Open AccessGanglioside GM3 content in skeletal muscles is increased in type 2 but decreased in type 1 diabetes rat models: I mplications of glycosphingolipid metabolism in pathophysiology of diabetes
Author(s) -
Bozic Josko,
Markotic Anita,
CikesCulic Vedrana,
Novak Anela,
Borovac Josip A.,
Vucemilovic Hrvoje,
Trgo Gorana,
Ticinovic Kurir Tina
Publication year - 2018
Publication title -
journal of diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.949
H-Index - 43
eISSN - 1753-0407
pISSN - 1753-0393
DOI - 10.1111/1753-0407.12569
Subject(s) - medicine , endocrinology , lactosylceramide , skeletal muscle , ganglioside , glycosphingolipid , streptozotocin , type 1 diabetes , diabetes mellitus , ceramide , immunostaining , insulin , type 2 diabetes , chemistry , immunohistochemistry , biochemistry , immunology , apoptosis , glycolipid
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 S prague‐ D awley 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 T exas R ed. 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 .