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Increased expression of low-affinity insulin receptor isoform and insulin/insulin-like growth factor-I hybrid receptors in term placenta from insulin-resistant women with gestational hypertension

Summary

Gestational hypertension is associated with insulin-resistance; insulin and insulin-like growth factor-1 (IGF-1), acting through their receptors, play a role in the growth of the feto-placental unit. Since both receptors are exposed to the maternal circulation, it has been suggested that maternal metabolic abnormalities might affect placental insulin (HIR) and IGF-1 (IGF-1R) receptors. To clarify this issue, we characterized HIR and IGF-1R in placenta at term from normal women, normoinsulinaemic women with gestational hypertension (NGH), and hyperinsulinaemic women with gestational hypertension (HGH). Insulin binding was decreased in HGH women (B/T 0.12±0.03) compared to control and NGH women (B/T 0.18±0.07, p<0.036; and 0.22±0.5, p<0.009 respectively). Receptor affinity was lower in HGH women (ED50 0.95±0.32 nmol/l) than control and NGH women (ED50 0.42±0.19 nmol/l, p<0.01; and 0.40±0.1 nmol/l, p<0.007, respectively), whereas low-affinity Ex11+ isoform was higher in HGH women (Ex11+ 50±7,%) than in control and NGH women (Ex11+ 34±9%, p<0.001; and 39±4%, p<0.01, respectively). Increased expression of Ex11+ isoform was correlated with ED50 (r=0.71; p<0.002) and insulinaemia (r=0.70, p<0.002). IGF-I binding was increased in HGH women (B/T 0.17±0.03) compared to control and NGH women (B/T 0.09±0.05, p<0.002; and 0.11±0.03, p<0.002, respectively). IGF-IR affinity was similar in the three groups. The percentage of insulin/IGF-I hybrid receptors was increased in HGH women (85±3%) compared to control and NGH women (68±7%, p<0.001; and 63±9%, p<0.001, respectively), and was positively correlated with insulinaemia (r=0.62, p<0.018), ED50 of insulin binding (r=0.62, p<0.05), and maximal IGF-I binding (r=0.69, p<0.004); whereas it was inversely correlated with maximal insulin binding (r=−0.69, p<0.004). Results provide the first evidence for altered expression of insulin/IGF-I hybrids found in insulin-resistance states.

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Abbreviations

IGF-1:

Insulin-like growth factor-1

IGF-1R:

IGF-1 receptor

HIR:

human insulin receptor

OGTT:

oral glucose tolerance test

HGH:

hyperinsulinaemia with gestational hypertension

NGH:

normoinsulinaemia with gestational hypertension

PA-C:

polyclonal antibody C

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Drs. H. Valensise, Y. Y. Liu, M. Federici have contributed equally to this work

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Valensise, H., Liu, Y.Y., Federici, M. et al. Increased expression of low-affinity insulin receptor isoform and insulin/insulin-like growth factor-I hybrid receptors in term placenta from insulin-resistant women with gestational hypertension. Diabetologia 39, 952 (1996). https://doi.org/10.1007/BF00403915

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Keywords

  • Insulin receptor
  • IGF-I receptor
  • hybrid receptor
  • insulin resistance
  • gestational hypertension
  • placenta