Kim Ji-Won, Ko Seung-Hyun, Cho Jae-Hyoung, Sun Chenglin, Hong Oak-kee, Lee Seung-Hwan, Kim Ji-Hyun, Lee Kang-Woo, Kwon Hyuk-Sang, Lee Jung-Min, Song Ki-Ho, Son Ho-Young, Yoon Kun-Ho
Department of Endocrinology and Metabolism, The Catholic University of Korea, Seoul, Korea.
Front Biosci. 2008 May 1;13:6022-33. doi: 10.2741/3133.
Recent morphologic analyses of human pancreases strongly suggest that a decreased beta-cell mass is observed from the early stages of diabetes and is caused by accelerated apoptosis of the beta-cells. In this article, we propose that fibrotic islet destruction might be one of the important pathogenic mechanisms of the limited capacity of beta-cell proliferation and accelerated apoptosis in diabetic patients. We have found that pancreatic stellate cells (PSCs) are involved in the progression of islet fibrosis in type 2 diabetes. High concentrations of glucose and insulin in islets contribute to PSC activation and proliferation through angiotensin II type 2 (ATII) signaling pathway, although the exact mechanisms remain to be confirmed. Angiotensin-converting enzyme inhibitors attenuate fibrotic islet destructions and that these have some beneficial effects on glucose tolerance. We suggest that PSCs might play a major role for the fibrotic islet destruction in patients with type 2 diabetes, and suppression of PSCs activation and proliferation might be one of the reasonable target to prevent and delay the progression of the type 2 diabetes mellitus.
近期对人类胰腺的形态学分析有力地表明，从糖尿病早期阶段就可观察到β细胞数量减少，且这是由β细胞加速凋亡所致。在本文中，我们提出纤维化胰岛破坏可能是糖尿病患者β细胞增殖能力受限和加速凋亡的重要致病机制之一。我们发现胰腺星状细胞（PSC）参与2型糖尿病中胰岛纤维化的进展。胰岛中高浓度的葡萄糖和胰岛素通过血管紧张素II 2型（ATII）信号通路促进PSC的激活和增殖，尽管确切机制仍有待证实。血管紧张素转换酶抑制剂可减轻纤维化胰岛破坏，且对葡萄糖耐量有一些有益作用。我们认为PSC可能在2型糖尿病患者的纤维化胰岛破坏中起主要作用，抑制PSC激活和增殖可能是预防和延缓2型糖尿病进展的合理靶点之一。
