Silibinin protects GLUTag cells from PA-induced injury via suppressing endoplasmic reticulum stress

Abstract

Abstract Silibinin is a natural extract exhibiting anti-diabetic effects. Lipotoxicty induced by excessive accumulation of free fatty acids (FFAs) leads to both insulin resistance and β cell insufficiency, which can trigger the pathogenesis of type 2 diabetes mellitus (T2DM). Glucagon-like peptide-1 (GLP-1), an intestinal hormone mainly secreted from L cells, regulates insulin production and sensitivity, and protection of the functional GLP-1 producing L cells appears to be a potential therapeutic strategy for T2DM patients. The current study aims to determine the protective effect of silibinin against palmitic acid (PA)-induced damage in L cell line GLUTag cells. In PA-treated GLUTag cells, silibinin was shown to decrease endoplasmic reticulum (ER) stress-mediated apoptosis. Furthermore, the autophagy inhibitor 3-methyladenine (3-MA) reversed PA-induced apoptosis, indicating that protective autophagic response was accompanied by apoptosis in GLUTag cells. Based on the estrogen-like effects of silibinin and the role of estrogen receptors in regulating glycolipid metabolism, the involvement of estrogen receptors in protective effects of silibinin in GLUTag cells were further determined. The results showed estrogen receptor α and β-specific inhibitors reversed the inhibitory impact of silibinin on ER stress. Our study demonstrated that silibinin protects GLUTag cells from PA-induced injury by decreasing ER stress under the regulation of estrogen receptor α and β.