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

Med Hypotheses. 1997 Apr;48(4):297-308. doi: 10.1016/s0306-9877(97)90098-0.


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.

MeSH terms

  • Aging
  • Animals
  • Arteriosclerosis / etiology
  • Arteriosclerosis / physiopathology
  • Diet, Reducing
  • Energy Intake*
  • Exercise*
  • Gene Expression
  • Humans
  • Hyperplasia
  • Insulin / physiology*
  • Insulin Resistance
  • Insulin-Like Growth Factor Binding Protein 1 / biosynthesis*
  • Liver / metabolism
  • Mitosis
  • Models, Biological
  • Neoplasms / epidemiology
  • Neoplasms / physiopathology
  • Neoplasms / prevention & control*
  • Risk Factors
  • Sex Hormone-Binding Globulin / physiology
  • Stem Cells / cytology
  • Stem Cells / physiology


  • Insulin
  • Insulin-Like Growth Factor Binding Protein 1
  • Sex Hormone-Binding Globulin