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Med Hypotheses. 1997 Apr;48(4):297-308.

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

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Nutrition 21, San Diego, CA 92109, USA.


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-1 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.

[Indexed for MEDLINE]

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