Park Jae Eun, Han Ji Sook
Department of Food Science and Nutrition, Pusan National University, 2, Busandaehak-ro 63beon-gil, Geumjeong-gu, Busan, 46241, Republic of Korea.
Toxicol Res (Camb). 2024 Dec 5;13(6):tfae197. doi: 10.1093/toxres/tfae197. eCollection 2024 Dec.
Increased plasma-free fatty acid (FFA) induced by obesity can trigger insulin resistance and it is a significantly dangerous constituent in the progression of diabetes. Although ferulic acid has various physiological functions, no studies have examined ferulic acid's effects on insulin-resistant muscle cells. This study investigated the effect of ferulic acid on improving palmitic acid-induced insulin resistance in L6 skeletal muscle cells.
Palmitic acid induces insulin resistance by inhibiting the phosphorylation of IRS-1 and stimulating the phosphorylation of IRS-1 in diabetes. Thus, palmitic acid (0.75 mM) was used as an insulin resistance inducer and ferulic acid was treated at various concentrations (2, 5, 10, and 20 uM) in L6 skeletal muscle cells.
Palmitic acid significantly reduced the cell viability of L6 skeletal muscle cells, whereas ferulic acid treatment significantly increased cell viability in a concentration-dependent manner. Palmitic acid significantly reduced glucose uptake due to insulin resistance in the muscle cells; however, ferulic acid treatment remarkably increased glucose uptake. Ferulic acid promoted the phosphorylation of IRS-1 that palmitic acid inhibited, while also suppressing the palmitic acid-induced phosphorylation of IRS-1. Ferulic acid activated PI3K and then stimulated the phosphorylation of Akt, which increased PM-GLUT4 expression, thereby stimulating glucose uptake into insulin-resistant muscle cells. Ferulic acid also increased glycogen synthesis by phosphorylating GSK3β via the Akt pathway. Additionally, ferulic acid significantly promoted phosphorylation of AMPK, enhancing PM-GLUT4 levels and glucose uptake.
These results suggest that ferulic acid may improve palmitate-induced insulin resistance by regulating IRS-1/ Akt and the AMPK pathway in L6 skeletal muscle cells.
肥胖导致的血浆游离脂肪酸（FFA）增加可引发胰岛素抵抗，且是糖尿病进展中一种极具危险性的成分。尽管阿魏酸具有多种生理功能，但尚无研究探讨其对胰岛素抵抗肌肉细胞的影响。本研究调查了阿魏酸对改善棕榈酸诱导的L6骨骼肌细胞胰岛素抵抗的作用。
棕榈酸通过抑制IRS-1的磷酸化并在糖尿病中刺激IRS-1的磷酸化来诱导胰岛素抵抗。因此，将棕榈酸（0.75 mM）用作胰岛素抵抗诱导剂，并在L6骨骼肌细胞中用不同浓度（2、5、10和20 μM）的阿魏酸进行处理。
棕榈酸显著降低了L6骨骼肌细胞的活力，而阿魏酸处理则以浓度依赖的方式显著提高了细胞活力。棕榈酸因肌肉细胞中的胰岛素抵抗而显著降低葡萄糖摄取；然而，阿魏酸处理显著增加了葡萄糖摄取。阿魏酸促进了棕榈酸所抑制的IRS-1的磷酸化，同时也抑制了棕榈酸诱导的IRS-1的磷酸化。阿魏酸激活了PI3K，进而刺激了Akt的磷酸化，这增加了质膜-葡萄糖转运蛋白4（PM-GLUT4）的表达，从而刺激葡萄糖摄取到胰岛素抵抗的肌肉细胞中。阿魏酸还通过Akt途径使糖原合成酶激酶3β（GSK3β）磷酸化，从而增加糖原合成。此外，阿魏酸显著促进了腺苷酸活化蛋白激酶（AMPK）的磷酸化，提高了PM-GLUT4水平和葡萄糖摄取。
这些结果表明，阿魏酸可能通过调节L6骨骼肌细胞中的IRS-1/Akt和AMPK途径来改善棕榈酸诱导的胰岛素抵抗。
