Icariin Ameliorates Palmitate-Induced Insulin Resistance Through Reducing Thioredoxin-Interacting Protein (TXNIP) and Suppressing ER Stress in C2C12 Myotubes.
Icariin Ameliorates Palmitate-Induced Insulin Resistance Through Reducing Thioredoxin-Interacting Protein (TXNIP) and Suppressing ER Stress in C2C12 Myotubes.
复制标题
DOI：
10.3389/fphar.2018.01180
复制
发表时间：
2018
影响因子：
5.6
通讯作者：
Wang C
中科院分区：
文献类型：
--
作者：
Li M;Zhang Y;Cao Y;Zhang D;Liu L;Guo Y;Wang C
硫氧还蛋白相互作用蛋白（TXNIP）和内质网（ER）应激都与骨骼肌胰岛素抵抗有关。在饮食诱导的肥胖小鼠中，已发现淫羊羊苷在正常骨骼肌C2C12细胞中模仿胰岛素的作用，并显示出抗糖尿病的特性。然而，潜在的分子机制仍有待确定。在此，我们验证了淫羊藿苷对游离脂肪酸诱导的胰岛素抵抗的保护作用归因于其调节骨骼肌细胞中TXNIP蛋白水平和内质网应激的假设。我们发现TXNIP介导饱和脂肪酸棕榈酸酯（PA）诱导的C2C12肌管胰岛素抵抗。淫羊藿苷处理可显著恢复pa -还原的蛋白酶体活性，从而降低TXNIP蛋白，抑制内质网应激，改善胰岛素敏感性。其特异性抑制剂MG132对蛋白酶体的抑制作用明显消除了淫羊藿苷对pa诱导的胰岛素抵抗的抑制作用。此外，补充MG132显著消除了淫鸡苷对内质网应激和txnip介导的下游事件（如炎症和STAT3磷酸化）的影响。这些结果清楚地表明，淫羊藿苷通过蛋白酶体依赖机制改善pa诱导的骨骼肌胰岛素抵抗，通过该机制下调TXNIP水平并抑制内质网应激。
Both thioredoxin-interacting protein (TXNIP) and endoplasmic reticulum (ER) stress are implicated in skeletal muscle insulin resistance. Icariin has been found to mimic insulin action in normal skeletal muscle C2C12 cells and display anti-diabetic properties in diet-induced obese mice. However, the underlying molecular mechanism remains to be well-established. Herein, we tested the hypothesis that the protective effects of icariin on free fatty acid-induced insulin resistance were attributed to its regulation on TXNIP protein levels and ER stress in skeletal muscle cells. We found that TXNIP mediated the saturated fatty acid palmitate (PA)-induced insulin resistance in C2C12 myotubes. Icariin treatment significantly restored PA-reduced proteasome activity resulting in reduction of TXNIP protein and suppression of ER stress, as well as improvement of insulin sensitivity. Proteasome inhibition by its specific inhibitor MG132 obviously abolished the inhibitory effect of icariin on PA-induced insulin resistance. In addition, MG132 supplementation markedly abrogated the impacts of icariin on ER stress and TXNIP-mediated downstream events such as inflammation and STAT3 phosphorylation. These results clearly indicate that icariin improves PA-induced skeletal muscle insulin resistance through a proteasome-dependent mechanism, by which icariin downregulats TXNIP levels and inhibits ER stress.
登录
查看更多内容
影响因子：
4.6
作者：
Han Yunk-Yung;Song Mi-Young;Jung Hyo-Won
通讯作者：
Jung Hyo-Won
影响因子：
29
作者：
Lerner AG;Upton JP;Praveen PV;Ghosh R;Nakagawa Y;Igbaria A;Shen S;Nguyen V;Backes BJ;Heiman M;Heintz N;Greengard P;Hui S;Tang Q;Trusina A;Oakes SA;Papa FR
通讯作者：
Papa FR
影响因子：
6.6
作者：
Diaz-Ruiz, Alberto;Guzman-Ruiz, Rocio;Malagon, Maria M.
通讯作者：
Malagon, Maria M.
影响因子：
5
作者：
Han, Yunkyung;Jung, Hyo Won;Park, Yong-Ki
通讯作者：
Park, Yong-Ki
影响因子：
3.5
作者：
Loughney, K;Hill, TR;Ferguson, K
通讯作者：
Ferguson, K