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  1. Up-regulation of IGF binding protein-1 as an anticarcinogenic strategy : relevance to caloric restriction, exercise, and insulin sensitivity.

    Article - En anglais

    The mitotic rate of stem cells is a major determinant of cancer risk.

    Insulin-like growth factors (IGFs) are virtually obligate stimulants of cell turnover in nearly every tissue.

    IGF activity is subject to rapid modulation by hepatic release of IGF binding protein-1 (IGFBP-1), a factor whose synthesis is suppressed by insulin and increased by glucagon.

    Up-regulation of IGFBP-1 production can be expected to decrease IGF activity and thereby diminish cancer risk.

    Measures that sensitize peripheral tissues to insulin, and thereby down-regulate insulin secretion, can be expected to increase IGFBP-1 synthesis, provided that they do not unduly sensitize hepatocytes as well.

    Prolonged aerobic exercise and caloric restriction also increase IGFBP-1 production.

    Since IGF-I suppresses hepatic synthesis of sex hormone binding globulin (SHBG), down-regulation of IGF activity will increase SHBG levels and thus diminish the availability of free sex hormones - an effect that should further decrease cancer risk in sex hormone-responsive tissues.

    These considerations rationalize many findings in animal and epidemiologic studies, and suggest that non-diabetic insulin resistance may be a significant cancer risk factor.

    Increased IGF activity associated with insulin resistance may also promote benign hyperplasias - most notably atherosclerosis.

    Hyperinsulinemia stimulates intimal hyperplasia indirectly, via IGF.

    Mots-clés Pascal : Carcinogenèse, Prévention, Régulation, Facteur croissance IGF, Exercice physique, Bilan calorique, Restriction modification, Epidémiologie, Modèle animal, Article synthèse, Tumeur maligne, Activité biologique

    Mots-clés Pascal anglais : Carcinogenesis, Prevention, Regulation(control), Insulin like growth factor, Physical exercise, Caloric balance, Restriction modification, Epidemiology, Animal model, Review, Malignant tumor, Biological activity

    Logo du centre Notice produite par :
    Inist-CNRS - Institut de l'Information Scientifique et Technique

    Cote : 97-0320449

    Code Inist : 002B04E05. Création : 12/09/1997.