Oral administration of soybean peptide Vglycin normalizes fasting glucose and restores impaired pancreatic function in Type 2 diabetic Wistar rats
Oral administration of soybean peptide Vglycin normalizes fasting glucose and restores impaired pancreatic function in Type 2 diabetic Wistar rats
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口服大豆肽 Vglycin 可使 2 型糖尿病 Wistar 大鼠的空腹血糖正常化并恢复受损的胰腺功能
DOI：
10.1016/j.jnutbio.2014.04.010
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发表时间：
2014-09-01
影响因子：
5.6
通讯作者：
Chen, Zhengwang
中科院分区：
文献类型：
--
作者：
Jiang, Hua;Fen, Jueping;Chen, Zhengwang
Vglycin是从豌豆种子中分离的天然37个残基的多肽，其中六个半半胱氨酸残基嵌入三对二硫键中，其对消化酶具有抗性并且具有抗糖尿病潜力。为了研究Vglycin在体内的药理学活性并检查所涉及的机制，检查了Vglycin在糖尿病大鼠中的治疗效果。采用高脂饮食和多次腹腔注射链脲佐菌素诱导Wistar大鼠糖尿病模型。糖尿病大鼠每天用Vglycin治疗4周。每周测定体重、摄食量、空腹血糖和胰岛素水平。在第29天进行葡萄糖和胰岛素耐量试验。随后，通过免疫印迹法检测肝脏和胰腺中的p-Akt水平以及胰腺中裂解的PARP、Pdx-1和胰岛素水平。分别采用苏木精-伊红染色和免疫组织化学方法观察胰腺形态学和胰岛素表达。此外，使用人肝源性细胞系来探索Vglycin对胰岛素敏感性和葡萄糖摄取的体外影响。在糖尿病大鼠中用V甘氨酸长期治疗使空腹葡萄糖水平正常化。葡萄糖稳态的改善和由恢复的胰岛素信号传导介导的胰岛素敏感性增加可能有助于减少食物摄入和减轻体重。甘氨酸保护胰腺细胞免受链脲佐菌素的损伤。尽管受损β细胞中胰岛素的合成和分泌没有显著升高，但在V甘氨酸处理组中胰岛形态得到改善。这些结果表明，Vglycin可用于2型糖尿病，用于恢复受损的胰岛素信号传导、葡萄糖耐量和胰腺功能。(C)2014爱思唯尔公司All rights reserved.
Vglycin, a natural 37-residue polypeptide isolated from pea seeds in which six half-cysteine residues are embedded in three pairs of disulfide bonds, is resistant to digestive enzymes and has antidiabetic potential. To investigate the pharmacological activity of Vglycin in vivo and to examine the mechanisms involved, the therapeutic effect of Vglycin in diabetic rats was examined. Diabetes was induced in Wistar rats by high-fat diet and multiple streptozotocin intraperitoneal injections. Diabetic rats were treated daily with Vglycin for 4 weeks. Body weight, food intake, fasting plasma glucose and insulin levels were assayed weekly. Glucose and insulin tolerance tests were conducted on Day 29. Subsequently, levels of p-Akt in the liver and pancreas and cleaved PARP, Pdx-1 and insulin in the pancreas were detected by immunoblotting. The morphology of the pancreas and the insulin expression in the pancreas were analyzed by hematoxylin eosin staining and immunohistochemistry, respectively. Furthermore, human liver-derived cell lines were used to explore the in vitro effects of Vglycin on insulin sensitivity and glucose uptake. Chronic treatment with Vglycin normalized fasting glucose levels in diabetic rats. The improvement in glucose homeostasis and the increased insulin sensitivity mediated by restored insulin signaling likely contributed to decreased food intake and reduced body weight. Vglycin protected pancreatic cells from damage by streptozotocin. Although insulin synthesis and secretion in impaired beta-cell were not significantly elevated, islets morphology was improved in the Vglycin-treated groups. These results suggest that Vglycin could be useful in Type 2 diabetes for restoring impaired insulin signaling, glucose tolerance and pancreatic function. (C) 2014 Elsevier Inc. All rights reserved.