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14-September-2008 18:02:46 - factor ILGF ILGF The insulin-like growth factors IGFs are polypeptides with high sequence similarity to insulin. IGFs are part of a complex system that cells use to communicate with their physiologic environment. This complex system often referred to as the IGF axis consists of two cell-surface receptors IGF1R and IGF2R, two ligands IGF-1 and IGF-2, a family of six high-affinity IGF binding proteins IGFBP 1-6, as well as associated IGFBP degrading enzymes, referred to collectively as proteases. Contents 1 IGF1/GH Axis 2 IGF Targets 3 IGF Receptors 4 IGF Binding Proteins 5 Diseases affected by IGF 6 See also 7 References 8 External links IGF1/GH Axis The IGF axis is also commonly referred to as the Growth Hormone/IGF1 Axis. Insulin-like growth factor 1 IGF-1 is mainly secreted by the liver as a result of stimulation by growth hormone GH. IGF-1 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. Insulin-like growth factor 2 IGF-2 is thought to be a primary growth factor required for early development while IGF-I expression is required for achieving maximal growth. 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. Factors that are known to cause variation in the levels of GH and IGF-1 in the circulation include an individuals genetic make-up, the time of day, their age, sex, exercise status, stress levels, genetics, nutrition level and body mass index BMI, disease state, race, estrogen status and xenobiotic intake IGF Targets Almost every cell in the human body is affected by IGF-1, especially cells in muscle, cartilage, bone, liver, kidney, nerves, skin, and lungs.citation needed 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-2 is secreted by the brain, kidney, pancreas and muscle in mammals.citation needed It is more specific in action than IGF-1. In adult humans it is found at 600 times the concentration of insulin.citation needed IGF Receptors Further work is required to determine the main receptors used by these growth factors to elicit their effects. The IGF's are known to bind the IGF-1 receptor, the insulin receptor, the IGF-2 receptor, the insulin-related receptor and possible other receptors. The IGF-1 receptor seems to be the physiologic receptor - IGF-1 binds to it at significantly higher affinity than it binds the insulin receptor. Like the insulin receptor, the IGF-1 receptor is a receptor tyrosine kinase - meaning the receptor signals by causing the addition of a phosphate molecule on particular tyrosines. 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 Binding Proteins IGF-1 and IGF-2 are regulated by a family of proteins 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 addition to their ability to regulate IGFs. Diseases affected by IGF Studies of recent interest show that the Insulin/IGF axis play an important role in aging2. Nematodes, fruit-flies and other organisms have an increased life span when the gene equivalent to the mammalian insulin is knocked out. It is somewhat difficult to relate this finding to the mammal, however, because in the smaller organism there are many genes at least 37 in the nematode 1 that are insulin-like or IGF-1-like, whereas in the mammals insulin-like proteins comprise only 7 members insulin, IGFs, relaxins, EPIL, and relaxin-like factorcitation needed and have apparently distinct roles with some but relatively less crosstalk. On the other hand, simpler organisms typically have fewer receptors only 1 known in the nematode2, and the roles of these other insulins are unknown. Furthermore these animals do not have specialized organs islets of Langerhans which sense insulin in response to glucose homeostasis. Therefore it is an open question as to whether either IGF1 or insulin in the mammal may perturb aging, although there is strong suggestion dietary restriction phenomena are related. 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. Researchers are not in complete agreement about the degree of cancer risk that IGF-1 poses. See also Insulin-like growth factor 1 Insulin-like growth factor 2 Growth hormone treatment HGH controversies References Cohen, Pinchas, et al. Insulin-like growth factors IGFs, IGF receptors, and IGF-binding proteins in primary cultures of prostate epithelial. Journal of Clinical Endocrinology and Metabolism, Vol. 73, No. 2, 1991, pp. 401-07 F. Yaghmaie, O. Saeed, S.A. Garan, M.A. Voelker, A.M. Gouw, W. Freitag, H. Sternberg and P.S. Timiras Age-dependent loss of insulin-like growth factor-1 receptor immunoreactive cells in the supraoptic hypothalamus is reduced in calorically restricted mice. International Journal of Developmental Neuroscience, Vol. 24, Issue 7, 2006, pp. 431-436 Lippman, Marc E. The development of biological therapies for breast cancer. Science, Vol. 259, January 29, 1993, pp. 631-32 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 Scarth, J Modulation of the Growth Hormone-Insulin-Like Growth Factor GH-IGF axis by pharmaceutical, nutraceutical and environmental xenobiotics: an emerging role for xenobiotic metabolizing enzymes and the transcription factors regulating their expression. A review.. Xenobiotica, Vol. 36, 2-3 pp. 119-218 Woods, Alisa G. Deafferentation-induced increases in hippocampal insulin-like growth factor-1 messenger RNA expression are severely attenuated in middle aged and aged rats. Neuroscience, Vol. 83, 3 pp. 663-668 ^ Pierce, et al. Genes and Development 2001 ^ ibid. v d e Endocrine system: hormones/endocrine glands Peptide hormones, Steroid hormones Hypothalamic-pituitary Hypothalamus: TRH, CRH , GnRH, GHRH, somatostatin, dopamine - Posterior pituitary: vasopressin, oxytocin - Anterior pituitary: α FSH, LH, TSH, GH, prolactin, POMC ACTH, MSH, endorphins, lipotropin Adrenal axis Adrenal medulla: epinephrine, norepinephrine - Adrenal cortex: aldosterone, cortisol, DHEA Thyroid axis Thyroid: thyroid hormone T3 and T4 - calcitonin - Parathyroid: PTH Gonadal axis Testis: testosterone, AMH, inhibin - Ovary: estradiol, progesterone, inhibin/activin, relaxin pregnancy Other end. glands Pancreas: glucagon, insulin, somatostatin - Pineal gland: melatonin Non-end. glands Placenta: hCG, HPL, estrogen, progesterone - Kidney: renin, EPO, calcitriol, prostaglandin - Heart atrium: ANP - Stomach: gastrin, ghrelin - Duodenum: CCK, GIP, secretin, motilin, VIP - Ileum: enteroglucagon - Adipose tissue: leptin, adiponectin, resistin - Thymus: Thymosin - Thymopoietin - Thymulin - Skeleton: Osteocalcin - Liver/other: Insulin-like growth factor IGF-1, IGF-2 Target-derived NGF, BDNF, NT-3 v d e Growth factors Fibroblast FGF receptor ligands: 1 acidic/2 basic/5 · 3/4/6 · 7/10/22 · 8/17/18 · 9/16/20 FGF homologous factors: 11 · 12 · 13 · 14 hormone-like: 19 · 21 · 23 EGF-like domain TGFα · Epidermal · Heparin-binding EGF-like TGFβ pathway TGFβ 1, 2, 3 Insulin-like 1 · 2 Platelet-derived A · B · C · D Vascular endothelial A · B · C · D · PGF Other Nerve · Hepatocyte see also growth factor receptors External links Retrieved from http://en..org/wiki/Insulin-like_growth_factor Categories: Cell signaling | Signal transduction | Peptide hormones | Growth factors | EndocrinologyHidden categories: All articles with statements | Articles with statements since November 2007 | Articles with statements since December 2007 Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Deutsch Esperanto Italiano עברית 日本語 Polski Suomi This page was last modified on 23 August 2008, at 08:07
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