妊娠糖尿病に関する実験的研究、とくに妊娠糖尿病ラット胎仔に及ぼすインスリン治療の効果

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With regard to the progress of the treatment of diabetes mellitus, the clinical cases of diabetic pregnancy are increasing, and sb the effects of maternal hyperglycemia on the fetuses or newborns become a very important problem. There are many reports which state about the development of newborns from diabetic pregnant mothers and about the dynamics of plasma insulin (IRI) levels or C-peptide reactivities (CPR) of them. However, there are few reports which research for the effects of insulin treatment of diabetic pregnant mother on the fetus. Concerning to experimental animals, there are also a few reports about the effects of insulin treatment to diabetic pregnant animals on their fetuses. The present investigation was aimed to observe the effects of insulin treatment to diabetic pregnant rats on the fetuses. Vergin Wistar female rats weighing 200 to 300g were caged overnight with male rats. The mated females were isolated and the gestational age was calculated from noon of that day (zero). Diabetic pregnant rats were administered intravenous injection of 50mg/kg body weight of streptozotocin (STZ) (Upjohn, Kalamazoo) in 0.4ml of 0.01M citrate buffer into jugular veins under light ether anaesthesia on the 5 day of gestation. On the contrary, normal control group (I group) rats were injected only 0.4ml of citrate buffer by the same way. All rats were fed ad libitum in the metabolic cages and the urinary glucose excretion and the urine volume were measured everyday. III group rats were treated with subcutaneous injection of Lente Insulin (from 2u. to 6u.) everyday from the 13 day to the 19 day of gestation. II group rats were injected saline everyday by the same way. Maternal blood samples were collected from the jugular veins by syringes including EDTA-2Na and aprotinin under light ether anaesthesia on the 5, 12 and 20 day of gestation. Each fetus and each placenta were taken out one after another by hysterotomy on the 20 day of gestation. The fetus was decapitated and fetal blood samples were collected in cooled polyethylene tubes. The fetal and maternal pancreases were removed, extracted and homogenized by ultrasonifier in 2M acetic acid. The tissue samples were lyophylized and kept in freezer (-20℃) until radioimmunoassay (RIA). The plasma glucose concentration was measured by glucose oxidase method, the insulin (IRI) and the somatostatin (IRS) were determined by RIA using double-antibody and the glucagon (lRG) was determined by RIA using OAL-123 as an antibody and charcoal-dextran. The protein was measured by the Lowry's method. II group rats were not able to gain the body weight and showed markedly high blood glucose level (413±37mg/100ml). On the other hand, III group rats gained the body weight, and there were no significant weight differences compared to I group rats on the 20 day of gestation. Although there were no significant differences in the fetal body weights between III group and I group, the fetal body weight of II group was significantly lower than that of I group. Concerning the fetal pancreas weight, there were no significant differences among all groups. The fetal plasma glucose was showed a significant correlation (r=0.92) with the maternal plasma glucose. Comparing with I group, the fetal plasma IRI of II group decreased, but that of III group increased significantly. The fetal pancreatic insulin content of the II group diminished significantly compared to that of I group. Whlie the fetal pancreatic insulin content of III group was increased after insulin treatment compared to that of II group. Several authors have already reported on the hyperinsulinemia in fetuses and its important role as a growth factor before birth. In this experiment, the fetal plasma IRI in I group was remarkably higher than that of the mothers. On the other hand, the fact that the fetal plasma IRI and the fetal pancreatic insulin content diminished in II group suggested that the fetal development was impaired by deficiency of insulin. After the fetal plasma glucose decreased by insulin replacement of the maternal rats, the fetal plasma IRI, the fetal pancreatic insulin content and the fetal body weight recovered in some degree. My experimental results suggest that the adequate insulin treatment of diabetic pregnant rats can make a good condition for the fetal development. In II group, the fetal plasma IRG was suppressed significantly and the fetal pancreatic glucagon and somatostatin content increased significantly. These results suggested that the fetal pancreas had the ability to adjust its secretion according to the various changes of the environmental substances, such as hyperglycemia and so forth.
神戸大学の論文

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河原啓
神戸大学医学部内科学第二講座

妊娠糖尿病に関する実験的研究、とくに妊娠糖尿病ラット胎仔に及ぼすインスリン治療の効果

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