| Homepage | Imprint |
|
||
 |
Insulin-like growth factorThe insulin-like growth factors (IGFs) are polypeptideswith high sequence similarityto insulin. IGFs are part of a complex system that cells use to communicate with their physiologic enviornment. This complex system (often referred to as the IGF "axis) consists of two cell-surface receptors (IGF1R and IGF2R), two ligands (IGF-I and IGF-II), a family of six high-affinity IGF binding proteins (IGFBP 1-6), as well as associated IGFBP degrading enzymes, referred to collectivly as proteases. This system is important for both the regulation of normal physiology, as well as a number of pathological states, including cancer. The IGF axis has been shown to play roles in the promotion of cell proliferation and the inhibition of cell death (apoptosis). IGF-II is thought to be a primary growth factorrequired for early development while IGF-I expression is seen in later life. Gene knockoutstudies in mice have confirmed this though other animals are likely to regulate the expression of these genes in distinct ways. While IGF-2 maybe primarily fetalin action it is also essential for development and function of organs such as the brain, liverand 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 cellin 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 growthand development, especially in nerve cells, as well as cellular DNAsynthesis. IGF-II is secreted by the brain, kidney, pancreasand 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). There is currently significant data suggesting that IGFBPs play important roles in additon to their ability to regulate IGFs. Studies of recent interest show that the IGF axis play an important role in aging. Nematodes, fruit-fliesand 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 evolutionaryorigin. Other studies are beginning to uncover the important role the IGFs play in diseases such as cancerand 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 receptorsused 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 also
References
ja:??????????
|
