Growth Factors IGFs

Site of production j3-cell, pancreatic islet Many sites Many sites 

Major source of circulating form /3-cell, pancreatic islet Liver Liver 

Regulation of secretion Glucose, amino acids, catecholamines GH, insulin, nutritional status GH 

Binding proteins in serum None 3 (types 1,3,4) 6 (types 1-6) 

Target tissues Liver, muscles, adipose, skin. Muscles, connective tissue. Muscles, connective tissue. 

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Insulin and Amylin. Insulin is a member of a family of related peptides, the insulin-like growth factors (IGFs), including IGF-I and IGF-II (60) and amylin (75), a 37-amino acid peptide that mimics the secretory pattern of insulin. Amylin is deficient ia type 1 diabetes meUitus but is elevated ia hyperinsulinemic states such as insulin resistance, mild glucose iatolerance, and hypertension (33). Insulin is synthesized ia pancreatic P cells from proinsulin, giving rise to the two peptide chains, 4. and B, of the insulin molecule. IGF-I and IGF-II have stmctures that are homologous to that of proinsulin (see INSULIN AND OTHER ANTIDIABETIC DRUGS). 

Somatomedins are polypeptide mediators produced in response to growth hormone in the liver, e.g. insulinlike growth factors (IGFs). In particular, IGF-1 is the main mediator of growth hormone action. 

Other tissues/cells Inhibition of growth factor (IGF 1, EGF, PDGF)and cytokine (IL6, IFN-y) secretion... 

There is only one major system of interacting growth factors and receptors in the fetus — the insulin (INS) and insulin-like growth factor (IGF) system (Table 1 and Fig. 1). Ignoring various binding proteins that modulate IGF actions in tissues and... 

Raff Not necessarily. In poodles, for example, differences in size between miniatures, toys and regulars apparently mirror levels of insulin-like growth factors (IGFs). To me that is not especially interesting. We know that if you put in more growth hormone (GH) or IGF, you get a proportionally bigger animal. What interests me more is how a few hundred cells in a limb primordium know what the approximate final size of the limb should be. This seems to me to be a more fundamental question than how growth hormones adjust the final size of an animal. 

There are several alternative pathways associated with the balance between proliferation and apoptosis that are affected by lycopene treatment, especially the insulin-like growth factor (IGF) signaling pathway. Another is the possibility that lycopene or one of its breakdown products has retinoid activity. Kotake-Nara et al. compared acyclo-retinoic acid, an in vitro oxidation product of lycopene, to four actively researched anticarcinogenic retinoids. Acycloretinoic acid was found to more actively reduce PC-3 and DU-145 cell viabilities (but not LNCaP) through apoptosis in a medium already containing small amounts of natural retinoids. But study concentrations were 20 pM, far above physiologically relevant lycopene concentrations, let alone the smaller concentration of one of its breakdown products. Acycloretinoic acid had a very low affinity for the retinoid X receptors (RXR) and retinoic acid receptors (RAR) receptors (Kotake-Nara et al. 2002). 

Riso, P, A Brusamolino, A Martinetti, and M Porrini. 2006. Effect of a tomoto drink intervention on insulin-like growth factor (IGF)-l serum levels in health subjects. Nutr Cancer 55(2) 157-162. 

Voskuil, DW, A Vrieling, CM Korse et al. 2008. Effects of lycopene on the insulin-like growth factor (IGF) system in premenopausal breast cancer surviviors and women at high familial breast cancer risk. Nutr Cancer 60(3) 342-353. 

Horney, M.J. et al. (2001) Synthesis and characterization of insulin-like growth factor (IGF)-l photoprobes selective for the IgG-binding proteins (IGFBPs) photoaffinity labeling of the IGF-binding domain on IGFBP-2./. Biol. Chem. 276(4), 2880-2889. 

Insulin like growth factor IGF-1 tml/tmA Prrn PpsbAfPpsbA 33% Daniell... 

The presence of serum-binding proteins. Some biopharmaceuticals (including insulin-like growth factor (IGF), GH and certain cytokines) are notable in that the blood contains proteins that specifically bind them. Such binding proteins can function naturally as transporters or activators, and binding can affect characteristics such as serum elimination rates. 

As indicated in the discussion of axotomy models, the beneficial influences of trophic factors on motor neurons provide potential therapeutic opportunities. Although previous human trials have been disappointing (for review see [111,112]), adenoassociated viral (AAv) delivery of insulinlike growth factor (IGF)-l to muscle prolongs survival in mutant SOD1 mice [111]. Thus, following intramuscular injection, the retrograde transport of AAV-IGF-1 appears to provide trophic influences to motor neurons. 

Kleinman D, Karas M, Danilenko M (1996) Stimulation of endometrial cancer cell growth by tamoxifen is associated with increased insulin-like growth factor (IGF)-I induced tyrosine phosphorylation and reduction of IGF binding proteins. Endocrinology 137 1089-1095... 

Guan J, WiUiams CE, Skinner SJ, Mallard EC, Gluckman PD. 1996. The effects of insulin-like growth factor (IGF)-l, IGF-2, and des-IGF-1 on neuronal loss after hypoxic-ischemic brain injury in adult rats evidence for a role for IGE binding proteins. Endocrinology 137 893-898. 

Insulin, growth factors Monomeric Tyrosine kinase activity of receptor Insulin Insulin-like growth factor (IGF) Platelet-derived growth factor (PDGF) Epidermal growth ftictor (EGF)... 

GH primarily displays an anabolic activity. It partially stimulates the growth of bone, muscle and cartilage cells directly. Binding of GH to its hepatic receptor results in the synthesis and release of insulin-like growth factor (IGF-1), which mediates most of GH s growth-promoting activity on, for example, bone and skeletal muscle (Chapter 7). The major effeets mediated by hGH are summarized in Table 8.6. 

An example of how ES-MS can be used to determine minor impurities in a recombinant protein is shown in Figure 9.33, where some small additional ions in the mass spectrum of recombinant insulin-like growth factor (IGF) can be seen. The major ions in the spectrum are due to IGF itself bearing varying charge but the minor impurities also give rise to peaks and these can be interpreted as shown in Table 9.4. 

Insulin aspart is absorbed nearly twice as fast as regular insulin. In addition to binding to the insulin receptor, insulin aspart also binds to the insuUnlike growth factor (IGF-1) receptor, which shares structural homology with the insulin receptor. However, at physiological and pharmacological levels, the metabolic effects of insulin aspart predominate. Both lispro insulin and insulin aspart have relatively fast onsets and short... 

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