Hansen M E, Tippetts T S, Anderson M C, Holub Z E, Moulton E R, Swensen A C, Prince J T, Bikman B T
Department of Physiology and Developmental Biology, 593 WIDB, Brigham Young University, Provo, UT 84602, USA.
Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USA.
J Diabetes Res. 2014;2014:765784. doi: 10.1155/2014/765784. Epub 2014 May 18.
The purpose of this study was to determine the effect of insulin on ceramide metabolism in skeletal muscle.
Skeletal muscle cells were treated with insulin with or without palmitate for various time periods. Lipids (ceramides and TAG) were isolated and gene expression of multiple biosynthetic enzymes were quantified. Additionally, adult male mice received daily insulin injections for 14 days, followed by muscle ceramide analysis.
In muscle cells, insulin elicited an increase in ceramides comparable to palmitate alone. This is likely partly due to an insulin-induced increase in expression of multiple enzymes, particularly SPT2, which, when knocked down, prevented the increase in ceramides. In mice, 14 days of insulin injection resulted in increased soleus ceramides, but not TAG. However, insulin injections did significantly increase hepatic TAG compared with vehicle-injected animals.
This study suggests that insulin elicits an anabolic effect on sphingolipid metabolism in skeletal muscle, resulting in increased ceramide accumulation. These findings reveal a potential mechanism of the deleterious consequences of the hyperinsulinemia that accompanies insulin resistance and suggest a possible novel therapeutic target to mitigate its effects.
本研究旨在确定胰岛素对骨骼肌中神经酰胺代谢的影响。
骨骼肌细胞在有或无棕榈酸的情况下用胰岛素处理不同时间段。分离脂质（神经酰胺和甘油三酯）并对多种生物合成酶的基因表达进行定量。此外，成年雄性小鼠每天接受胰岛素注射，持续14天，随后进行肌肉神经酰胺分析。
在肌肉细胞中，胰岛素引起的神经酰胺增加与单独使用棕榈酸相当。这可能部分归因于胰岛素诱导的多种酶表达增加，特别是SPT2，当该酶被敲低时，可阻止神经酰胺增加。在小鼠中，14天的胰岛素注射导致比目鱼肌神经酰胺增加，但甘油三酯未增加。然而，与注射载体的动物相比，胰岛素注射确实显著增加了肝脏甘油三酯。
本研究表明胰岛素对骨骼肌中鞘脂代谢具有合成代谢作用，导致神经酰胺积累增加。这些发现揭示了伴随胰岛素抵抗的高胰岛素血症有害后果的潜在机制，并提出了减轻其影响的可能新治疗靶点。
