title: Insulin and GH-IGF-I axis: endocrine pacer or endocrine disruptor?
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.
authors.affiliation: Chair of Endocrinology and Metabolism, University of Brescia - A.O. Spedali Civili di Brescia, 25123, Brescia, Italy, a.giustina@libero.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Giustina
authors.forename: R
authors.initials: R
authors.lastname: Berardelli
authors.forename: C
authors.initials: C
authors.lastname: Gazzaruso
authors.forename: G
authors.initials: G
authors.lastname: Mazziotti
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy*; D052244:Endocrine Disruptors / Q000097:blood*; D013006:Growth Hormone / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000627:therapeutic use*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000378:metabolism
chemical_list: D015415:Biomarkers; D052244:Endocrine Disruptors; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D017526:Receptor, IGF Type 1