Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Biochem Biophys Res Commun. 2013 Apr 12;433(3):292-7. doi: 10.1016/j.bbrc.2013.02.095. Epub 2013 Mar 13.
Islet fibrosis, pancreatic β-cell dysfunction, and β-cell apoptosis are features of pancreatic diabetes and type 2 diabetes; however, the underlying mechanisms remain largely unknown. We hypothesized that pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, might affect the phenotype of pancreatic β-cells. α-Smooth muscle actin (a marker of activated PSC)-positive cells were found within and around the fibrotic islets. Indirect co-culture with PSCs reduced insulin expression and induced apoptosis in RIN-5F pancreatic β-cells. Induction of β-cell apoptosis was associated with activation of the caspase pathway and mitochondrial depolarization. Diphenylene iodonium, an inhibitor of PSC activation, inhibited islet fibrosis and protected islets in vivo. Our findings suggest a novel mechanism linking PSCs, islet fibrosis, and diabetes mellitus.
胰岛纤维化、胰腺β细胞功能障碍和β细胞凋亡是胰腺糖尿病和 2 型糖尿病的特征；然而，其潜在机制在很大程度上尚不清楚。我们假设胰腺星状细胞（PSC），即胰腺中主要的促纤维化细胞类型，可能会影响胰腺β细胞的表型。在纤维化的胰岛内和周围发现了α平滑肌肌动蛋白（激活的 PSC 的标志物）阳性细胞。与 PSCs 间接共培养会降低 RIN-5F 胰腺β细胞中的胰岛素表达并诱导其凋亡。β细胞凋亡的诱导与半胱天冬酶途径的激活和线粒体去极化有关。PSC 激活的抑制剂二苯基碘鎓可抑制胰岛纤维化并在体内保护胰岛。我们的研究结果表明了一种新的机制，将 PSCs、胰岛纤维化和糖尿病联系在一起。
