Insulin-like growth factors

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Space-filling model of IGF-1 based on NMR structure data

Insulin-like growth factor ( English insulin-like growth factors , IGF ) or somatomedins are polypeptides that have a high sequence homology to insulin show and as growth factors act (growth and differentiation of cells). They are formed in the liver cells , but also in other fetal or adult tissues. They are part of a complex system that body cells use to communicate with their environment. This system, which is often referred to as the IGF axis , consists of two membrane receptors (IGF1R and IGF2R), two ligands , a group of six IGF binding proteins (IGFBP 1-6), and some IGFBP-associated proteases .

Functions

Insulin-like growth factor 1 (IGF-1), also called somatomedin C (SM-C), is a growth factor that is structurally very similar to insulin . It is mainly from the liver after stimulation with the from the pituitary derived growth hormone somatotropin secreted . IGF-1 can exert its effect via membrane-bound IGF receptors. These can be detected in almost all tissues and most cell types. It plays a major role in the growth phase of the organism. A gene deletion of the IGF-1 gene has corresponding consequences. Studies have shown that IGF-1 has an influence on the regulation of both physiological and pathological states, especially in cancer development . An influence on cell proliferation and the prevention of apoptosis was described. IGF 1 consists of 70 amino acids in a single chain with three disulfide bridges and has a molar mass of 7.6  kDa . The genetic information of IGF-1 is encoded on chromosome 12 . IGF-1 can also be used to treat degenerative muscle diseases.

Insulin-like growth factor 2 (IGF-2), also called somatomedin A (SM-A), is a growth factor that seems to play an important role in early cell development, i.e. possibly in the fetal phase, while IGF-1 tends to increase is responsible for maximizing growth at a later point in time.

IGF-2 and research into tumor growth

The subtyping of liver tumors based on the special activity of IGF-2 and IFN-regulated genes (see also interferons ) is possible. The involvement of IGF-2 in brain tumors in childhood and in breast cancer is also noteworthy . Chronically elevated serum levels of IGF-2 (as well as IGF-1) could also have a decisive influence on the risk of the development and progression of prostate cancer . The genetic information of IGF-2 is encoded on chromosome 11 .

Use as a doping agent

IGF-1 is often used as a doping agent , for example in bodybuilding . A positive effect on hypertrophy through the supply of IGF-1 in healthy adults is speculative and has not been proven by studies. The Center for Preventive Doping Research at the German Sport University Cologne announced in September 2011 that it had developed a method to detect the synthetic derivatives of IGF-1. The procedure was approved by the World Anti-Doping Agency Wada.

Side effects

The misuse of IGF can cause the following side effects:

  • Limb growth (especially with prolonged, uninterrupted use)
  • Decrease in the secretion of growth hormones
  • Growth of existing tumors
  • Antibody formation

literature

  • Douglas Yee: Insulin-like Growth Factors. IOS Press, Amsterdam 2004 (English).
  • Derek Le Roith: Insulin-like Growth Factors: Molecular and Cellular Aspects. CRC Press, Florida 1991 (English).
  • Isabell Varela-Nieto, Julie Ann Chowen: The growth hormone / insulin-like growth factor axis during development. Springer Science, 2005 (English).
  • GR Adams: The Role of IGF-1 in Muscle Growth and the Potential for Abuse in Athletes. In: British Journal of Sports Medicine , 343, 2000.

Web links

Individual evidence

  1. ↑ PDB  3GF1
  2. ↑ K. Woods et al .: Intrauterine Growth Retardation and Postnatal Growth Failure Associated with Deletion of the Insulin-Like Growth Factor I Gene . In: New England Journal of Medicine , 1996
  3. ↑ ML Slattery, C Sweeney, R Wolff, J Herrick, K Baumgartner, A Giuliano, T. Byers: Genetic variation in IGF1, IGFBP3, IRS1, IRS2 and risk of breast cancer in women living in Southwestern United States . In: Breast Cancer Res Treat , 2007 Aug; 104 (2), pp. 197-209, PMID 17051426
  4. ↑ Y Miura, H Kato, T Noguchi: Effect of dietary proteins on insulin-like growth factor-1 (IGF-1) messenger ribonucleic acid content in rat liver . In: Br. J. Nutr. . 67, No. 2, March 1992, pp. 257-65. PMID 1596498 .
  5. ^ PR Shepherd: Secrets of insulin and IGF-1 regulation of insulin secretion revealed . In: Biochem J . . 377, No. Pt 1, January 2004, pp. E1–2. doi : 10.1042 / BJ20031747 . PMID 14672535 . PMC 1223857 (free full text).
  6. ^ JE Brissenden, A Ullrich, U Francke: Human chromosomal mapping of genes for insulin-like growth factors I and II and epidermal growth factor . In: Nature . 310, No. 5980, 1984, pp. 781-4. PMID 6382023 .
  7. ↑ AA Fallahi et al .: Genetic Doping and Health Damages . In: Iranian J Publ Health , Vol. 40, No. 1, 2011
  8. ↑ T. Nussbaum, S. Vreden, K. Breuhahn, P. Schirmacher: Identification of the insulin-like growth factor (IGF) -II as a therapeutic target structure in hepatocarcinogenesis . In: Z Gastroenterol and Poster Prize of the German Society for Pathology (DGP), DGP annual conference, Wuppertal, 2005
  9. ^ W Hartmann, A Koch, H Brune et al .: Insulin-like growth factor II is involved in the proliferation control of medulloblastoma and its cerebellar precursor cells . In: Am. J. Pathol. . 166, No. 4, April 2005, pp. 1153-1162. PMID 15793295 . PMC 1602379 (free full text).
  10. ↑ S Kalla Singh, QW Tan, C Brito, M De León, C Garberoglio, D. De León: Differential insulin-like growth factor II (IGF-II) expression: A potential role for breast cancer survival disparity, Growth hormone & IGF research . In: Official journal of the Growth Hormone Research Society and the International IGF Research Society , 2010
  11. ↑ Importance of the insulin system for the development of prostate cancer . Mannheim University Hospital
  12. ↑ IGF2. Genetics Home Reference
  13. ↑ L. Tentori et al .: Doping with growth hormone / IGF-1, anabolic steroids or erythropoietin: is there a cancer risk? In: Pharmacological Research , Rome 2007
  14. ↑ CP Velloso: Regulation of muscle mass by growth hormone and IGF-I . PMC 2439518 (free full text)
  15. ↑ The fashion drug IGF-1 can now be detected. In: Welt Online . October 10, 2011, accessed February 21, 2017 .