley大鼠; experimental diabetes mellitus; skeletal muscle; streptozotocin; 实验性糖尿病; 链脲霉素; 骨骼肌

PMID:
28544772
DOI:
10.1111/1753-0407.12569
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center