Effects of miglitol, an α-glucosidase inhibitor, on glycaemic status and histopathological changes in islets in non-obese, non-insulin-dependent diabetic Goto-Kakizaki rats
Effects of miglitol, an α-glucosidase inhibitor, on glycaemic status and histopathological changes in islets in non-obese, non-insulin-dependent diabetic Goto-Kakizaki rats
复制标题
DOI：
10.1017/s0007114507742678
复制
发表时间：
2007-10-01
影响因子：
3.6
通讯作者：
Kumazawa, Toshihiko
中科院分区：
文献类型：
--
作者：
Goda, Toshinao;Suruga, Kazuhito;Kumazawa, Toshihiko
米格列醇是一种1-脱氧野尻霉素衍生物，是α-葡萄糖苷酶抑制剂。在本研究中，在Goto-Kakizaki（GK）大鼠（2型糖尿病动物模型）中研究了米格列醇急性（单次给药）和慢性（8周）经口给药的影响。米格列醇急性经口给药（1、3或10 m/kg体重）后，观察到米格列醇给药GK大鼠蔗糖负荷后血糖值在2 h内积分的增量血糖浓度（Δ AUC（0 - 2 h））呈剂量依赖性降低。在10 mg/kg剂量下，血糖的Delta AUC（0 - 2 h）与对照组相比降低了45%。米格列醇混合饲料（10 mg、20 mg或40 mg米格列醇/100 g对照饲料）经口给药8周后，与对照GK大鼠相比，接受40 mg米格列醇/100 g对照饲料米格列醇给药的GK大鼠第8周与第0周的HbA（1c）比值显著降低，但体重无变化。在口服葡萄糖耐量试验中，米格列醇导致血浆葡萄糖浓度的Δ AUC（0 - 2 h）轻微降低。此外，米格列醇处理轻微抑制了GK大鼠中β细胞质量的减少，并减轻了胰岛的不规则轮廓和纤维化。这些结果表明，米格列醇改善GK大鼠的高血糖状态和胰岛功能受损。以及防止GK大鼠胰岛的变性。
Miglitol, a 1-deoxynojirimycin derivative, is an alpha-glucosidase inhibitor. In the present study, the effects of acute (single-dose) and chronic (8-week) oral administration of miglitol in Goto-Kakizaki (GK) rats, an animal model of type 2 diabetes, were investigated. Dose-dependent decreases in incremental blood glucose concentrations integrated over a period of 2 h (Delta AUC(0-2 h)) for values of blood glucose after sucrose-loading in miglitol-treated GK rats were observed following an acute oral administration of miglitol (1, 3 or 10 m/kg body weight). At 10 mg/kg, the Delta AUC(0-2 h) of blood glucose was decreased by 45% compared with the control group. Following the oral administration of miglitol in a dietary mixture (10 mg, 20 mg or 40 mg miglitol/100 g control diet) for 8 weeks, the ratio of HbA(1c) at 8 weeks compared with 0 weeks in GK rats treated with 40 mg miglitol/100 g control diet miglitol was significantly decreased compared with control GK rats without changes in body weight. In oral glucose tolerance testing, miglitol caused a slight decrease in the Delta AUC(0-2 h) of plasma glucose concentration. In addition, miglitol treatment slightly inhibited the reduction in beta-cell mass, and lessened the irregular contours and fibrosis of the islets in GK rats. These results indicate that miglitol ameliorates the hyperglycaemic state of GK rats and the impaired function of the pancreatic islets. as well as preventing the degeneration of islets in GK rats.