Abstract
Insulin-like growth factor I (IGF-I) is a polypeptide hormone produced mainly by the liver in response to the endocrine GH stimulus, but it is also secreted by multiple tissues for autocrine/paracrine purposes. IGF-I is partly responsible for systemic GH activities although it possesses a wide number of own properties (anabolic, antioxidant, anti-inflammatory and cytoprotective actions).IGF-I is a closely regulated hormone. Consequently, its logical therapeutical applications seems to be limited to restore physiological circulating levels in order to recover the clinical consequences of IGF-I deficiency, conditions where, despite continuous discrepancies, IGF-I treatment has never been related to oncogenesis. Currently the best characterized conditions of IGF-I deficiency are Laron Syndrome, in children; liver cirrhosis, in adults; aging including age-related-cardiovascular and neurological diseases; and more recently, intrauterine growth restriction.The aim of this review is to summarize the increasing list of roles of IGF-I, both in physiological and pathological conditions, underlying that its potential therapeutical options seem to be limited to those proven states of local or systemic IGF-I deficiency as a replacement treatment, rather than increasing its level upper the normal range.
Highlights
Insulin-like growth factor I (IGF-I) is a 70 aa polypeptide hormone with endocrine, paracrine, and autocrine effects
Children with Intrauterine growth restriction (IUGR) show an impaired growth hormone (GH)/IGF-I axis, which might be contributing to reduced insulin sensitivity and IGF-I resistance, as higher basal and GH-induced IGF-I levels are required to achieve a growth velocity similar to that of other children, what secondarily leads to a compensatory hyperinsulinemia to counteract insulin antagonistic effects of GH [195] and, an impaired regulation of glucose transporter-4 expression by insulin in muscle and adipose tissue [196]
We have previously shown that IGF-I is a main character in restoring mitochondrial dysfunction during aging by increasing mitochondrial membrane potential, reducing oxygen consumption, and increasing ATP synthesis what in turn minimize the ccytochrome release to the cytoplasm and subsequently promote neural survival by decreasing caspase-induced apoptosis [55,56], in agreement with in vitro reported
Summary
Insulin-like growth factor I (IGF-I) is a 70 aa polypeptide hormone with endocrine, paracrine, and autocrine effects. Children with IUGR show an impaired GH/IGF-I axis, which might be contributing to reduced insulin sensitivity and IGF-I resistance, as higher basal and GH-induced IGF-I levels are required to achieve a growth velocity similar to that of other children, what secondarily leads to a compensatory hyperinsulinemia to counteract insulin antagonistic effects of GH [195] and, an impaired regulation of glucose transporter-4 expression by insulin in muscle and adipose tissue [196] In another hand, fetal responses to IUGR-related hypoxia include downregulation of insulin, IGF-I, and IGF-II and increased expression of inhibitory IGFBPs. Hypoxia activates the hypothalamo-pituitary-adrenal (HPA). We have previously shown that IGF-I is a main character in restoring mitochondrial dysfunction during aging by increasing mitochondrial membrane potential, reducing oxygen consumption, and increasing ATP synthesis what in turn minimize the ccytochrome release to the cytoplasm and subsequently promote neural survival by decreasing caspase-induced apoptosis [55,56], in agreement with in vitro reported
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