生殖内分泌および周産期医学領域におけるインスリンの意義

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Soskin, in his 1946 textbook, stated that insulin may be regarded as the dominant instrument in the symphony of endocrine action that results in normal carbohydrate metabolism. After almost half a century, great progress in the medical field has revealed that insulin plays more than even he described. Some aspects of important actions of insulin in our field as investigated in our laboratory are summarized below. 1. Role of insulin in reproductive endocrinology. (1) Correlation of insulin and testosterone in normal young women and patients with polycystic ovary syndrome (PCO). The sum of serum insulin values during 75g OGTT and serum testosterone values were positively correlated in normal women and patients with PCO. Glucose transport activities in isolated adipocytes from a typical PCO patient were decreased, but insulin binding activities were not, which indicates that insulin resistance in this patients is due to some post-receptor defects. (2) Insulin may be a risk factor of endometrial carcinoma. It is well-recognized that several diseases associate with hyperinsulinemia, such as obesity, PCO, diabetes mellitus, and hypertension are risk factors for endometrial carcinoma. The sum of the insulin values during OGTT was significantly higher in patients with endometrial carcinoma than in those without. 2. Role of insulin in perinatal medicine. (1) Increase in insulin secretion during pregnancy. High serum insulin concentration during OGTT, increased secretion of urinary C-peptide, and enhanced staining of insulin in B cells by the PAP method suggest that insulin secretion is enhanced during pregnancy. (2) Insulin resistance during pregnancy. Glucose utilization rate in both pregnant and progesterone-treated rats, as assessed by a glucose clamp technique, is significantly decreased as compared to nonpregnant rats. The technique of 2-deoxyglucose injection revealed that whole body insulin resistance is due to insulin resistance in individual insulin-sensitive tissues. The activities of 3-0-methyl-D-glucose transport in isolated rat skeletal muscle and human adipocytes were found to decrease during late pregnancy, but insulin binding activities were not. These results suggest that insulin resistance during pregnancy is due to some post-receptor mechanisms. (3) Physiological meaning of insulin in fetal growth. Glucose concentration levels in maternal plasma positively correlated with those in cord plasma, and insulin concentration in cord serum positively correlated with birth weight, which confirms the hyperglycemia-hyperinsulinism hypothesis by J. Pedersen. Decreased glucose utilization rate in maternal tissue, which is derived from increased insulin resistance, is a favorable mechanism for the fetus because it saves glucose for it. 3. Screening of carbohydrate intolerance during pregnancy. (1) When to administer 50g oral glucose challenge test (GCT). The Second International Workshop-Conference in Gestational Diabetes recommended that all pregnant women should receive a GCT during their 23 to 27 weeks of pregnancy. However, our results indicate that one-hour glucose and insulin values were significantly increased at 28 or later weeks of pregnancy. This means that 23 to 27 weeks of pregnancy is too early to detect pregnancy-induced changes in carbohydrate metabolism. (2) Rationale for screening mild carbohydrate intolerance during early pregnancy. The detection rate of gestational diabetes is highest during 28 to 40 weeks of pregnancy, but a considerable number of the IGT or borderline cases have already been found by early pregnancy. One-hour glucose value for GCT during early pregnancy was significantly correlated with birth weight. These results suggest that the screening of carbohydrate intolerance should be performed during early as well as late pregnancy. (3) Etiology of gestational diabetes. The peak insulin response to GCT during early pregnancy in women with mild carbohydrate intolerance was delayed. We propose the hy
社団法人日本産科婦人科学会の論文
1990-08-01

生殖内分泌および周産期医学領域におけるインスリンの意義

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