Insulin-like growth factor

The insulin-like growth factors (IGFs) are polypeptides with high sequence similarity to insulin. They can trigger the same cellular responses as insulin, including mitogenesis in cell culture. IGF-II is thought to be a primary growth factor required for early development while IGF-I expression is seen in later life. Gene knockout studies in mice have confirmed this though other animals are likely to regulate the expression of these genes in distinct ways. While IGF-2 may be primarily fetal in action it is also essential for development and function of organs such as the brain, liver and kidney.

Insulin-like growth factor 1 (IGF-1) is mainly secreted by the liver as a result of stimulation by growth hormone (hGH). Almost every cell in the human body is affected by IGF-1, especially cells in muscle, cartilage, bone, liver, kidney, nerves, skin, and lungs. In addition to the insulin-like effects, IGF-1 can also regulate cell growth and development, especially in nerve cells, as well as cellular DNA synthesis.

IGF-II is secreted by the brain, kidney, pancreas and muscle in mammals. It is more specific in action than IGF-1. In adult humans it is found at 600 times the concentration of insulin.

IGF-1 and IGF-II are regulated by a family of genes known as the IGF-Binding Proteins. These proteins help to modulate IGF action in complex ways that involve both inhibiting IGF action by preventing binding to the IGF-1 receptor as well as promoting IGF action possibly through aiding in delivery to the receptor and increasing IGF half-life. Currently, there are 6 characterized IGF Binding Proteins (IGFBP1-6). While non IGF-mediating functions have been proposed for many of these proteins, conclusive evidence has yet to be shown.

Studies of recent interest show that the IGF axis play an important role in aging. Nematodes, fruit-flies and other organisms have an increased life span when the gene equivalent to the mammalian IGF is knocked out. Clearly the IGF/Insulin axis has an ancient evolutionary origin. Other studies are beginning to uncover the important role the IGFs play in diseases such as cancer and diabetes, showing for instance that IGF-1 stimulates growth of both prostate and breast cancer cells. ^1-3 Researchers are not in complete agreement about the degree of cancer risk that IGF-1 poses.

Further work is required to determine the main receptors used by these growth factors to elicit their effects. Currently the IGF's are known to bind the insulin receptor, IGF-1 receptor, IGF-2 receptor, the insulin-related receptor and possible other receptors. IGF-1 and IGF-2 strongly bind to and activate the IGF-1 receptor, with weaker binding and action occurring through insulin receptors. The IGF-2 receptor only binds IGF-2 and acts as a "clearance receptor" - it activates no intracellular signalling pathways, functioning only as an IGF-2 sequestering agent and preventing IGF-2 signalling.

IGF-1 is present in milk, especially when the cow has been treated with bovine growth hormone.

See insulin-like growth factor 1.

References

1. Cohen, Pinchas, et al. "Insulin-like growth factors (IGFs), IGF receptors, and IGF-binding proteins in primary cultures of prostate epithelial cells". Journal of Clinical Endocrinology and Metabolism, Vol. 73, No. 2, 1991, pp. 401-07

2. Lippman, Marc E. "The development of biological therapies for breast cancer". Science, Vol. 259, January 29, 1993, pp. 631-32

3. Papa, Vincenzo, et al. "Insulin-like growth factor-I receptors are overexpressed and predict a low risk in human breast cancer". Cancer Research, Vol. 53, 1993, pp. 3736-40