Insulin receptor binding to erythrocytes in the first half of pregnancy is increased in healthy pregnant women as compared with non-pregnant or gestational diabetic women.

Insulin binding to erythrocytes was measured longitudinally by a competitive radioreceptor assay in 21 healthy pregnant (HP) and 20 well-controlled gestational diabetic women (GD) in 4-week intervals throughout pregnancy and at day 4 post-partum. Maximum insulin binding (maxbdg) at weeks 8-14 was increased (P < 0.001) in HP (median: 6.0%) but not in GD (median: 2.7%) as compared with non-pregnant control subjects (C) (median: 3.6%; previously reported: Clin. Chim. Acta 1992;207:57-71) due to an increased number of high-affinity insulin receptors. Throughout gestation the binding decreased continuously, to reach at term the levels found in C. In GD maxbdg remained close to the level of C throughout pregnancy. Binding differences between HP and GD were independent of the body mass index. Maxbdg did not differ between diet- and insulin-treated patients. It was higher in women whose offspring had low umbilical cord insulin levels (< 10 mu units/ml). The findings suggest that (a) higher insulin binding in HP could contribute to the improved glucose tolerance in early pregnancy and (b) the lack of increase in insulin binding during early pregnancy in gestational diabetes might be one factor leading to the manifestation of the disease in late pregnancy. However, it must be kept in mind that insulin receptors on erythrocytes do not necessarily resemble those on the major target tissues of insulin.

Insulin binding to erythrocytes of nonpregnant women: a reevaluation, underlining the importance of body weights even in nonobese subjects.

Insulin binding to erythrocytes was measured in 18 healthy, non-obese women in the follicular phase and in 6 women in the mid-luteal phase of the same menstrual cycle. The presence of 55 nM and 220 nM monoclonal anti-IGF I receptor antibody (alpha-IR3) reduced only the number of low affinity binding sites for insulin by 20% and 33%, respectively. Women with relative body weights 110-119% had a lower number of high affinity receptors and an increased high affinity compared to women with relative body weights 91-109%. In women with relative body weights greater than or equal to 100%, maximum specific binding and high affinity constants increased and the receptor numbers decreased from the follicular to the luteal phase, whereas in women with relative body weights less than 100% the parameter changes were reverted. The data indicate: (1) erythrocytes contain two different classes of binding sites for insulin, (2) IGF I receptors might contribute to low-affinity binding of insulin to erythrocytes and (3) the relative body weight must be considered even for 'non-obese' control groups used in insulin binding studies of various clinical conditions.

Insulin and glucose do not affect the glycogen content in isolated and cultured trophoblast cells of human term placenta.

The influence of insulin and glucose on the glycogen content of isolated trophoblast cells was measured for the first time. The cells were obtained by tryptic digestion of villous tissue from term placentae of 15 healthy women, further purified on a Percoll gradient and enriched by employing a monoclonal anti HLA class-I antibody. The cells stained intensively with PKK1 and exhibited the structural and phenotypical characteristics of intermediate and syncytiotrophoblasts. The mean glycogen content of cells cultured in Dulbecco's Modified Eagle's Medium with 5.5 mM glucose was 17.7 +/- 3.2 micrograms/mg protein, remained constant from days 1-4, and was unaltered by higher glucose concentrations (17 and 28 mM) in the medium. Between 2-5 h after a medium change, the cells contained 50% more glycogen than at the time of replacement. Short term (0-5 h) as well as long term incubations (24 h) with both pathological (10(-8) M) and physiological (10(-9) M) concentrations of insulin had no effect, with respect to either the rate of increase in glycogen or the maximum level. We conclude that the glycogen content of isolated syncytiotrophoblasts in vitro is invariant to extracellular glucose concentrations and is not regulated by insulin. This suggests that cells other than syncytiotrophoblasts and their immediate precursors account for the reported alterations of glycogen content in normal human term placenta in vitro under hyperglycemic or hyperinsulinemic conditions.

Interactions between insulin and insulin-like growth factor I in the pathogenesis of polycystic ovarian disease.

Concentrations of growth factors were examined in 28 patients with clinical and endocrinologic signs of polycystic ovarian disease (PCOD). Elevated levels of total insulin-like growth factor I (IGF-I) and decreased levels of the human growth hormone (HGH) were found. Studies of carbohydrate metabolism and of insulin receptors on erythrocytes indicated insulin resistance in all PCOD patients. Elevated insulin and IGF-I levels seem to play a pathogenetic role in PCOD by influencing the development and steroid production of ovarian follicles. Interactions between insulin and IGF-I could be shown at different levels. A positive correlation between elevated insulin and IGF-I concentrations was demonstrated in patients with different classes of gestational diabetes. Hyperinsulinemia seems to be the trigger mechanism and therefore the key to the pathogenetic loop of polycystic ovarian disease.

Serum fructosamine and amniotic fluid insulin levels in patients with gestational diabetes and healthy control subjects.

Gestational diabetic pregnancies with fetal hyperinsulinism should be identified because these cases require insulin therapy. To determine the relationship between the serum fructosamine and amniotic fluid insulin concentrations, these substances were measured in 87 pregnant women with impaired glucose tolerance. Fructosamine was also measured in 678 healthy pregnant control subjects, in 113 of whom amniotic fluid insulin levels were available. Fetal hyperinsulinism was rare at serum fructosamine levels of less than 2.6 mmol/L. These results suggest that when both the oral glucose tolerance test and fructosamine level are used, only 30% of women with gestational diabetes need to undergo amniocentesis to assess fetal insulin homeostasis.