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Increased insulin receptor binding in erythrocytes from growth hormone-deficient children
N Dávila1, B Barceló, M C Carranza
1Servicio de Endocrinología, Universidad Autónoma de Madrid, Spain.
Insights
Children with growth hormone deficiency (GHd) exhibit increased insulin binding to erythrocytes, despite normal insulin sensitivity. This suggests altered insulin receptor dynamics in GH deficiency, impacting glucose metabolism.
Area of Science:
- Endocrinology
- Metabolic Research
- Pediatric Endocrinology
Background:
- Growth hormone (GH) plays a crucial role in metabolic regulation.
- Insulin resistance is often associated with GH deficiency, but its precise mechanisms require further investigation.
- Erythrocyte insulin binding can serve as a model for studying insulin receptor function.
Purpose of the Study:
- To investigate insulin binding characteristics to erythrocytes in children with growth hormone deficiency (GHd).
- To compare insulin receptor parameters between GHd children and healthy controls.
- To explore the relationship between altered insulin binding and insulin sensitivity in GHd.
Main Methods:
- Erythrocytes were isolated from GHd children (n=10) and control children (n=11).
- Insulin binding assays were performed at varying unlabeled insulin concentrations.
- Scatchard analysis using a two-site model was employed to determine receptor concentration (R1, R2) and dissociation constants (KD1, KD2).
Main Results:
- Erythrocytes from GHd children showed significantly increased insulin binding at low insulin concentrations compared to controls.
- A threefold decrease in apparent receptor affinity was observed in GHd children.
- Scatchard analysis revealed significantly higher R1 and KD1 for high-affinity sites in GHd erythrocytes, while low-affinity sites remained unchanged.
- Insulin sensitivity and glucose tolerance were normal in the GHd group.
Conclusions:
- Children with GH deficiency exhibit altered insulin receptor characteristics on erythrocytes, specifically increased high-affinity receptor concentration and decreased affinity.
- Despite these receptor changes, normal insulin sensitivity and glucose tolerance were maintained in the studied GHd cohort.
- The findings suggest a complex interplay between growth hormone, insulin signaling, and glucose homeostasis that warrants further research.
Abstract:
Erythrocytes from growth hormone-deficient children (GHd-children) (n = 10) showed a statistically significant increase in insulin binding at low unlabeled insulin concentrations, together with a threefold decrease in apparent receptor affinity, as compared to control children (C) (n = 11). Scatchard analysis of the binding data using the two-site model revealed that both the receptor concentration R1 [GHd-children 0.10 +/- 0.01 ng/ml and C 0.03 +/- 0.002 ng/ml] and the dissociation constant KD1 [GHd-children (0.48 +/- 0.05) x 10(-9) M and C (0.19 +/- 0.01) x 10(-9) M] for high affinity-low capacity sites were significantly increased in erythrocytes from GHd-children, while neither receptor concentrations (R2) nor the dissociation constant (KD2) for low affinity-high capacity sites proved to be altered. These events were accompanied by a normal sensitivity to insulin as well as glucose tolerance in the GHd-group. The meaning of the increased insulin binding with normal insulin sensitivity in GH-deficiency is discussed.