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Insulin and GH–IGF-I axis: endocrine pacer or endocrine disruptor?

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Abstract

Growth hormone/insulin-like growth factor (IGF) axis may play a role in maintaining glucose homeostasis in synergism with insulin. IGF-1 can directly stimulate glucose transport into the muscle through either IGF-1 or insulin/IGF-1 hybrid receptors. In severely decompensated diabetes including diabetic ketoacidosis, plasma levels of IGF-1 are low and insulin delivery into the portal system is required to normalize IGF-1 synthesis and bioavailability. Normalization of serum IGF-1 correlated with the improvement of glucose homeostasis during insulin therapy providing evidence for the use of IGF-1 as biomarker of metabolic control in diabetes. Taking apart the inherent mitogenic discussion, diabetes treatment using insulins with high affinity for the IGF-1 receptor may act as an endocrine pacer exerting a cardioprotective effect by restoring the right level of IGF-1 in bloodstream and target tissues, whereas insulins with low affinity for the IGF-1 receptor may lack this positive effect. An excessive and indirect stimulation of IGF-1 receptor due to sustained and chronic hyperinsulinemia over the therapeutic level required to overtake acute/chronic insulin resistance may act as endocrine disruptor as it may possibly increase the cardiovascular risk in the short and medium term and mitogenic/proliferative action in the long term. In conclusion, normal IGF-1 may be hypothesized to be a good marker of appropriate insulin treatment of the subject with diabetes and may integrate and make more robust the message coming from HbA1c in terms of prediction of cardiovascular risk.

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A. Giustina, R. Berardelli, C. Gazzaruso and G. Mazziotti declare that they have no conflict of interest.

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Giustina, A., Berardelli, R., Gazzaruso, C. et al. Insulin and GH–IGF-I axis: endocrine pacer or endocrine disruptor?. Acta Diabetol 52, 433–443 (2015). https://doi.org/10.1007/s00592-014-0635-6

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