Obanda Diana N, Ribnicky David, Yu Yongmei, Stephens Jacqueline, Cefalu William T
Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA.
Department of Plant Biology, Rutgers University, New Brunswick, NJ 08901, USA.
Sci Rep. 2016 Feb 26;6:22222. doi: 10.1038/srep22222.
The leaf extract of Urtica dioica L. (UT) has been reported to improve glucose homeostasis in vivo, but definitive studies on efficacy and mechanism of action are lacking. We investigated the effects of UT on obesity- induced insulin resistance in skeletal muscle. Male C57BL/6J mice were divided into three groups: low-fat diet (LFD), high-fat diet (HFD) and HFD supplemented with UT. Body weight, body composition, plasma glucose and plasma insulin were monitored. Skeletal muscle (gastrocnemius) was analyzed for insulin sensitivity, ceramide accumulation and the post translational modification and activity of protein phosphatase 2A (PP2A). PP2A is activated by ceramides and dephosphorylates Akt. C2C12 myotubes exposed to excess free fatty acids with or without UT were also evaluated for insulin signaling and modulation of PP2A. The HFD induced insulin resistance, increased fasting plasma glucose, enhanced ceramide accumulation and PP2A activity in skeletal muscle. Supplementation with UT improved plasma glucose homeostasis and enhanced skeletal muscle insulin sensitivity without affecting body weight and body composition. In myotubes, UT attenuated the ability of FFAs to induce insulin resistance and PP2A hyperactivity without affecting ceramide accumulation and PP2A expression. UT decreased PP2A activity through posttranslational modification that was accompanied by a reduction in Akt dephosphorylation.
据报道，荨麻叶提取物（UT）可改善体内葡萄糖稳态，但缺乏关于其功效和作用机制的确切研究。我们研究了UT对肥胖诱导的骨骼肌胰岛素抵抗的影响。将雄性C57BL/6J小鼠分为三组：低脂饮食（LFD）组、高脂饮食（HFD）组和补充UT的HFD组。监测体重、身体组成、血糖和胰岛素水平。分析骨骼肌（腓肠肌）的胰岛素敏感性、神经酰胺积累以及蛋白磷酸酶2A（PP2A）的翻译后修饰和活性。PP2A被神经酰胺激活并使Akt去磷酸化。还评估了在有或无UT的情况下，暴露于过量游离脂肪酸的C2C12肌管的胰岛素信号传导和PP2A调节情况。HFD诱导胰岛素抵抗，增加空腹血糖，增强骨骼肌中的神经酰胺积累和PP2A活性。补充UT可改善血糖稳态并增强骨骼肌胰岛素敏感性，而不影响体重和身体组成。在肌管中，UT减弱了游离脂肪酸诱导胰岛素抵抗和PP2A过度活跃的能力，而不影响神经酰胺积累和PP2A表达。UT通过翻译后修饰降低PP2A活性，同时伴随着Akt去磷酸化的减少。
