Up-regulation of IGF binding protein-1 as an anticarcinogenic strategy: relevance to caloric restriction, exercise, and insulin sensitivity.
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.
McCarty
M F
MF
Nutrition 21, San Diego, CA 92109, USA.
D000375:Aging; D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology / Q000503:physiopathology; D004038:Diet, Reducing; D002149:Energy Intake; D015444:Exercise; D015870:Gene Expression; D006801:Humans; D006965:Hyperplasia; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism; D008938:Mitosis; D008954:Models, Biological; D009369:Neoplasms / Q000453:epidemiology / Q000503:physiopathology / Q000517:prevention & control*; D012307:Risk Factors; D012738:Sex Hormone-Binding Globulin / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D012738:Sex Hormone-Binding Globulin