Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Biochem Biophys Res Commun. 2011 Sep 23;413(2):264-9. doi: 10.1016/j.bbrc.2011.08.083. Epub 2011 Aug 27.
Vaspin, an adipocytokine recently identified in a rat model of type 2 diabetes, has been suggested to have an insulin-sensitizing effect. However, the exact mechanism underlying this action has not been fully elucidated. Furthermore, the specific function of vaspin is largely unknown, especially in vascular cells. We examined whether vaspin affects the insulin-signaling pathway in cultured endothelial cells and is capable of preventing free fatty acid (FFA)-induced apoptosis in endothelial cells through its insulin sensitizing effect, specifically, through its stimulatory effect on PI3-kinase/Akt signaling pathways. Vaspin significantly increased Akt phosphorylation and prevented the impairment of Akt phosphorylation by linoleic acid (LA) in insulin-stimulated endothelial cells, which effects were abolished by pretreatment with the PI3-kinase inhibitor, Wortmannin. Moreover, pretreatment with vaspin prevented LA-induced apoptosis in insulin-stimulated endothelial cells; this anti-apoptotic effect of vaspin was also eliminated by pretreatment with Wortmannin. The present study indicates that vaspin protects vascular endothelial cells from FFA-induced apoptosis through upregulation of the PI3-kinase/Akt signaling pathway. Our study is the first to demonstrate that vascular cells can be targets of vaspin. Our results further suggest that vaspin could have beneficial effects on the atherosclerosis.
内脏脂肪素（vaspin）是一种新近在 2 型糖尿病大鼠模型中发现的脂肪细胞因子，被认为具有胰岛素增敏作用。然而，其作用的确切机制尚未完全阐明。此外，内脏脂肪素的确切功能在很大程度上尚不清楚，特别是在血管细胞中。我们研究了内脏脂肪素是否会影响培养的内皮细胞中的胰岛素信号通路，以及它是否能够通过其胰岛素增敏作用，特别是通过刺激 PI3-激酶/Akt 信号通路，预防游离脂肪酸（FFA）诱导的内皮细胞凋亡。内脏脂肪素可显著增加 Akt 磷酸化，并可防止 linoleic acid（LA）抑制胰岛素刺激的内皮细胞中 Akt 磷酸化，这种作用可被 PI3-激酶抑制剂 Wortmannin 所阻断。此外，内脏脂肪素预处理可预防 LA 诱导的胰岛素刺激的内皮细胞凋亡；这种内脏脂肪素的抗凋亡作用也可被 Wortmannin 预处理所消除。本研究表明，内脏脂肪素通过上调 PI3-激酶/Akt 信号通路来保护血管内皮细胞免受 FFA 诱导的凋亡。我们的研究首次表明血管细胞可能是内脏脂肪素的靶标。我们的结果进一步表明，内脏脂肪素可能对动脉粥样硬化具有有益作用。
