Coupling of insulin‐responsive glucose transport to receptors for insulin‐like growth factor 1 in primary human fibroblasts
- 1 June 1990
- journal article
- research article
- Published by Wiley in European Journal of Biochemistry
- Vol. 190 (3), 553-557
- https://doi.org/10.1111/j.1432-1033.1990.tb15609.x
Abstract
We have recently described an insulin-resistant patient with leprechaunism (leprechaun G.) having a homozygous leucine .fwdarw. proline mutation at amino acid position 233 in the .alpha.-chain of the insulin receptor. The mutation results in a loss of insulin binding to cultured fibroblasts. Fibroblasts from the patient and control individuals were used to quantify the stimulation of 2-deoxyglucose uptake by insulin and insulin-like growth factor 1 (IGF-1). Insulin hardly stimulates basal 2-deoxyglucose uptake in the patient''s fibroblasts whereas in control fibroblasts the uptake of 2-deoxyglucose is stimulated by insulin approximately 1.7 times. In contrast, IGF-1 stimulates hexose uptake in the patient''s fibroblasts 1.8 times, a similar value to that obtained by stimulation of control fibroblasts with insulin or IGF-1. With both types of fibroblasts, maximal IGF-1 response is reached at about 10 nM IGF-1, the ED50 being approximately 4 nM. The results indicate that the insulin responsive glucose transport in primary fibroblasts is functionally linked to the receptor for IGF-1. Insulin binds with an approximately 200-fold lower affinity to IGF-1 receptors, compared to homologous IGF-1 binding. As an insulin concentration of 10 .mu.M is unable to give maximal stimulation of glucose uptake in the patient''s fibroblasts, which is already seen with 10 nM IGF-1, it seems that occupation of IGF-1 receptors by insulin on the patient''s cells is less efficient at stimulating hexose uptake compared to homologous activation.This publication has 18 references indexed in Scilit:
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