糖尿病と妊娠に関する実験的研究, とくに糖尿病妊娠ラット胎仔に及ぼすインスリン治療の効果

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Through the development of treatment of diabetes mellitus, diabetic cases of pregnancy have been increasing, and the effects of maternal hyperglycemia and insulin-treated hypoglycemia on the growth and life of fetuses and newborns are becoming very important problems. However, it is difficult for us to investigate the fetuses of human diabetic mothers as experimental models. Although many reports deal with the development of newborns of diabetic mothers and about their secretory changes of insulin and C-peptide reactivity, there have been few reports concerning the effects of severe diabetes on pregnancy and the effects of insulin treatment on fetuses. Concerning experimental animals, there are also few reports about the effects of insulin treatment on diabetic pregnant animals. We conducted the present investigation to determine the effects of insulin treatment on the growth and metabolism of the fetuses of diabetic pregnant rats. Virgin female Wistar rats weighing 200-300 g were caged overnight with male rats. The mated females were isolated and the gestational age was calculated from noon of this day (zero). Seventeen of 24 pregnant rats received a rapid intravenous injection of 50 mg/ kg body weight of streptozotocin (STZ) in 0.4 ml of 0.01 M citrate buffer (pH 4.5) immediately after blood samples were collected through the jugular vein under light ether anaesthesia on the 5th day of gestation. Seven pregnant rats were injected with only 0.4 ml of citrate buffer and served as the controls. These rats were divided into four groups, and each group was named as follows : Normal pregnant rats group (group I, n=7), diabetic pregnant rats group (group II, n=6) and insulin-treated diabetic pregnant rats group (group III : plasma glucose level 60-300 mg/di, n=6 and group IV : plasma glucose level below 60 mg/di, n=5). Group III and IV rats were treated with a subcutaneous injection of Lente Insulin (from 2 u. to 6 u.) every day from the 13th to the 19th day of gestation. Group II rats were injected with saline every day in the same way. Maternal blood samples were collected under light ether anaesthesia after feeding ad libitum on the 5th and 12th days of gestation. On the 20th day of gestation, the pregnant rats were anaesthetized by an intraperitoneal injection of sodium pentobarbital, and blood samples were collected in the manner stated above. Each fetus and placenta was taken out individually by hysterotomy. Subsequently the fetal and maternal pancreases were removed, extracted and homogenized by ultrasonifier in cooled 2M acetic acid. The tissue samples were lyophilized for radioimmunoassay (RIA). Plasma glucose was measured by the glucose oxidase method. Insulin concentrations (IRI) and somatostatin concentrations (IRS) were determined by the RIA using double-antibody and glucagon concentrations (IRG) determined by the dextran-charcoal RIA method using OAL-123. Compared to group I maternal rats, group II maternal rats were not able to gain body weight and showed a significantly high blood glucose level (413 ± 37 mg/di). On the other hand, group III and IV rats were able to gain body weight, and there were no significant weight differences between these rats and gorup I rats on the last day. Although there were no significant differences in the fetal body weight between groups III and I, the fetal body weights of groups II and IV were significantly lower than those of group I. There were no significant differences in fetal pancreas weight among all groups by the method of comparing one group with the others. The fetal plasma glucose level of each group on the 20th day of gestation showed a significant correlation (r= 0.92) with maternal plasma glucose. Compared with group I, the fetal plasma IRI levels of groups II and IV were low, but that of group III was significantly higher. The fetal pancreatic insulin contents of groups II, III and IV were significantly lower than those of group I.

糖尿病と妊娠に関する実験的研究, とくに糖尿病妊娠ラット胎仔に及ぼすインスリン治療の効果

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