Botanical Research Center, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA.
Diabetes. 2012 Mar;61(3):597-605. doi: 10.2337/db11-0396. Epub 2012 Feb 7.
Ectopic lipids in peripheral tissues have been implicated in attenuating insulin action in vivo. The botanical extract of Artemisia dracunculus L. (PMI 5011) improves insulin action, yet the precise mechanism is not known. We sought to determine whether the mechanism by which PMI 5011 improves insulin signaling is through regulation of lipid metabolism. After differentiation, cells were separately preincubated with free fatty acids (FFAs) and ceramide C2, and the effects on glycogen content, insulin signaling, and ceramide profiles were determined. The effect of PMI 5011 on ceramide accumulation and ceramide-induced inhibition of insulin signaling was evaluated. FFAs resulted in increased levels of total ceramides and ceramide species in L6 myotubes. Saturated FFAs and ceramide C2 inhibited insulin-stimulated phosphorylation of protein kinase B/Akt and reduced glycogen content. PMI 5011 had no effect on ceramide formation or accumulation but increased insulin sensitivity via restoration of Akt phosphorylation. PMI 5011 also attenuated the FFA-induced upregulation of a negative inhibitor of insulin signaling, i.e., protein tyrosine phosphatase 1B (PTP1B), and increased phosphorylation of PTP1B. PMI 5011 attenuates the reduction in insulin signaling induced by ceramide accumulation, but the mechanism of improved insulin signaling is independent of ceramide formation.
外周组织异位脂质被认为可减弱体内胰岛素的作用。青蒿（PMI 5011）植物提取物可改善胰岛素作用，但确切机制尚不清楚。我们试图确定 PMI 5011 改善胰岛素信号的机制是否通过调节脂质代谢。细胞分化后，分别用游离脂肪酸（FFAs）和神经酰胺 C2 预孵育，测定糖原含量、胰岛素信号和神经酰胺谱的变化。评估 PMI 5011 对神经酰胺积累和神经酰胺诱导的胰岛素信号抑制的影响。FFAs 导致 L6 肌管中总神经酰胺和神经酰胺种类的水平增加。饱和 FFAs 和神经酰胺 C2 抑制胰岛素刺激的蛋白激酶 B/Akt 磷酸化并减少糖原含量。PMI 5011 对神经酰胺形成或积累没有影响，但通过恢复 Akt 磷酸化增加胰岛素敏感性。PMI 5011 还减弱了 FFAs 诱导的胰岛素信号负抑制剂蛋白酪氨酸磷酸酶 1B（PTP1B）的上调，并增加了 PTP1B 的磷酸化。PMI 5011 可减轻神经酰胺积累引起的胰岛素信号转导减少，但改善胰岛素信号的机制与神经酰胺形成无关。
