Curcumin enhances recovery of pancreatic islets from cellular stress induced inflammation and apoptosis in diabetic rats.
Curcumin enhances recovery of pancreatic islets from cellular stress induced inflammation and apoptosis in diabetic rats.
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DOI：
10.1016/j.taap.2014.12.003
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发表时间：
2015-02
影响因子：
3.8
通讯作者：
K. Rashid;P. Sil
中科院分区：
文献类型：
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作者：
K. Rashid;P. Sil
据报道，植物化学物质姜黄素具有许多有益的作用。然而，在糖尿病条件下，其对葡萄糖稳态调节器官胰腺的有益作用的详细机制尚不清楚。本研究旨在探索姜黄素在八周龄雄性 Wistar 大鼠的 STZ 诱导的胰腺组织和细胞应激介导的糖尿病中的作用。通过腹腔内单剂量 STZ（65 毫克/公斤体重）诱发糖尿病。诱导糖尿病后，动物接受姜黄素治疗，剂量为 100 毫克/公斤体重，持续八周。使用各种生化测定、DNA 片段化、FACS、组织学、免疫印迹和 ELISA 确定潜在的分子和细胞机制。姜黄素治疗可降低血糖水平，增加血浆胰岛素并减轻氧化应激相关标志物。体内和体外实验结果显示，STZ给药组促炎细胞因子（TNF-α、IL1-β和IFN-γ）水平升高，细胞防御蛋白（Nrf-2和HO-1）和葡萄糖转运蛋白（GLUT-2）水平降低，同时内质网应激依赖性和非依赖性细胞凋亡信号分子（cleaved Caspase-12/9/8/3）水平升高。姜黄素治疗改善了所有不利变化，并帮助器官恢复正常生理机能。结果表明，姜黄素通过减弱炎症反应、抑制 ER/线粒体依赖性和独立的细胞凋亡途径以及它们之间的串扰来保护胰腺 β 细胞。这种独特性和不存在任何可检测到的副作用提出了使用该分子作为细胞应激介导的糖尿病的有效保护剂的可能性。
The phytochemical, curcumin, has been reported to play many beneficial roles. However, under diabetic conditions, the detail mechanism of its beneficial action in the glucose homeostasis regulatory organ, pancreas, is poorly understood. The present study has been designed and carried out to explore the role of curcumin in the pancreatic tissue of STZ induced and cellular stress mediated diabetes in eight weeks old male Wistar rats. Diabetes was induced with a single intraperitoneal dose of STZ (65 mg/kg body weight). Post to diabetes induction, animals were treated with curcumin at a dose of 100 mg/kg body weight for eight weeks. Underlying molecular and cellular mechanism was determined using various biochemical assays, DNA fragmentation, FACS, histology, immunoblotting and ELISA. Treatment with curcumin reduced blood glucose level, increased plasma insulin and mitigated oxidative stress related markers. In vivo and in vitro experimental results revealed increased levels of proinflammatory cytokines (TNF-α, IL1-β and IFN-γ), reduced level of cellular defense proteins (Nrf-2 and HO-1) and glucose transporter (GLUT-2) along with enhanced levels of signaling molecules of ER stress dependent and independent apoptosis (cleaved Caspase-12/9/8/3) in STZ administered group. Treatment with curcumin ameliorated all the adverse changes and helps the organ back to its normal physiology. Results suggest that curcumin protects pancreatic beta-cells by attenuating inflammatory responses, and inhibiting ER/mitochondrial dependent and independent pathways of apoptosis and crosstalk between them. This uniqueness and absence of any detectable adverse effect proposes the possibility of using this molecule as an effective protector in the cellular stress mediated diabetes mellitus.