Wu Jinzi, Yan Liang-Jun
Department of Pharmaceutical Sciences, UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX, USA.
Diabetes Metab Syndr Obes. 2015 Apr 2;8:181-8. doi: 10.2147/DMSO.S82272. eCollection 2015.
Chronic hyperglycemia and the corresponding glucotoxicity are the main pathogenic mechanisms of diabetes and its complications. Streptozotocin (STZ)-induced diabetic animal models are useful platforms for the understanding of β cell glucotoxicity in diabetes. As diabetes induced by a single STZ injection is often referred to as type 1 diabetes that is caused by STZ's partial destruction of pancreas, one question often being asked is whether the STZ type 1 diabetes animal model is a good model for studying the mitochondrial mechanisms of β cell glucotoxicity. In this mini review, we provide evidence garnered from the literature that the STZ type 1 diabetes is indeed a suitable model for studying mitochondrial mechanisms of diabetic β cell glucotoxicity. Evidence presented includes: 1) continued β cell derangement is due to chronic hyperglycemia after STZ is completely eliminated out of the body; 2) STZ diabetes can be reversed by insulin treatment, which indicates that β cell responds to treatment and shows ability to regenerate; and 3) STZ diabetes can be ameliorated or alleviated by administration of phytochemicals. In addition, mechanisms of STZ action and fundamental gaps in understanding mitochondrial mechanisms of β cell dysfunction are also discussed.
慢性高血糖及相应的糖毒性是糖尿病及其并发症的主要致病机制。链脲佐菌素(STZ)诱导的糖尿病动物模型是理解糖尿病中β细胞糖毒性的有用平台。由于单次注射STZ诱导的糖尿病通常被称为1型糖尿病,是由STZ对胰腺的部分破坏所致,因此经常被问到的一个问题是,STZ诱导的1型糖尿病动物模型是否是研究β细胞糖毒性线粒体机制的良好模型。在这篇小型综述中,我们提供了从文献中收集的证据,表明STZ诱导的1型糖尿病确实是研究糖尿病β细胞糖毒性线粒体机制的合适模型。所呈现的证据包括:1)在STZ完全从体内清除后,β细胞持续紊乱是由于慢性高血糖所致;2)胰岛素治疗可逆转STZ糖尿病,这表明β细胞对治疗有反应并显示出再生能力;3)给予植物化学物质可改善或减轻STZ糖尿病。此外,还讨论了STZ的作用机制以及在理解β细胞功能障碍线粒体机制方面的基本差距。