Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing, PR, China.
Nutr Metab (Lond). 2013 Jul 21;10:51. doi: 10.1186/1743-7075-10-51. eCollection 2013.
It is increasingly being realized that failure of pancreatic beta cells to secrete enough insulin to adequately compensate for obesity and insulin resistance is the primary defects of type 2 diabetes mellitus (T2DM). Pancreatic beta cells possess a highly developed and active endoplasmic reticulum (ER), reflecting their role in folding, export and processing of newly synthesized insulin. ER stress-induced pancreatic beta-cell failure is a novel event in the pathogenesis of T2DM. Some studies with antioxidants indicated a beneficial impact on ER stress. Our previous study found that strong antioxidants, grape seed proanthocyanidins (GSPs), ameliorated ER stress to protect skeletal muscle from cell death in type 2 diabetic rats. The present study continued to investigate the effect of GSPs on beta-cell failure and ER stress in diabetic pancreas.
Male Sprague-Dawley rats made type 2 diabetic with 2 injections of 25 mg/kg streptozotocin and 8 weeks of the high-carbohydrate/high-fat diet were fed a basal diet with or without GSPs administration for 16 weeks. Oral glucose tolerance, plasma glucose, serum insulin and the score of beta-cell function were measured. Morphological observation was performed by light and electron microscopic analyses. Islet cell apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling staining. Additionally, the level of insulin and the expression of ER stress markers in pancreatic islets were also studied using immunohistochemical staining.
After 16 weeks treatment, the score of beta-cell function and the abnormal oral glucose tolerance of diabetic rats were partially reversed by GSPs treatment. The efficacious effect of GSPs was also manifested in the amelioration of pancreatic damage and ER dilatation by microscopic analyses. Moreover, GSPs treatment increased normal insulin content and decreased the number of apoptotic cells in diabetic islets. Importantly, GSPs treatment partially alleviated ER stress by decreasing some ER stress markers.
These findings suggest that GSPs might have auxiliary therapeutic potential for pancreatic beta-cell dysfunction and death in T2DM.
越来越多的人意识到，胰腺β细胞不能分泌足够的胰岛素来充分补偿肥胖和胰岛素抵抗，这是 2 型糖尿病（T2DM）的主要缺陷。胰腺β细胞具有高度发达和活跃的内质网（ER），反映了它们在新合成胰岛素的折叠、输出和加工中的作用。ER 应激诱导的胰腺β细胞衰竭是 T2DM 发病机制中的一个新事件。一些抗氧化剂的研究表明对 ER 应激有有益的影响。我们之前的研究发现，强抗氧化剂葡萄籽原花青素（GSPs）改善 ER 应激，保护 2 型糖尿病大鼠的骨骼肌细胞免于死亡。本研究继续研究 GSPs 对糖尿病胰腺中β细胞衰竭和 ER 应激的影响。
雄性 Sprague-Dawley 大鼠用 2 次 25mg/kg 链脲佐菌素和 8 周高碳水化合物/高脂肪饮食诱导 2 型糖尿病，然后给予基础饮食或 GSPs 治疗 16 周。测量口服葡萄糖耐量、血浆葡萄糖、血清胰岛素和β细胞功能评分。通过光镜和电镜分析进行形态学观察。末端脱氧核苷酸转移酶介导的 dUTP 生物素缺口末端标记染色测定胰岛细胞凋亡。此外，还通过免疫组织化学染色研究胰岛中胰岛素水平和 ER 应激标志物的表达。
经过 16 周的治疗，GSPs 治疗部分逆转了糖尿病大鼠的β细胞功能评分和异常口服葡萄糖耐量。GSPs 的有效作用还表现在通过显微镜分析改善了胰腺损伤和 ER 扩张。此外，GSPs 治疗增加了正常胰岛素含量，减少了糖尿病胰岛中凋亡细胞的数量。重要的是，GSPs 治疗通过降低一些 ER 应激标志物部分缓解了 ER 应激。
这些发现表明 GSPs 可能对 T2DM 中的胰腺β细胞功能障碍和死亡具有辅助治疗潜力。
