Glucose and insulin tolerance tests in the rat on different days of gestation

To study insulin/glucose relationship during gestation, rats were studied on days 6, 12, 15, 18, 20 or 21 of pregnancy and the results were compared to values in sex-matched virgin control rats. Blood glucose levels were decreased on days 20 and 21 of gestation whereas plasma insulin levels appeared decreased on days 6 and 12, unchanged on day 15 and enhanced on days 18, 20 and 21 of gestation. Total pancreas insulin content was already augmented on day 6 of gestation and continued to increase with gestational time. With the exception of an increase in the 6-day-pregnant rats 22.5 min after an oral glucose load, blood glucose levels did not differ between 6- or 12-day-pregnant rats and virgin controls although plasma insulin levels reached higher values on these days. However, in the 15-day-pregnant rats, glucose tolerance after the glucose load was enhanced while plasma insulin levels did not differ from those in virgin rats during the first 30 min. In the 18-day-pregnant rat blood glucose was more increased but plasma insulin did not differ after the glucose load when compared to virgin rats, whereas 20- or 21-day-pregnant rats showed a glucose tolerance similar to that of virgin rats but their insulin levels shortly after the glucose load were higher. The hypoglycemic response to a high intravenous dose of insulin was decreased in 12-, 18-, 20- and 21-day-pregnant rats. Therefore, whereas in both the 6- and 12-day-pregnant rats there is an enhanced beta-cell response to the glucose insulinotropic effect and insulin responsiveness is reduced in 12-day-pregnant rats, the 15-day pregnant rat is in a transitory stage where both insulin sensitivity and the beta-cell response return to nonpregnant values. However, from 18 days of gestation on, there is an intense insulin-resistant condition which is only partially compensated by an enormous accumulation of insulin in the pancreas followed by a faster and larger insulin release after a glucose load.