Effects of long-term administration of an α-glucosidase inhibitor on the development of macroangiopathy in OLETF rats

We investigated the effects of a long-term administration of acarbose, an a-glucosidase inhibitor on visceral fat accumulation and arteriosclerotic lesions in OLETF rats modeling obesity of the visceral fat accumulation type. Male OLETF rats, at the age of 4 weeks, were fed with an experimental diet containing acarbose at a concentration of 0 (control), 20, or 40 mg/100 g diet (n = 20 for each), and the course of the animals was observed. Weight gains in the acarbose-treated groups were significantly lower than that of the control group. Oral glucose (2 g/kg) tolerance tests performed at the age of 30 weeks revealed significantly milder impairment of glucose tolerance and significantly lower blood IRI in the acarbose-treated animals than in the controls. As for body-fat distribution, significant decreases were observed in the visceral fat. In the histopathological examination of the coronary arteries removed at the age of 81 weeks, the control animals showed a slight degree of intimal irregularity and intimal hypertrophy. On the other hand, the acarbose-treated animals never showed such intimal changes. In conclusion, long-term administration of this alpha-glucosidase inhibitor prevented the development of arteriosclerotic lesions in large vessels in OLETF rats modeling obesity of the visceral fat accumulation type.