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Decrease in insulin and insulin-like growth factor I (IGF-I) binding to erythrocytes from patients with cystic
1Laboratoire de Physiologie, Biologie de la Reproduction et du Développement, CHRU, Clermont-Ferrand, France.
Diabetes & Metabolism
|March 13, 1998
Summary
Cystic fibrosis patients show reduced insulin and insulin-like growth factor I (IGF-I) binding to erythrocytes, linked to growth failure and potential glucose intolerance. This suggests receptor defects contribute to metabolic issues in cystic fibrosis.
Area of Science:
- Endocrinology
- Genetics
- Metabolic Disorders
Background:
- Cystic fibrosis (CF) is an autosomal recessive disease impacting exocrine glands, often leading to undernutrition, growth retardation, and glucose intolerance.
- Understanding defects in insulin and insulin-like growth factor I (IGF-I) receptor function is crucial for explaining these metabolic complications.
Purpose of the Study:
- To investigate and define defects in insulin and IGF-I receptor binding in erythrocytes of cystic fibrosis patients.
- To correlate hormone receptor binding alterations with clinical manifestations like growth failure.
Main Methods:
- 125I-insulin and 125I-IGF-I binding assays were performed on erythrocytes from cystic fibrosis patients (n=23) and controls (n=13).
- Erythrocytes were isolated using Ficoll-Hypaque gradient centrifugation.
- Hormone binding was analyzed in cell suspensions, assessing binding capacity and affinity constants.
Main Results:
- Cystic fibrosis patients exhibited a significant decrease in insulin (33%) and IGF-I (40%) binding compared to controls.
- These reductions were primarily due to a ~50% decrease in the binding capacity of high-affinity receptors.
- Insulin binding reduction correlated with the degree of growth failure, and 50-60% of patients showed altered binding parameters.
Conclusions:
- Reduced insulin and IGF-I binding in cystic fibrosis patients, particularly affecting high-affinity receptors, may contribute to insulin resistance and glucose abnormalities.
- These receptor binding alterations, especially when correlated with growth failure, offer insights into the pathogenesis of metabolic dysfunction in undernourished cystic fibrosis patients.