title: Grape seed proanthocyanidins ameliorate pancreatic beta-cell dysfunction and death in low-dose streptozotocin- and high-carbohydrate/high-fat diet-induced diabetic rats partially by regulating endoplasmic reticulum stress.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These findings suggest that GSPs might have auxiliary therapeutic potential for pancreatic beta-cell dysfunction and death in T2DM.
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing, PR, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing, PR, China.
authors.forename: Zhaofeng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing, PR, China.
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Dai
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing, PR, China.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing, PR, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Bao
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing, PR, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing, PR, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
keywords: Endoplasmic reticulum stress; Grape seed proanthocyanidins; High-carbohydrate/high-fat diet; Insulin; Pancreatic beta-cell failure; Streptozotocin; Type 2 diabetes mellitus