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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

Toshinao Godaa1 c1, Kazuhito Surugaa1, Akiko Komoria1, Sachi Kuranukia1, Kazuki Mochizukia1, Yumi Makitaa2 and Toshihiko Kumazawaa3 a1 Laboratory of Nutritional Physiology and COE Program in the 21st Century, University of Shizuoka School of Food and Nutritional Sciences, 52-1 Yada, Shizuoka 422-8526, Japan a2 Mitsubishi Chemical Safety Institute Ltd., Ibaraki, Japan a3 Sanwa Kagaku Kenkyusho Co., Ltd., Nagoya, Japan

Article author query goda t   suruga k   komori a   kuranuki s   mochizuki k   makita y   kumazawa t

Abstract

Miglitol, a 1-deoxynojirimycin derivative, is an α-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 (ΔAUC_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 mg/kg body weight). At 10 mg/kg, the ΔAUC_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 ΔAUC_0–2 h of plasma glucose concentration. In addition, miglitol treatment slightly inhibited the reduction in β-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.

(Received October 18 2006)

(Revised February 21 2007)

(Accepted March 09 2007)

Key Words:Miglitol; α-Glucosidase inhibitor; β-Cell mass; GK rats

Correspondence:

^c1 Corresponding author: Dr Toshinao Goda, fax +81 54 264 5565, email gouda@fns1.u-shizuoka-ken.ac.jp

Footnotes

Abbreviations: ΔAUC_0–2 h, incremental blood glucose concentration integrated over a period of 2 h; GK, Goto-Kakizaki