妊娠時の糖代謝に関する内分泌学的検討:とくにInsulinおよびC-peptideについて

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It has been established that insulin is synthesized as proinsulin within the pancreatic beta cell and then secreted together with connecting peptide, or C-peptide, which forms the major portion of the link between the insulin A and B chains in the proinsulin molecule. And it is generally accepted that C-peptide, unlike insulin, is not degraded by the liver. It is impossible to measure the serum insulin concentrations by the usual method of radioimmunoassay in subjects treated with exogenous insulin. While C-peptide is specific in its structure to species so that it is possible to measure its concentrations in such subjects. To assess the effect of pregnancy on insulin secretion by the pancreatic beta cell and its metabolic clearance, the following studies were performed during mid and late pregnancy and also 1 week and 4 weeks post partum. Glucose, insulin and C-peptide concentrations were measured during basal fasting conditions and following the administration of oral glucose or intravenous arginine. According to the recommendatory criteria of the Japan diabetic society, the carbohydrate metabolic function was classified as normal, borderline and diabetic. During late pregnancy, the mean value ± SEM for serum IRI concentrations after an overnight fast had a tendency to decrease in diabetic (8.6 ± 0.7 μU/ml) as compared to normal (10.4 ± 0.9 μU/ml). Fasting values in any group during pregnancy had a tendency to increase against the respective groups of non-pregnant women. During 50 g oral glucose tolerance tests (OGTT) in normal, it reached a peak value of 45.1 ± 3.8 μU/ml at 30 min. The total area under the insulin concentration curve was the largest in borderline followed by normal and diabetic. The fasting serum CPR in normal during late pregnancy was 2.56 ± 0.16 ng/ml and peaked at 7.52 ± 0.58 ng/ml 90 min. after an oral glucose administration. Then it fell to 4.63 ± 0.28 ng/ml at 180 min., which was higher than the fasting values. In borderline and diabetic, the fasting values for CPR were 2.11 ± 0.14 ng/ml and 2.10 ± 0.14 ng/ml, respectively. The area for CPR was the largest in borderline followed by normal and diabetic which was similar to the results for IRI. These results indicate that the response pattern of CPR during OGTT paralleled that of IRI in carbohydrate metabolic function. And also CPR response was slower in the rate, as compared to IRI. It was possible to measure CPR concentrations in insulin-treated diabetic pregnant women with the usual method of RIA. The measured response of CPR during OGTT in these patients was the slowest and weakest. The molar ratios of C-peptide to insulin were calculated. During pregnancy in normal, the ratio was 10.2 ± 1.8 in fasting and fell to the lowest values of 5.3 ± 0.5 at 30 min. after glucose administration, which tended to be higher than that of non-pregnant women at any time of OGTT. A significant correlation was found between serum IRI and CPR (r=0.763, p<0.001) during OGTT in pregnancy as well as in non-pregnancy. The incremental ratios of serum IRI and CPR to plasma glucose from a state of fasting to 30 min. after glucose administration were the highest in normal and the lowest in diabetic in both pregnant and non-pregnant women. From mid to late pregnancy, the levels of CPR during OGTT were significantly elevated, while those of IRI were slightly and not significantly elevated. At 1 week after delivery, both IRI and CPR levels were significantly decreased, particularly in IRI, as compared to late pregnancy. From 1 week to 4 weeks after delivery, IRI was slightly but significantly elevated despite no change for CPR. During 30 g arginine infusion tests for 30 min. in pregnancy, IRI had two peaks at 5 min. and 30 min. While CPR was raised rapidly after the start of the infusion, it sustained high levels for 30 min. without fractionation.
一般社団法人日本内分泌学会の論文

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村田和平
三重大学医学部産科婦人科

妊娠時の糖代謝に関する内分泌学的検討:とくにInsulinおよびC-peptideについて

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