Comparison of insulin antibody levels during the first 3 years of treatment of adult diabetics with monocomponent porcine lente-insulin and single peak beef NPH insulin.

Insulin antibody production was studied in two groups of 9 adult diabetics each, who were never treated before with insulin. One group received Monocomponent porcine lente insulin (MC) and the other group single peak beef NPH insulin, for 3 years. Insulin antibodies were evaluated by antibody-bound immunoreactive insulin (Abl) and by the labelled insulin binding capacity (IBC) which presented a significant correlation best fitted by a logarithmic curve. The patients treated with MC insulin developed significant levels of insulin antibodies, however, at lower levels and appearing later in comparison to those with beef NPH. Only 3 patients did not produce significant levels of insulin antibodies. The highest titers occurred after different lengths of treatment in the two groups of patients. Abl decreased after continuation of treatment particularly in the MC series. While in the MC-treated patients there was some positive correlation between the insulin dose and the level of Abl no significant correlation was found between the diabetes control and insulin antibody titers in both groups of patients.

Insulin resistance in Cushing's disease. Evaluation by studies of insulin binding to erythrocytes.

Studies of 125I -insulin binding to erythrocytes (RBC) from 5 patients with Cushing's disease were performed in an attempt to evaluate the insulin resistance in this disease. Five obese, nondiabetic patients and six normal subjects served as controls. Insulin resistance was present in both the obese, nondiabetic subjects and in the patients with Cushing's disease. Patients with Cushing's disease showed insulin resistance out of proportion to obesity, and of greater severity than in the obese subjects. As in previous studies, the insulin resistance of the obese subjects could be at least partially ascribed to a reduced number of receptors. In contrast, in our patients with Cushing's disease, no physiologically significant changes in the parameters of insulin-receptor interaction could be demonstrated. This suggests that the RBC insulin receptor is not involved in this type of insulin resistance.

Human erythrocyte insulin receptors in normal male and female subjects.

Human red blood cells (RBC) have been shown to have highly specific insulin receptors. We have studied the binding characteristics of insulin to these receptors in erythrocytes from normal male and female subjects on their usual diet and physical activity. There were no significant differences in insulin binding in erythrocytes from females between the two phases of the menstrual cycle. However, the receptor concentration was higher in the 2nd half of the cycle accompanied by a reduction in affinity. Binding curves of 125-I-insulin to RBC from males were higher than females in either phases of the menstrual cycle, primarily due to an increase in receptor concentration when compared to females in the follicular phase and mediated by an increased affinity at low receptor occupancy when compared to females in the luteal phase. We speculated that the differences in the binding characteristics of 125I-insulin to RBC insulin receptors are mediated by differences in the levels of sex hormones.

Residual beta-cell function in type II diabetes and evaluation of the hepatic insulin extraction.

Insulin and C-peptide (free insulin and C-peptide in insulin-treated patients) were measured after glucose stimulation in nine Type II diabetics on chlorpropamide, eleven insulin-treated maturity-onset diabetics and in 8 normal controls. Dissociation between C-peptide and insulin response to glucose was observed in several diabetics. The relation between incremental molar areas under C-peptide and insulin curves, after glucose challenge (delta CPR - delta IRI/delta CPR) were used to evaluate the hepatic insulin extraction in all but the insulin-treated diabetics. The lower insulin requirements and better control of the short-duration insulin-treated maturity-onset diabetics in relation to the long-term ones could not be explained either by the residual insulin secretion or by the level of "insulin antibodies". The chlorpropamide-responsive patients presented higher insulin levels after the glucose challenge and a lower hepatic insulin extraction than the non-responsive ones.

Avaliacao e padronizacao de metodo para determinacao de niveis de insulina total e livre em plasma contendo anticorpos antiinsulina. / Evaluation and standartization of a method for measuring free and total insulin in plasma containing antibodies to insulin

Os autores descrevem um metodo simplificado para medir insulina livre, total e ligada ao anticorpo em pacientes tratados com insulina e que apresentam anticorpos anti-insulinicos. A insulina livre, metabolicamente ativa, e extraida do plasma com polietileno-glicol a 25%. A insulina total e extraida com a solucao de polietileno-glicol apos a dissociacao do complexo antigeno-anticorpo com HCI diluido. Aliquotas dos extratos sao usadas no sistema de radioimunoensaio. A insulina ligada ao anticorpo e a diferenca entre os valores de insulina total e livre e reflete a concentracao dos anticorpos insulinicos presentes. Determinou-se tambem a capacidade insulino-ligante do plasma, apos sua incubacao com radioinsulina e que se correlacionou significativamente com a insulina total nos pacientes com anticorpos antiinsulina. Os niveis de insulina livre medidos nos pacientes com anticorpos foram similares aos observados nos controles normais, independentemente dos valores da insulina total

Preparation of high-quality iodine-125-labelled pituitary luteinizing hormone for radioimmunoassay.

High quality pituitary luteinizing hormone labelled with 125-I was obtained after separating out the more heavily iodinated fractions, through starch gel electrophoresis, using the cathodal component (Fraction 1) which was further purified on Sephadex G-100, giving an almost pure 125-I-labelled luteinizing hormone preparation, presenting excellent immunoreactivity and low levels of damage on incubation in plasma. The quality control of the steps of the technique was done with plasma-coated talc (200 mg) which compared favorably, as far as being an indication of intact labelled luteinizing hormone, with the more time-consuming chromatoelectrophoresis.