Lee Esder, Ryu Gyeong Ryul, Ko Seung-Hyun, Ahn Yu-Bae, Song Ki-Ho
Division of Endocrinology & Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Division of Endocrinology & Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Biochem Biophys Res Commun. 2017 Apr 1;485(2):328-334. doi: 10.1016/j.bbrc.2017.02.082. Epub 2017 Feb 21.
To investigate whether the activation of pancreatic stellate cells (PSCs) leads to pancreatic β-cell dysfunction in type 2 diabetes mellitus (T2DM).
The pancreases of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of T2DM, and patient with T2DM were analyzed. And the in vitro and in vivo effects of pirfenidone, an antifibrotic agent, on PSC activation, islet fibrosis, and β-cells were studied.
The extent of islet fibrosis and the percentage of activated PSCs, positive for α-smooth muscle actin, in the islets were significantly greater in OLETF rats compared with non-diabetic rats. Also, the extent of islet fibrosis in patients with T2DM was slightly greater compared with age- and BMI-matched non-diabetic patients. In rat PSCs cultured with high glucose for 72 h, pirfenidone produced decreases in cell proliferation, release of collagen, and the expression of fibronectin and connective tissue growth factor. Treatment of OLETF rats with pirfenidone for 16 weeks decreased the activation of PSCs and the extent of islet fibrosis, but did not enhance glucose tolerance, pancreatic insulin content, or β-cell mass.
Activated PSCs in islets might lead to islet fibrosis in T2DM. However, PSC activation itself might not contribute significantly to progressive β-cell failure in T2DM.
研究胰腺星状细胞（PSC）的激活是否会导致2型糖尿病（T2DM）患者的胰腺β细胞功能障碍。
分析T2DM动物模型大冢长-艾氏-德岛肥胖（OLETF）大鼠以及T2DM患者的胰腺。研究抗纤维化药物吡非尼酮对PSC激活、胰岛纤维化和β细胞的体外及体内作用。
与非糖尿病大鼠相比，OLETF大鼠胰岛纤维化程度以及胰岛中α平滑肌肌动蛋白阳性的活化PSC百分比显著更高。此外，与年龄和体重指数匹配的非糖尿病患者相比，T2DM患者的胰岛纤维化程度略高。在高糖培养72小时的大鼠PSC中，吡非尼酮可降低细胞增殖、胶原蛋白释放以及纤连蛋白和结缔组织生长因子的表达。用吡非尼酮治疗OLETF大鼠16周可降低PSC的活化和胰岛纤维化程度，但未改善葡萄糖耐量、胰腺胰岛素含量或β细胞量。
胰岛中活化的PSC可能导致T2DM中的胰岛纤维化。然而，PSC激活本身可能对T2DM中进行性β细胞衰竭的影响不大。
