Summary: Insulin-like polypeptides made by the liver and some fibroblasts and released into the blood when stimulated by SOMATOTROPIN. They cause sulfate incorporation into collagen, RNA, and DNA synthesis, which are prerequisites to cell division and growth of the organism.

Top Publications

  1. Zimmermann K, Wittman M, Saulnier M, Velaparthi U, Langley D, Sang X, et al. Balancing oral exposure with Cyp3A4 inhibition in benzimidazole-based IGF-IR inhibitors. Bioorg Med Chem Lett. 2008;18:4075-80 pubmed publisher
    ..The use of malonate as methyl anion synthon via S(N)Ar reaction and double decarboxylation under mild conditions is demonstrated. ..
  2. Chell J, Brand A. Nutrition-responsive glia control exit of neural stem cells from quiescence. Cell. 2010;143:1161-73 pubmed publisher
  3. Wheatcroft S, Kearney M. IGF-dependent and IGF-independent actions of IGF-binding protein-1 and -2: implications for metabolic homeostasis. Trends Endocrinol Metab. 2009;20:153-62 pubmed publisher
    ..Here, we review the evolving roles of IGFBP-1 and IGFBP-2 in metabolic homeostasis, summarize their effects on IGF bioactivity and explore putative mechanisms by which they might exert IGF-independent cellular actions. ..
  4. Okamoto N, Yamanaka N, Yagi Y, Nishida Y, Kataoka H, O Connor M, et al. A fat body-derived IGF-like peptide regulates postfeeding growth in Drosophila. Dev Cell. 2009;17:885-91 pubmed publisher
    ..These data indicate that DILP6 is a functional, as well as a structural, counterpart of vertebrate IGFs. Our data provide in vivo evidence for a role of ILPs in determining adult body size through the regulation of postfeeding growth...
  5. Ikeya T, Broughton S, Alic N, Grandison R, Partridge L. The endosymbiont Wolbachia increases insulin/IGF-like signalling in Drosophila. Proc Biol Sci. 2009;276:3799-807 pubmed publisher
    ..This effect of Wolbachia infection on IIS could have an evolutionary explanation, and has some implications for studies of IIS in Drosophila and other organisms that harbour endosymbionts. ..
  6. Tripathi G, Salih D, Drozd A, Cosgrove R, Cobb L, Pell J. IGF-independent effects of insulin-like growth factor binding protein-5 (Igfbp5) in vivo. FASEB J. 2009;23:2616-26 pubmed publisher
    ..This study is also the first to suggest significant IGF-independent actions for IGFBP-5 during development. ..
  7. Maki R. Small is beautiful: insulin-like growth factors and their role in growth, development, and cancer. J Clin Oncol. 2010;28:4985-95 pubmed publisher
    ..Greater success with these agents clinically is expected when combining the agents with inhibitors of other cell signaling pathways in which cross-resistance has been observed. ..
  8. Clayton P, Banerjee I, Murray P, Renehan A. Growth hormone, the insulin-like growth factor axis, insulin and cancer risk. Nat Rev Endocrinol. 2011;7:11-24 pubmed publisher
    ..Nevertheless, long-term surveillance for cancer incidence in all populations exposed to increased levels of GH is vitally important. ..
  9. Bower N, Johnston I. Transcriptional regulation of the IGF signaling pathway by amino acids and insulin-like growth factors during myogenesis in Atlantic salmon. PLoS ONE. 2010;5:e11100 pubmed publisher
    ..A model depicting the transcriptional regulation of the IGF pathway in Atlantic salmon muscle following feeding is proposed. ..

More Information


  1. Slaidina M, Delanoue R, Gronke S, Partridge L, Leopold P. A Drosophila insulin-like peptide promotes growth during nonfeeding states. Dev Cell. 2009;17:874-84 pubmed publisher
    ..This study reveals a specific class of ILPs induced upon metabolic stress that promotes growth in conditions of nutritional deprivation or following developmentally induced cessation of feeding. ..
  2. Wu J, Zhu A. Targeting insulin-like growth factor axis in hepatocellular carcinoma. J Hematol Oncol. 2011;4:30 pubmed publisher
    ..IGF axis is increasingly recognized as one of the most relevant pathways in HCC and agents targeting this axis can potentially play an important role in the treatment of HCC. ..
  3. Maeda H, Yonou H, Yano K, Ishii G, Saito S, Ochiai A. Prostate-specific antigen enhances bioavailability of insulin-like growth factor by degrading insulin-like growth factor binding protein 5. Biochem Biophys Res Commun. 2009;381:311-6 pubmed publisher
    ..The present study indicates PSA derived from PC cells can enhance IGF bioavailability in the bone microenvironment of PC metastasis, thereby permitting PC survival and malignant progression in the bone microenvironment. ..
  4. García de la serrana D, Vieira V, Andree K, Darias M, Estévez A, Gisbert E, et al. Development temperature has persistent effects on muscle growth responses in gilthead sea bream. PLoS ONE. 2012;7:e51884 pubmed publisher
    ..It was concluded that myogenesis and gene expression patterns during growth are not fixed, but can be modified by temperature during the early stages of the life cycle...
  5. Alic N, Andrews T, Giannakou M, Papatheodorou I, Slack C, Hoddinott M, et al. Genome-wide dFOXO targets and topology of the transcriptomic response to stress and insulin signalling. Mol Syst Biol. 2011;7:502 pubmed publisher
    ..We demonstrate genome-wide evolutionary conservation of dFOXO targets between the fly and the worm Caenorhabditis elegans, enriched for a second tier of regulators including the dHR96/daf-12 nuclear hormone receptor. ..
  6. Annunziata M, Granata R, Ghigo E. The IGF system. Acta Diabetol. 2011;48:1-9 pubmed publisher
    ..The present review summarizes the main aspects of the IGF system biology and the interactions among IGF-I, insulin, insulin analogs and their receptors. ..
  7. Chaves J, Saif M. IGF system in cancer: from bench to clinic. Anticancer Drugs. 2011;22:206-12 pubmed publisher
    ..The researchers review the IGFs pathway and its implications in cancer development and treatment. ..
  8. Slack C, Giannakou M, Foley A, Goss M, Partridge L. dFOXO-independent effects of reduced insulin-like signaling in Drosophila. Aging Cell. 2011;10:735-48 pubmed publisher
  9. Okamoto N, Yamanaka N, Satake H, Saegusa H, Kataoka H, Mizoguchi A. An ecdysteroid-inducible insulin-like growth factor-like peptide regulates adult development of the silkmoth Bombyx mori. FEBS J. 2009;276:1221-32 pubmed publisher
    ..Our results also suggest that the known effects of ecdysteroid on insect adult development may be in part mediated by IGF-like peptides...
  10. Ruan W, Lai M. Insulin-like growth factor binding protein: a possible marker for the metabolic syndrome?. Acta Diabetol. 2010;47:5-14 pubmed publisher
    ..These exciting findings bring us new insight into the elucidation of the metabolic syndrome, which may have important clinical implications. ..
  11. Rosenzweig S, Atreya H. Defining the pathway to insulin-like growth factor system targeting in cancer. Biochem Pharmacol. 2010;80:1115-24 pubmed publisher
    ..In this commentary, we highlight some of the significant aspects of and prospects for targeting the IGF-1R and describe what the future may hold. ..
  12. Doghman M, El Wakil A, Cardinaud B, Thomas E, Wang J, Zhao W, et al. Regulation of insulin-like growth factor-mammalian target of rapamycin signaling by microRNA in childhood adrenocortical tumors. Cancer Res. 2010;70:4666-75 pubmed publisher
    ..Our results reveal a novel mechanism of regulation of mTOR signaling by miRNAs, and they lay the groundwork for clinical evaluation of drugs inhibiting the mTOR pathway for treatment of adrenocortical cancer. ..
  13. Broughton S, Partridge L. Insulin/IGF-like signalling, the central nervous system and aging. Biochem J. 2009;418:1-12 pubmed publisher
    ..Tissue-specific manipulation of IIS and the cellular defence mechanisms that it regulates will better define the ways in which IIS affects neuronal and whole-organism function during aging. ..
  14. Soscia S, Tong M, Xu X, Cohen A, Chu J, Wands J, et al. Chronic gestational exposure to ethanol causes insulin and IGF resistance and impairs acetylcholine homeostasis in the brain. Cell Mol Life Sci. 2006;63:2039-56 pubmed
    ..In conclusion, cerebellar hypoplasia in FAS is mediated by insulin/IGF resistance with attendant impairments in energy production and ACh homeostasis. ..
  15. Kjaergaard M, Gardsvoll H, Hirschberg D, Nielbo S, Mayasundari A, Peterson C, et al. Solution structure of recombinant somatomedin B domain from vitronectin produced in Pichia pastoris. Protein Sci. 2007;16:1934-45 pubmed
    ..The NMR structure was determined for free SMB produced by Pichia and is largely consistent with that solved by X-ray crystallography for SMB in complex with PAI-1. ..
  16. Llewellyn S, Fitzpatrick R, Kenny D, Murphy J, Scaramuzzi R, Wathes D. Effect of negative energy balance on the insulin-like growth factor system in pre-recruitment ovarian follicles of post partum dairy cows. Reproduction. 2007;133:627-39 pubmed
  17. Sferruzzi Perri A, Owens J, Standen P, Taylor R, Heinemann G, Robinson J, et al. Early treatment of the pregnant guinea pig with IGFs promotes placental transport and nutrient partitioning near term. Am J Physiol Endocrinol Metab. 2007;292:E668-76 pubmed
    ..This was consistent with the previously observed increase in fetal growth and survival following IGF treatment...
  18. Arquier N, Geminard C, Bourouis M, Jarretou G, Honegger B, Paix A, et al. Drosophila ALS regulates growth and metabolism through functional interaction with insulin-like peptides. Cell Metab. 2008;7:333-8 pubmed publisher
    ..These results lead us to propose an evolutionary perspective in which ALS function appeared prior to the separation between metabolic and growth effects that are associated with vertebrate insulin and IGFs. ..
  19. Schlueter P, Sang X, Duan C, Wood A. Insulin-like growth factor receptor 1b is required for zebrafish primordial germ cell migration and survival. Dev Biol. 2007;305:377-87 pubmed
    ..Collectively, these data suggest a novel role for IGF signaling in early germline development, potentially via cross-talk with chemokine signaling pathways. ..
  20. Toivonen J, Partridge L. Endocrine regulation of aging and reproduction in Drosophila. Mol Cell Endocrinol. 2009;299:39-50 pubmed publisher
    ..Here we shall review how major hormonal pathways in the fruit fly Drosophila melanogaster interact to influence reproductive capacity and aging. ..
  21. Martin R, Holly J, Davey Smith G, Gunnell D. Associations of adiposity from childhood into adulthood with insulin resistance and the insulin-like growth factor system: 65-year follow-up of the Boyd Orr Cohort. J Clin Endocrinol Metab. 2006;91:3287-95 pubmed
    ..The findings may indicate programming of later insulin sensitivity and consequently IGFBP-2 levels in response to childhood adiposity. The role of IGF-II in obesity-related chronic diseases warrants additional investigation. ..
  22. Gabillard J, Kamangar B, Montserrat N. Coordinated regulation of the GH/IGF system genes during refeeding in rainbow trout (Oncorhynchus mykiss). J Endocrinol. 2006;191:15-24 pubmed
    ..The coordinated regulation of IGF-I, IGFBP-5, and IGFBP-rP1 expression would be a signature for the resumption of myogenic activity. ..
  23. Schar C, Blouse G, Minor K, Peterson C. A deletion mutant of vitronectin lacking the somatomedin B domain exhibits residual plasminogen activator inhibitor-1-binding activity. J Biol Chem. 2008;283:10297-309 pubmed publisher
    ..These results support a model for the assembly of higher order PAI-1-vitronectin complexes via two distinct binding sites in both proteins. ..
  24. Samani A, Yakar S, LeRoith D, Brodt P. The role of the IGF system in cancer growth and metastasis: overview and recent insights. Endocr Rev. 2007;28:20-47 pubmed
  25. de la Monte S, Tong M, Lester Coll N, Plater M, Wands J. Therapeutic rescue of neurodegeneration in experimental type 3 diabetes: relevance to Alzheimer's disease. J Alzheimers Dis. 2006;10:89-109 pubmed
  26. Street M, Seghini P, Ziveri M, Fieni S, Volta C, Neri T, et al. Interleukin-6 and insulin-like growth factor system relationships and differences in the human placenta and fetus from the 35th week of gestation. Growth Horm IGF Res. 2006;16:365-72 pubmed
    ..In conclusion, this study reports new insights into IL-6, IGF-IGFBP relationships within the human placenta and shows the importance of comparing subjects with the same GA. ..
  27. Ronis M, Wands J, Badger T, de la Monte S, Lang C, Calissendorff J. Alcohol-induced disruption of endocrine signaling. Alcohol Clin Exp Res. 2007;31:1269-85 pubmed
    ..Lang; (5) The role of reduced plasma estradiol and impaired estrogen signaling in alcohol-induced bone loss, by Martin J. Ronis; and (6) Short-term influence of alcohol on appetite-regulating hormones in man, by Jan Calissendorff. ..
  28. Pavelic J, Matijevic T, Knezevic J. Biological & physiological aspects of action of insulin-like growth factor peptide family. Indian J Med Res. 2007;125:511-22 pubmed
    ..Consistent with the IGFs autocrine/paracrine regulation of tumour growth, cancer treatment strategies interfering with IGF-R1 signaling have been developed, that may be useful in future diagnostic and therapeutic strategies. ..
  29. Mullis P, Tonella P. Regulation of fetal growth: consequences and impact of being born small. Best Pract Res Clin Endocrinol Metab. 2008;22:173-90 pubmed publisher
    ..In general, growth disorders only become apparent postnatally, but they may well be related to fetal life. Thus, fetal growth always needs to be considered in the overall picture of human growth as well as in its metabolic development. ..
  30. Chesik D, de Keyser J, Wilczak N. Insulin-like growth factor system regulates oligodendroglial cell behavior: therapeutic potential in CNS. J Mol Neurosci. 2008;35:81-90 pubmed publisher
    ..In the present review, we address these issues and consider current therapeutic prospects of oligodendrocyte-targeted IGF-based therapies. ..
  31. Rikhof B, de Jong S, Suurmeijer A, Meijer C, van der Graaf W. The insulin-like growth factor system and sarcomas. J Pathol. 2009;217:469-82 pubmed publisher
    ..Moreover, the occasional occurrence of paraneoplastic hypoglycaemia as a result of the secretion of incompletely processed forms of pro-IGF-II by sarcomas is discussed. ..
  32. de la Monte S, Tong M, Cohen A, Sheedy D, Harper C, Wands J. Insulin and insulin-like growth factor resistance in alcoholic neurodegeneration. Alcohol Clin Exp Res. 2008;32:1630-44 pubmed publisher
    ..The results suggest that alcoholic neurodegeneration in humans is associated with insulin and IGF resistance with attendant impairment of neuronal survival mechanisms and acetylcholine homeostasis. ..
  33. Cohen A, Tong M, Wands J, de la Monte S. Insulin and insulin-like growth factor resistance with neurodegeneration in an adult chronic ethanol exposure model. Alcohol Clin Exp Res. 2007;31:1558-73 pubmed
    ..The reductions in ChAT gene expression most likely contribute to the cognitive and motor deficits that occur with chronic alcohol abuse. ..
  34. Broughton S, Chen H, Riddle A, Kuhn S, Nagalla S, Roberts C, et al. Large-scale generation of highly enriched neural stem-cell-derived oligodendroglial cultures: maturation-dependent differences in insulin-like growth factor-mediated signal transduction. J Neurochem. 2007;100:628-38 pubmed
  35. Frommer K, Reichenmiller K, Schutt B, Hoeflich A, Ranke M, Dodt G, et al. IGF-independent effects of IGFBP-2 on the human breast cancer cell line Hs578T. J Mol Endocrinol. 2006;37:13-23 pubmed
    ..Our results suggest that IGFBP-2-induced gene expressions are of functional significance for proliferation, cell adhesion, cell migration and apoptosis, and showed that IGFBP-2 can promote apoptosis in tumor cells independent of IGF. ..
  36. Belinsky M, Rink L, Cai K, Ochs M, Eisenberg B, Huang M, et al. The insulin-like growth factor system as a potential therapeutic target in gastrointestinal stromal tumors. Cell Cycle. 2008;7:2949-55 pubmed
    ..We also discuss how the IGF pathway may provide additional molecular targets for the treatment of GISTs that respond poorly to IM therapy. ..
  37. Rowlands M, Gunnell D, Harris R, Vatten L, Holly J, Martin R. Circulating insulin-like growth factor peptides and prostate cancer risk: a systematic review and meta-analysis. Int J Cancer. 2009;124:2416-29 pubmed publisher
    ..Associations between IGFBP-3 and prostate cancer were inconsistent, and there was little evidence for a role of IGF-II, IGFBP-1 or IGFBP-2 in prostate cancer risk. ..
  38. Zhou J, Li W, Kamei H, Duan C. Duplication of the IGFBP-2 gene in teleost fish: protein structure and functionality conservation and gene expression divergence. PLoS ONE. 2008;3:e3926 pubmed publisher
    ..The duplicated IGFBP-2 genes may provide additional flexibility in the regulation of IGF activities. ..
  39. Honjoh S, Yamamoto T, Uno M, Nishida E. Signalling through RHEB-1 mediates intermittent fasting-induced longevity in C. elegans. Nature. 2009;457:726-30 pubmed publisher
    ..These findings identify the essential role of signalling by RHEB-1 in IF-induced longevity and gene expression changes, and suggest a molecular link between the IF-induced longevity and the insulin/IGF-like signalling pathway. ..
  40. Bower N, Li X, Taylor R, Johnston I. Switching to fast growth: the insulin-like growth factor (IGF) system in skeletal muscle of Atlantic salmon. J Exp Biol. 2008;211:3859-70 pubmed publisher
    ..Together, these data show that switching to fast growth in Atlantic salmon skeletal muscle involves the local upregulation of IGF-I, IGFBP-5.2 and IGFBP-4, with downregulation of IGFBP-2.1. ..
  41. Schar C, Jensen J, Christensen A, Blouse G, Andreasen P, Peterson C. Characterization of a site on PAI-1 that binds to vitronectin outside of the somatomedin B domain. J Biol Chem. 2008;283:28487-96 pubmed publisher
    ..We hypothesize that, together, the two sites form an extended binding area that may promote assembly of higher order vitronectin-PAI-1 complexes. ..
  42. Buch S, Melcher C, Bauer M, Katzenberger J, Pankratz M. Opposing effects of dietary protein and sugar regulate a transcriptional target of Drosophila insulin-like peptide signaling. Cell Metab. 2008;7:321-32 pubmed publisher
    ..tobi is thus a target of the insulin- and glucagon-like signaling system that responds oppositely to dietary protein and sugar. ..
  43. Forbes K, Westwood M. The IGF axis and placental function. a mini review. Horm Res. 2008;69:129-37 pubmed publisher
  44. Wang D, Jiao B, Hu C, Huang X, Liu Z, Cheng C. Discovery of a gonad-specific IGF subtype in teleost. Biochem Biophys Res Commun. 2008;367:336-41 pubmed publisher
    ..These findings highlight the importance of this novel IGF in teleost gonadal development and reproduction. ..
  45. Zhu W, Shiojima I, Ito Y, Li Z, Ikeda H, Yoshida M, et al. IGFBP-4 is an inhibitor of canonical Wnt signalling required for cardiogenesis. Nature. 2008;454:345-9 pubmed publisher
    ..IGFBP-4 is therefore an inhibitor of the canonical Wnt signalling required for cardiogenesis and provides a molecular link between IGF signalling and Wnt signalling. ..
  46. Street M, Seghini P, Fieni S, Ziveri M, Volta C, Martorana D, et al. Changes in interleukin-6 and IGF system and their relationships in placenta and cord blood in newborns with fetal growth restriction compared with controls. Eur J Endocrinol. 2006;155:567-74 pubmed
    ..As IGFBP-2 has a strong affinity for IGF-II, which is crucial for fetal growth, it could be an important bioregulator of IGF-II in the placenta. ..
  47. Shynlova O, Tsui P, Dorogin A, Langille B, Lye S. Insulin-like growth factors and their binding proteins define specific phases of myometrial differentiation during pregnancy in the rat. Biol Reprod. 2007;76:571-8 pubmed
    ..Igfbp5 gene was induced during postpartum involution. Our results suggest the importance of the IGF system in phenotypic and functional changes of myometrial SMCs throughout gestation in preparation for labor. ..
  48. Weber W, Wallace C, Hansen L, Chester Jones H, Crooker B. Effects of genetic selection for milk yield on somatotropin, insulin-like growth factor-I, and placental lactogen in Holstein cows. J Dairy Sci. 2007;90:3314-25 pubmed
    ..Results also indicate a positive relationship between PL and IGF-I and support the concept that PL plays a role in the regulation of serum IGF-I during gestation. ..
  49. Sang X, Curran M, Wood A. Paracrine insulin-like growth factor signaling influences primordial germ cell migration: in vivo evidence from the zebrafish model. Endocrinology. 2008;149:5035-42 pubmed publisher
    ..Collectively, these studies confirm an in vivo role for IGF signaling in cell migration and identify a candidate ligand gene (igf2b) regulating PGC migration in the zebrafish. ..
  50. Pollak M. Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer. 2008;8:915-28 pubmed publisher
    ..Recent results are encouraging and have justified the expansion of many translational research programmes. ..
  51. Reindl K, Sheridan M. Peripheral regulation of the growth hormone-insulin-like growth factor system in fish and other vertebrates. Comp Biochem Physiol A Mol Integr Physiol. 2012;163:231-45 pubmed publisher
    ..The complex regulation of these system components appears to be both organism- and tissue-specific. ..
  52. Raina K, Agarwal C, Wadhwa R, Serkova N, Agarwal R. Energy deprivation by silibinin in colorectal cancer cells: a double-edged sword targeting both apoptotic and autophagic machineries. Autophagy. 2013;9:697-713 pubmed publisher
  53. Kitamura T, Shimizu T, Ohkawa N, Oda H, Ohtsuki M, Kishiro M. Effects of ghrelin on growth and cardiac function in infants with congenital heart disease. Pediatr Int. 2010;52:358-61 pubmed publisher
    ..Significant correlation between A-Ghr and desacyl-ghrelin in the CHD group was observed. A-Ghr is involved in cardiac function and has little effect on their physique in infants with CHD. ..