The α-glucosidase inhibitor miglitol delays the development of diabetes and dysfunctional insulin secretion in pancreatic β-cells in OLETF rats

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat, an animal model of type 2 diabetes, exhibits obesity, hyperglycemia and hyperlipidemia, with late onset of chronic and slowly progressive hyperinsulinemia. In this study, we examined effects of long-term dietary supplementation with the alpha-glucosidase inhibitor miglitol on the development of diabetes and the reduction of beta-cells in the pancreas of OLETF rats. The OLETF rats were fed a control diet or a diet containing 800 ppm miglitol (miglitol diet) for 65 weeks from pre-onset stage (5 weeks old). The non-fasting blood glucose concentrations gradually increased in OLETF rats fed the control diet and, at week 64, were significantly higher than those in OLETF rats fed the miglitol diet and age-matched Long-Evans Tokushima Otsuka (LETO) rats, which are control, non-diabetic, non-obese rats of the same strain. Oral glucose tolerance tests revealed that OLETF rats fed the control diet showed pronounced impaired glucose tolerance, but those fed the miglitol diet did not. Furthermore, insulin concentrations after glucose-loading were significantly lower in OLETF rats fed the control diet than in those fed the miglitol diet. The islets of 65-week-old OLETF rats fed the control diet showed significant fibrosis and loss of beta-cells, while those of age-matched control LETO rats had a normal appearance. Feeding OLETF rats a miglitol diet reduced fibrosis and the loss of beta-cells. Our results suggest that dietary supplementation with miglitol from pre-onset stage in OLETF rats delays the onset and development of diabetes and preserves the insulin secretory function of pancreatic islets. (C) 2009 Elsevier B.V. All rights reserved.