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Gene Review

IGF2  -  insulin-like growth factor 2

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Disease relevance of IGF2

  • There was a significant (P<0.01) effect of protein supplementation in second trimester upon IGF II levels and a significant (P<0.05) negative correlation between calf birth weight and IGF II levels [1].
  • Fetal weight and instantaneous growth rate (IGR) were positively correlated to maternal NEFA and PL and negatively correlated to maternal IGF-I and IGF-II [2].
  • To characterize the effect of GH on the levels of IGF I and IGF II mRNA in a teleost, 10 micrograms of bovine GH (bGH) per g of body weight was administered to juvenile rainbow trout (Oncorhynchus mykiss) through i.p. injection [3].
  • Since we previously demonstrated that insulin-like growth factor II (IGF-II) is an autocrine growth factor in human rhabdomyosarcoma (RMS), we studied the effect of suramin on the growth of human RMS cells [4].
  • A synthetic gene encoding the signal peptide and the N-terminal sequence of bombyxin, an insect insulin-like peptide, and the 58 amino acids of the C-terminal sequence of human insulin-like growth factor II (IGF II) has been expressed using the baculovirus system [5].

Psychiatry related information on IGF2


High impact information on IGF2

  • In the present study, we have characterized the receptors and the growth-promoting effect of insulinlike growth factor I (IGF-I) and multiplication-stimulating activity (MSA, an IGF-II) on endothelial cells and pericytes from calf retinal capillaries and on endothelial and smooth muscle cells from calf aorta [7].
  • The GH-dependent appearance of IGF II mRNA in the liver and pyloric ceca suggests important roles for this peptide hormone exclusive of IGF I [3].
  • The levels of IGF I and IGF II mRNA were determined simultaneously, by using RNase protection assays, in the liver, pyloric ceca, kidney, and gill at 0, 1, 3, 6, 12, 24, 48, and 72 hr after injection [3].
  • In primary hepatocyte culture, IGF I and IGF II mRNA levels increased in a bGH dose-dependent fashion, with ED50 values of approximately 45 and approximately 6 ng of bGH per ml, respectively [3].
  • Our data indicate that suramin exerts its effect on RMS cell growth by interfering with the binding of IGF-II to the type I IGF receptor, thereby interrupting the IGF-II autocrine growth in these cells [4].

Chemical compound and disease context of IGF2

  • This study confirms the close inter-relationship between the thyroid hormone and IGF axes in cattle and indicates possible effects of Gram-negative mastitis infection on IGF-II metabolism [8].

Biological context of IGF2


Anatomical context of IGF2

  • Only relative abundance (RA) of IGF2 gene was higher in oocytes matured with fafBSA [13].
  • IGF-I and IGF-II, but not insulin, were found to increase the proportion of embryos which formed blastocysts [10].
  • It was found that IGF-1 concentrations increased during growth from 280 ng/ml in small follicles to 489 ng/ml in preovulatory follicles; IGF-2 appeared to remain constant in follicular fluid and in cysts (275 ng/ml) [14].
  • The IGF-II mRNA was increased in the endometrium of pregnant and bST-treated cows fed the control diet [15].
  • Ligand blot analysis with 125I-labeled IGF-II revealed the presence of four prominent polypeptide bands of approximate molecular masses 24, 31, and 36 kDa, and a broad band extending from 46 to 53 kDa, in conditioned media samples prepared from oviduct primary cultures [16].

Associations of IGF2 with chemical compounds

  • Cells were treated with various concentrations (3-500ng/ml) and combinations of IGF-I, IGF-II, FSH, LH, E2, INS, leptin and (or) cortisol for 24h (Experiments 1-10) [17].
  • The presence of bound IGF-II resulted in protection of tyrosine at position 60 from iodination measured by the relative loss of tyrosine specific fluorescence and the incorporation of the radioisotope 125I [18].
  • The relationship between plasma and lymph concentrations for IGF-II, bST, insulin, glucose, urea nitrogen, and nonesterified fatty acids were similar during bST treatment [19].
  • In contrast, changes in IGF-II, bST, insulin, glucose, urea nitrogen, and nonesterified fatty acids that were caused by feed deprivation followed similar patterns in plasma and lymph [19].
  • Since IGF-II exerts its mitogenic effects on RMS cells by binding to the type I receptor, we performed radioreceptor assays using 125I-IGF-I and found that suramin displaced 125I-IGF-I from the type I IGF receptor [4].

Physical interactions of IGF2

  • IGFII-specific binding is consistently five times greater than that of IGFI [20].
  • The ovary bearing the DF was surgically removed by colpotomy, and individual follicles were utilized to study changes in concentrations of insulin like growth factor-I (IGF-I) and -II (IGF-II) and changes in amounts and proportions of the different IGF-binding proteins (IGFBP) present in follicular fluid (FF) [21].
  • IGF-II ligand blots confirm these tissue-specific differences in binding and show that each ocular tissue contains IGFBP-2 [22].
  • They are secreted by seminal vesicles and they bind to the choline phospholipids composing the sperm plasma membrane upon ejaculation. these proteins contain two homologous domains that are similar to the type II structure present in the putative insulin-like growth factor II (IGF-II) binding domain of the IGF-II receptor [23].

Regulatory relationships of IGF2

  • Plasma IGF-II levels were decreased by rbGH treatment during the well fed phase, but the responses to treatment during the fasted phase were variable, suggesting that plasma IGF-II is regulated in a different manner than plasma IGF-I [24].
  • IGF-I and IGF-II stimulated tyrosine kinase activity and autophosphorylation of the IGF-I receptor beta-subunit (Mr approximately 94,000) with equal potency (ED50 approximately 1 nM), whereas insulin was approximately 5 times less potent [25].
  • Erythrotropin II stimulated thymidine incorporation and potentiated the action of erythropoietin in cultures of erythroid cells from fetal rat liver [26].

Other interactions of IGF2

  • The expression of three genes (IGF2R, IGFBP-4, and IGF2) in some tissues showed significant differences between AF cell-derived and FF cell-derived clones [27].
  • The presence of IGF II, IGF-IR, GHR, IR and IGFBP-1, -2 and -3 mRNA was confirmed in the liver of 8-d old calves and older cattle as well, and among newborn calves their presence was independent of differences in nutrition [28].
  • Furthermore, it has been proposed that loss of imprinting of the insulin-like growth factor II receptor gene and the consequent over-production of IGF-II may be involved in the aetiology of the Enlarged Offspring Syndrome, which occurs as an artefact of in vitro embryo production [10].
  • Expression of IGF-I, IGF-II, and IGF binding protein-5 mRNA was assessed by real time reverse transcription-polymerase chain reaction [29].
  • The amounts of IGFBP-3 in conditioned media were relatively low under basal conditions when analyzed by ligand blotting with 125I-IGF-II, but were increased dramatically relative to serum-free controls by exposure to IGF-I (100 ng/ml) or IGF-II (100 ng/ml) for 24 h [30].

Analytical, diagnostic and therapeutic context of IGF2

  • Relative expression of IGF-I and IGF-II mRNA was determined by real-time PCR and plasma concentrations of IGF-I were measured using a validated fluoroimmunoassay [31].
  • In vivo studies and results based on cell lines or primary cell cultures show that IGF-I and IGF-II stimulate both proliferation and differentiation of myoblasts and satellite cells in a time and concentration-dependent way, via interaction with type I IGF receptors [32].
  • 3. Northern blot analysis of intestine, liver, kidney and spleen from bovine fetuses showed multiple IGF II RNA species which are more similar to the human than to the rodent mRNAs [33].
  • Here we describe the sequence analysis of a CpG-rich DNA fragment from the 5' untranslated region spanning exons and introns 4 and 5 and the identification of a previously unknown DMR in exon 10 of the bovine IGF2 gene [34].
  • At 37 degrees C, internalization determined by both resistance to an acid wash and electron microscopy was rapid with 50-70% of bound IGF II and insulin internalized at 60 min [35].


  1. Insulin-like growth factor levels during pregnancy in the cow are affected by protein supplementation in the maternal diet. Perry, V.E., Norman, S.T., Daniel, R.C., Owens, P.C., Grant, P., Doogan, V.J. Anim. Reprod. Sci. (2002) [Pubmed]
  2. Serum concentrations of insulin-like growth factors and placental lactogen during gestation in cattle. II. Maternal profiles. Hossner, K.L., Holland, M.D., Williams, S.E., Wallace, C.R., Niswender, G.D., Odde, K.G. Domest. Anim. Endocrinol. (1997) [Pubmed]
  3. Appearance of insulin-like growth factor mRNA in the liver and pyloric ceca of a teleost in response to exogenous growth hormone. Shamblott, M.J., Cheng, C.M., Bolt, D., Chen, T.T. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  4. Suramin inhibits the growth of human rhabdomyosarcoma by interrupting the insulin-like growth factor II autocrine growth loop. Minniti, C.P., Maggi, M., Helman, L.J. Cancer Res. (1992) [Pubmed]
  5. Accurate processing and secretion in the baculovirus expression system of an erythroid-cell-stimulating factor consisting of a chimaera of insulin-like growth factor II and an insect insulin-like peptide. Congote, L.F., Li, Q. Biochem. J. (1994) [Pubmed]
  6. Radioimmunoassay for insulin-like growth factor II (IGF-II). Asakawa, K., Hizuka, N., Takano, K., Fukuda, I., Sukegawa, I., Demura, H., Shizume, K. Endocrinol. Jpn. (1990) [Pubmed]
  7. Receptors and growth-promoting effects of insulin and insulinlike growth factors on cells from bovine retinal capillaries and aorta. King, G.L., Goodman, A.D., Buzney, S., Moses, A., Kahn, C.R. J. Clin. Invest. (1985) [Pubmed]
  8. Periparturient endocrine and metabolic changes in healthy cows and in cows affected by mastitis. Nikolić, J.A., Kulcsár, M., Kátai, L., Nedić, O., Jánosi, S., Huszenicza, G. Journal of veterinary medicine. A, Physiology, pathology, clinical medicine. (2003) [Pubmed]
  9. Linkage mapping of IGF2 on cattle chromosome 29. Goodall, J.J., Schmutz, S.M. Anim. Genet. (2003) [Pubmed]
  10. Regulation of apoptosis in the bovine blastocyst by insulin and the insulin-like growth factor (IGF) superfamily. Byrne, A.T., Southgate, J., Brison, D.R., Leese, H.J. Mol. Reprod. Dev. (2002) [Pubmed]
  11. A role for LH in the regulation of expression of mRNAs encoding components of the insulin-like growth factor (IGF) system in the ovine corpus luteum. Hastie, P.M., Haresign, W. Anim. Reprod. Sci. (2006) [Pubmed]
  12. Effect of negative energy balance on the insulin-like growth factor system in pre-recruitment ovarian follicles of post partum dairy cows. Llewellyn, S., Fitzpatrick, R., Kenny, D.A., Murphy, J.J., Scaramuzzi, R.J., Wathes, D.C. Reproduction (2007) [Pubmed]
  13. Maturation medium supplements affect transcript level of apoptosis and cell survival related genes in bovine blastocysts produced in vitro. Warzych, E., Wrenzycki, C., Peippo, J., Lechniak, D. Mol. Reprod. Dev. (2007) [Pubmed]
  14. A comparison of hormone levels in follicle-lutein-cysts and in normal bovine ovarian follicles. Einspanier, R., Schuster, H., Schams, D. Theriogenology (1993) [Pubmed]
  15. Pregnancy, bovine somatotropin, and dietary n-3 fatty acids in lactating dairy cows: I. Ovarian, conceptus, and growth hormone-insulin-like growth factor system responses. Bilby, T.R., Sozzi, A., Lopez, M.M., Silvestre, F.T., Ealy, A.D., Staples, C.R., Thatcher, W.W. J. Dairy Sci. (2006) [Pubmed]
  16. Bovine oviductal and embryonic insulin-like growth factor binding proteins: possible regulators of "embryotrophic" insulin-like growth factor circuits. Winger, Q.A., de los Rios, P., Han, V.K., Armstrong, D.T., Hill, D.J., Watson, A.J. Biol. Reprod. (1997) [Pubmed]
  17. Real-time RT-PCR quantification of pregnancy-associated plasma protein-A mRNA abundance in bovine granulosa and theca cells: Effects of hormones in vitro. Aad, P.Y., Voge, J.L., Santiago, C.A., Malayer, J.R., Spicer, L.J. Domest. Anim. Endocrinol. (2006) [Pubmed]
  18. The insulin-like growth factor (IGF) binding site of bovine insulin-like growth factor binding protein-2 (bIGFBP-2) probed by iodination. Hobba, G.D., Forbes, B.E., Parkinson, E.J., Francis, G.L., Wallace, J.C. J. Biol. Chem. (1996) [Pubmed]
  19. Insulin-like growth factors in plasma and afferent mammary lymph of lactating cows deprived of feed or treated with bovine somatotropin. McGuire, M.A., Dwyer, D.A., Bauman, D.E., Smith, D.F. J. Dairy Sci. (1998) [Pubmed]
  20. Characterisation and location of insulin-like-growth factor (IGF) receptors in the foetal bovine Semitendinosus muscle. Listrat, A., Jammes, H., Djianne, J., Geay, Y., Robelin, J. Reprod. Nutr. Dev. (1999) [Pubmed]
  21. Insulin-like growth factor system in bovine first-wave dominant and subordinate follicles. de la Sota, R.L., Simmen, F.A., Diaz, T., Thatcher, W.W. Biol. Reprod. (1996) [Pubmed]
  22. Distribution of IGF-I and -II, IGF binding proteins (IGFBPs) and IGFBP mRNA in ocular fluids and tissues: potential sites of synthesis of IGFBPs in aqueous and vitreous. Arnold, D.R., Moshayedi, P., Schoen, T.J., Jones, B.E., Chader, G.J., Waldbillig, R.J. Exp. Eye Res. (1993) [Pubmed]
  23. Major proteins of bovine seminal fluid bind to insulin-like growth factor-II. Desnoyers, L., Manjunath, P. J. Biol. Chem. (1994) [Pubmed]
  24. Pretreatment with bovine growth hormone is as effective as treatment during metabolic stress to reduce catabolism in fasted lambs. Ogawa, E., Breier, B.H., Bauer, M.K., Gallaher, B.W., Grant, P.A., Walton, P.E., Owens, J.A., Gluckman, P.D. Endocrinology (1996) [Pubmed]
  25. Chromaffin cells express two types of insulin-like growth factor receptors. Danielsen, A., Larsen, E., Gammeltoft, S. Brain Res. (1990) [Pubmed]
  26. Isolation of two biologically active peptides, erythrotropin I and erythrotropin II from fetal calf intestine. Congote, L.F. Biochem. Biophys. Res. Commun. (1983) [Pubmed]
  27. Expression of insulin-like growth factors systems in cloned cattle dead within hours after birth. Li, S., Li, Y., Yu, S., Du, W., Zhang, L., Dai, Y., Liu, Y., Li, N. Mol. Reprod. Dev. (2007) [Pubmed]
  28. mRNA of insulin-like growth factor (IGF) quantification and presence of IGF binding proteins, and receptors for growth hormone, IGF-I and insulin, determined by reverse transcribed polymerase chain reaction, in the liver of growing and mature male cattle. Cordano, P., Hammon, H.M., Morel, C., Zurbriggen, A., Blum, J.W. Domest. Anim. Endocrinol. (2000) [Pubmed]
  29. Exposure to short day photoperiod during the dry period enhances mammary growth in dairy cows. Wall, E.H., Auchtung, T.L., Dahl, G.E., Ellis, S.E., McFadden, T.B. J. Dairy Sci. (2005) [Pubmed]
  30. Regulation of IGF binding protein synthesis by a bovine mammary epithelial cell line. Cohick, W.S., Turner, J.D. J. Endocrinol. (1998) [Pubmed]
  31. Effects of recombinant bovine somatotropin on growth and abundance of mRNA for IGF-I and IGF-II in channel catfish (Ictalurus punctatus). Peterson, B.C., Waldbieser, G.C., Bilodeau, L. J. Anim. Sci. (2005) [Pubmed]
  32. Basic principles of muscle development and growth in meat-producing mammals as affected by the insulin-like growth factor (IGF) system. Oksbjerg, N., Gondret, F., Vestergaard, M. Domest. Anim. Endocrinol. (2004) [Pubmed]
  33. Nucleotide sequence of the central coding region of bovine erythrotropin/insulin-like growth factor II cDNA from fetal intestine and northern analysis of the major IGF II transcripts at the time of hepatic erythropoiesis. Congote, L.F., Mazza, L., Palfree, R.G. Comp. Biochem. Physiol., B (1992) [Pubmed]
  34. The bovine IGF2 gene is differentially methylated in oocyte and sperm DNA. Gebert, C., Wrenzycki, C., Herrmann, D., Gröger, D., Reinhardt, R., Hajkova, P., Lucas-Hahn, A., Carnwath, J., Lehrach, H., Niemann, H. Genomics (2006) [Pubmed]
  35. Comparative studies on insulin-like growth factor II and insulin processing by vascular endothelial cells. Hachiya, H.L., Carpentier, J.L., King, G.L. Diabetes (1986) [Pubmed]
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