A transgenic dwarf rat model as a tool for the study of calorie restriction and aging

We have previously reported a long-lived transgenic dwarf rat model, in which the growth hormone (GH)-insulin like growth factor (IGF)-1 axis was selectively suppressed by overexpression of antisense GH transgene. Rats heterozygous for the transgene (tg/-) manifest phenotypes similar to those in calorie-restricted (CR) rats. To further characterize the transgenic rat in comparison with CR rats, the present study evaluated glucose and insulin tolerance in tg/- and control Wistar (-/-) rats at 6-9 months of age. Rats were fed ad libitum (AL) or 30% CR from 6 weeks of age. In CR rats, glucose disposal after glucose load was facilitated without any significant surge of serum insulin, and insulin tolerance test also indicated increased insulin sensitivity. In transgenic rats, similar findings were observed after glucose and insulin load, and CR in tg/- rats further facilitated glucose disposal during glucose and insulin tolerance tests. These findings suggest the presence of both common and separate mechanisms regulating the glucose-insulin system between CR and the reduced GH-IGF-1 axis paradigms. The transgenic rat model is, therefore, a useful one for studies of CR and aging.