Erythrocyte insulin-like growth factor-I receptor evaluation in normal subjects, acromegalics, and growth hormone-deficient and insulin-dependent diabetic children.

Insulin-like growth factor-I (IGF-I) receptors are characterized in several animal and human tissues. IGF-I receptor studies performed in erythrocytes to assess IGF-I receptor status at target-cell tissues are potentially useful for clinical studies, since tissue biopsies or cultures are not required. However, validation of results is challenged by some investigators on the basis of discrepancies described in comparative studies with other cell types, probably related to populations of different cell ages affecting binding to red blood cells (RBCs). By correcting cell age for creatine, we studied IGF-I receptor status in 24 normal subjects (11 adults and 13 children, eight prepubertal and five pubertal) and 33 patients with pathologic conditions (five adult acromegalics, six children with pituitary dwarfism, and 22 type I diabetic children, 15 prepubertal and seven pubertal). Acromegalic patients with higher plasma IGF-I and insulin levels presented lower IGF-I specific binding ([Bo] mean +/- SEM, 6.1% +/- 0.8%) and affinity ([ED50] 28.5 +/- 2.2 ng/mL) than normal adults (Bo, 10.9% +/- 0.7%; ED50, 16.4 +/- 0.9 ng/mL; P < .001), and growth hormone (GH)-deficient children showed higher IGF-I binding 24.6% +/- 1.7%, P < .001) without significant affinity alterations than normal prepubertal children (Bo, 14.7% +/- 1.0%). Both prepubertal and pubertal type I diabetic children with higher GH levels presented decreased IGF-I binding (11.4% +/- 0.9% for prepubertal, P < .05; 10.0% +/- 1.1% for pubertal, P < .05) to RBC receptors in comparison to the respective control group (14.7% +/- 10% and 14.9% +/- 1.3%, prepubertal and pubertal, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Computed tomography and ultrasonography of the adrenal glands in paracoccidioidomycosis. Comparison with cortisol and aldosterone responses to ACTH stimulation.

Fifteen patients with proven disseminated paracoccidioidomycosis (PCM) had computed tomography (CT) and ultrasonography (US) performed to evaluate the form, shape, density and size of their adrenal glands. Plasma and urinary cortisol were determined and adrenal reserve assessed by measuring the cortisol and aldosterone responses to synthetic ACTH. The adrenal CT showed unilateral lesions in two cases and bilateral in another four. The US study showed more frequent alterations, unilateral in seven and bilateral in three subjects. Combining both methods increased the sensitivity to 85% of the cases. All patients had normal plasma cortisol concentrations and normal or increased urinary cortisol excretion. Plasma aldosterone concentration was also normal except in one patient with hypokalemia. Seven patients showed diminished cortisol responses, five had subnormal aldosterone responses and in five plasma aldosterone concentration increased more than normally after stimulation by ACTH. There was an incidence of limited adrenal reserve in 53% of the patients on ACTH stimulation. No correlation was evident between the disorders in adrenal steroid responses to ACTH and changes in morphology revealed by CT and/or US.

Insulin resistance in acromegaly: evaluation by studies of insulin binding to erythrocytes.

Insulin binding to erythrocytes (RBC) was evaluated in 10 acromegalic patients (6 females and 4 males) in comparison to 22 normal subjects (12 females and 10 males) in an attempt to study the insulin resistance of acromegaly. Basal glucose from all acromegalic patients were within the normal range but incremental glucose and insulin curves, respectively, on oGTT were significantly increased in the acromegalic patients suggesting an insulin resistant state. Basal growth hormone concentrations were elevated in all acromegalic patients, but no correlation was observed between insulin and GH levels. The insulin binding studies in the acromegalic patients showed a decreased binding due to a reduction in the receptor number per cell but with no alterations in the affinity state. Correction of data for creatine, as a procedure of normalization of binding data for a standardized RBC cell age, enhanced the reduction of insulin binding of the acromegalic patients in comparison to controls in consequence to the younger population of acromegalic RBC as indicated by their increased creatine concentrations. In conclusion, the insulin resistant state in acromegalics observed in our study is accompanied by a decrease in the insulin binding to the RBC receptor due to a reduction of the receptor concentration as mediated by the compensatory hyperinsulinemia.

Erythrocyte insulin receptor: normalization of binding data for the average cell age by the red cell creatine determination in obese, diabetic and acromegalic patients.

Insulin binding studies performed in erythrocytes (RBC) have been employed in clinical studies assessing the status of insulin receptors at target cell tissues. However, some authors challenged this assumption on the basis of some discrepancies described in comparative studies of other cell types, probably related to populations of different cell age affecting insulin binding to RBC. We evaluated insulin binding to RBC in normal males (n = 10), non-obese diabetic males (n = 13), normal females (n = 15), obese (n = 11) and acromegalic females (n = 5), before and after correction of insulin binding data for creatine concentration in the RBC as a procedure of correction for age, since a negative correlation was described between creatine content and RBC age which also correlates inversely with % insulin binding. Insulin binding in all three groups of patients was not statistically different from corresponding values for normal males and females respectively before correction of data for creatine, but significantly reduced values were found after adjustment for creatine in accordance with published data concerning monocytes. In conclusions, the procedure of correcting insulin binding in erythrocytes by the creatine content in RBC is potentially useful for clinical investigations, since the influence of RBC age is excluded.

Effect of short- and long-term chlorpropamide therapy on oral glucose tolerance and erythrocyte insulin receptors in non-obese non-insulin dependent diabetes mellitus.

Erythrocyte (RBC) insulin receptors and the insulin response to glucose load (oGTT) were evaluated in ten male, non-obese, non-insulin dependent diabetic patients (NIDDM) before and after 14 and 90 days of 250 mg/day of chlorpropamide administration. In addition, as a control group, twelve healthy non-obese subjects were studied. Diabetic patients with fasting plasma glucose level higher than 14 mmol/l (group A), presented a significant improvement in the incremental glucose area only after 90 days of therapy. There was an evident reduction in insulin secretion, in comparison to normals, which however increased progressively during drug administration. No alterations in insulin binding to RBC receptors were observed either before or after the use of chlorpropamide, but the normalization of the initially low number of receptors per cell (N) and an increased high affinity constant (Ke) were achieved. In group B with fasting glucose less than 14 mmol/l there was a significant reduction in plasma glucose levels during oGTT without changes in glucose areas and a significant improvement of the insulin secretion was noted only in the early samples. Except for transient alterations in N and Ke no significant changes were observed in insulin-RBC binding parameters. We conclude that the improvement in the glucose tolerance in NIDDM is associated both to a greater insulin secretion and to the correction of the alterations in receptor parameters which could be related, at least partially, to proportionate changes in reticulocyte count.

Sequential studies of glucose tolerance and red blood cell insulin receptors in normal human pregnancy.

Insulin binding to erythrocytes was sequentially studied in 12 healthy pregnant women during the anabolic (11-22 wk) and the catabolic (31-38 wk) gestational phases. For comparison, we studied 12 nonpregnant subjects at mid-luteal and mid-follicular menstrual phases. Oral glucose tolerance tests were also performed during these studies. There was a progressive worsening of the glucose tolerance from the anabolic to the catabolic phase associated with fasting hypoglycemia and hyperinsulinemia. The worsening of glucose tolerance was accompanied by a progressive increment of insulin secretion. Insulin binding to red blood cells increased progressively from the anabolic to the catabolic phase, due to an increased number of receptors per cell, associated with a reduction in the apparent affinity at the low occupancy levels. We concluded that the insulin resistance of pregnancy was not accompanied by an impaired binding of insulin to its receptors, at least in the RBC. The data suggest that the defect of insulin action lies at a site distal to the receptor.

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.