3963Accesses
166Citations
8 Altmetric
1Mention
Abstract
The insulin-like growth factor (IGF) system plays essential role in the regulation of cell growth, proliferation and survival and affects nearly every organ system in the body. IGF-I, which has a high structural similarity to insulin, exerts growth-promoting effects, influences glucose metabolism and has neuroprotective and cardioprotective effects, partly because of its cell-proliferative and antiapoptotic properties. Aberrations in the IGF system may associate with various pathological conditions, including cancer. Insulin and its synthetic analogs are known to possess IGF-IR binding affinity, and concern has been raised about their mitogenic potential in humans. The present review summarizes the main aspects of the IGF system biology and the interactions among IGF-I, insulin, insulin analogs and their receptors.
This is a preview of subscription content,log in via an institution to check access.
Access this article
Subscribe and save
- Starting from 10 chapters or articles per month
- Access and download chapters and articles from more than 300k books and 2,500 journals
- Cancel anytime
Buy Now
Price includes VAT (Japan)
Instant access to the full article PDF.

Similar content being viewed by others
Explore related subjects
Discover the latest articles, books and news in related subjects, suggested using machine learning.References
Le Roith D (2003) The insulin-like growth factor system. Exp Diabesity Res 4(4):205–212. doi:9DM2KUX7VXW0N7H6[pii]10.1155/EDR.2003.205
Federici M, Porzio O, Zucaro L, Fusco A, Borboni P, Lauro D, Sesti G (1997) Distribution of insulin/insulin-like growth factor-i hybrid receptors in human tissues. Mol Cell Endocrinol 129(2):121–126. doi:S0303-7207(97)04050-1[pii]
Salmon WD Jr, Daughaday WH (1957) A hormonally controlled serum factor which stimulates sulfate incorporation by cartilage in vitro. J Lab Clin Med 49(6):825–836
Daughaday WH, Hall K, Raben MS, Salmon WD Jr, van den Brande JL, van Wyk JJ (1972) Somatomedin: proposed designation for sulphation factor. Nature 235(5333):107
Froesch ER, Buergi H, Ramseier EB, Bally P, Labhart A (1963) Antibody-suppressible and nonsuppressible insulin-like activities in human serum and their physiologic significance. An insulin assay with adipose tissue of increased precision and specificity. J Clin Invest 42:1816–1834. doi:10.1172/JCI104866
Blundell TL, Bedarkar S, Rinderknecht E, Humbel RE (1978) Insulin-like growth factor: a model for tertiary structure accounting for immunoreactivity and receptor binding. Proc Natl Acad Sci USA 75(1):180–184
Rinderknecht E, Humbel RE (1978) The amino acid sequence of human insulin-like growth factor i and its structural homology with proinsulin. J Biol Chem 253(8):2769–2776
Klapper DG, Svoboda ME, Van Wyk JJ (1983) Sequence analysis of somatomedin-c: confirmation of identity with insulin-like growth factor i. Endocrinology 112(6):2215–2217
Daughaday WH, Hall K, Salmon WD Jr, Van den Brande JL, Van Wyk JJ (1987) On the nomenclature of the somatomedins and insulin-like growth factors. J Clin Endocrinol Metab 65(5):1075–1076
Clemmons DR (2006) Involvement of insulin-like growth factor-i in the control of glucose homeostasis. Curr Opin Pharmacol 6(6):620–625. doi:S1471-4892(06)00167-6[pii]10.1016/j.coph.2006.08.006
Kaplan SA, Cohen P (2007) The somatomedin hypothesis 2007: 50 years later. J Clin Endocrinol Metab 92(12):4529–4535. doi:jc.2007-0526[pii]10.1210/jc.2007-0526
Brissenden JE, Ullrich A, Francke U (1984) Human chromosomal mapping of genes for insulin-like growth factors i and ii and epidermal growth factor. Nature 310(5980):781–784
Tricoli JV, Rall LB, Scott J, Bell GI, Shows TB (1984) Localization of insulin-like growth factor genes to human chromosomes 11 and 12. Nature 310(5980):784–786
Rotwein P, Pollock KM, Didier DK, Krivi GG (1986) Organization and sequence of the human insulin-like growth factor i gene. Alternative RNA processing produces two insulin-like growth factor i precursor peptides. J Biol Chem 261(11):4828–4832
Smith PJ, Spurrell EL, Coakley J, Hinds CJ, Ross RJ, Krainer AR, Chew SL (2002) An exonic splicing enhancer in human igf-i pre-mrna mediates recognition of alternative exon 5 by the serine-arginine protein splicing factor-2/alternative splicing factor. Endocrinology 143(1):146–154
Sussenbach JS, Steenbergh PH, Holthuizen P (1992) Structure and expression of the human insulin-like growth factor genes. Growth Regul 2(1):1–9
Li CH, Yamashiro D, Gospodarowicz D, Kaplan SL, Van Vliet G (1983) Total synthesis of insulin-like growth factor i (somatomedin c). Proc Natl Acad Sci USA 80(8):2216–2220
Blundell TL, Bedarkar S, Humbel RE (1983) Tertiary structures, receptor binding, and antigenicity of insulin like growth factors. Fed Proc 42(9):2592–2597
Clemmons DR (1997) Insulin-like growth factor binding proteins and their role in controlling igf actions. Cytokine Growth Factor Rev 8(1):45–62. doi:S1359610196000536[pii]
Baxter RC, Martin JL (1989) Binding proteins for the insulin-like growth factors: structure, regulation and function. Prog Growth Factor Res 1(1):49–68
Firth SM, Baxter RC (2002) Cellular actions of the insulin-like growth factor binding proteins. Endocr Rev 23(6):824–854
Rapp R, Deger A, Blum W, Koch R, Weber U (1988) Characterization of the protein which binds insulin-like growth factor in human serum. Eur J Biochem 172(2):421–425
Le Roith D, Bondy C, Yakar S, Liu JL, Butler A (2001) The somatomedin hypothesis: 2001. Endocr Rev 22(1):53–74
Kim HS, Ingermann AR, Tsubaki J, Twigg SM, Walker GE, Oh Y (2004) Insulin-like growth factor-binding protein 3 induces caspase-dependent apoptosis through a death receptor-mediated pathway in mcf-7 human breast cancer cells. Cancer Res 64(6):2229–2237
Perks CM, Newcomb PV, Norman MR, Holly JM (1999) Effect of insulin-like growth factor binding protein-1 on integrin signalling and the induction of apoptosis in human breast cancer cells. J Mol Endocrinol 22(2):141–150
Granata R, Trovato L, Garbarino G, Taliano M, Ponti R, Sala G, Ghidoni R, Ghigo E (2004) Dual effects of igfbp-3 on endothelial cell apoptosis and survival: involvement of the sphingolipid signaling pathways. FASEB J 18(12):1456–1458. doi:10.1096/fj.04-1618fje04-1618fje[pii]
Yamada PM, Lee KW (2009) Perspectives in mammalian igfbp-3 biology: local vs. systemic action. Am J Physiol Cell Physiol 296(5):C954–C976. doi:00598.2008[pii]10.1152/ajpcell.00598.2008
Clemmons DR (2009) Role of igf-i in skeletal muscle mass maintenance. Trends Endocrinol Metab 20(7):349–356. doi:S1043-2760(09)00090-3[pii]10.1016/j.tem.2009.04.002
Heldin CH, Ostman A (1996) Ligand-induced dimerization of growth factor receptors: variations on the theme. Cytokine Growth Factor Rev 7(1):3–10. doi:1359610196000020[pii]
House PD, Weidemann MJ (1970) Characterization of an [125 i]-insulin binding plasma membrane fraction from rat liver. Biochem Biophys Res Commun 41(3):541–548. doi:0006-291X(70)90046-X[pii]
Freychet P, Roth J, Neville DM Jr (1971) Insulin receptors in the liver: specific binding of (125 i)insulin to the plasma membrane and its relation to insulin bioactivity. Proc Natl Acad Sci USA 68(8):1833–1837
Cuatrecasas P (1971) Insulin–receptor interactions in adipose tissue cells: direct measurement and properties. Proc Natl Acad Sci USA 68(6):1264–1268
Gammeltoft S, Gliemann J (1973) Binding and degradation of 125i-labelled insulin by isolated rat fat cells. Biochim Biophys Acta 320(1):16–32. doi:0304-4165(73)90161-X[pii]
Yip CC, Yeung CW, Moule ML (1980) Photoaffinity labeling of insulin receptor proteins of liver plasma membrane preparations. Biochemistry 19(1):70–76
Massague J, Czech MP (1982) The subunit structures of two distinct receptors for insulin-like growth factors i and ii and their relationship to the insulin receptor. J Biol Chem 257(9):5038–5045
Shia MA, Pilch PF (1983) The beta subunit of the insulin receptor is an insulin-activated protein kinase. Biochemistry 22(4):717–721
Roth RA, Cassell DJ (1983) Insulin receptor: evidence that it is a protein kinase. Science 219(4582):299–301
Kasuga M, Fujita-Yamaguchi Y, Blithe DL, Kahn CR (1983) Tyrosine-specific protein kinase activity is associated with the purified insulin receptor. Proc Natl Acad Sci USA 80(8):2137–2141
Kasuga M, Fujita-Yamaguchi Y, Blithe DL, White MF, Kahn CR (1983) Characterization of the insulin receptor kinase purified from human placental membranes. J Biol Chem 258(18):10973–10980
Pashmforoush M, Chan SJ, Steiner DF (1996) Structure and expression of the insulin-like peptide receptor from amphioxus. Mol Endocrinol 10(7):857–866
Megyesi K, Kahn CR, Roth J, Neville DM Jr, Nissley SP, Humbel RE, Froesch ER (1975) The nsila-s receptor in liver plasma membranes. Characterization and comparison with the insulin receptor. J Biol Chem 250(23):8990–8996
Marshall RN, Underwood LE, Voina SJ, Foushee DB, Van Wyk JJ (1974) Characterization of the insulin and somatomedin-c receptors in human placental cell membranes. J Clin Endocrinol Metab 39(2):283–292
Bhaumick B, Bala RM, Hollenberg MD (1981) Somatomedin receptor of human placenta: solubilization, photolabeling, partial purification, and comparison with insulin receptor. Proc Natl Acad Sci USA 78(7):4279–4283
Chernausek SD, Jacobs S, Van Wyk JJ (1981) Structural similarities between human receptors for somatomedin c and insulin: analysis by affinity labeling. Biochemistry 20(26):7345–7350
Jacobs S, Kull FC Jr, Earp HS, Svoboda ME, Van Wyk JJ, Cuatrecasas P (1983) Somatomedin-c stimulates the phosphorylation of the beta-subunit of its own receptor. J Biol Chem 258(16):9581–9584
Rubin JB, Shia MA, Pilch PF (1983) Stimulation of tyrosine-specific phosphorylation in vitro by insulin-like growth factor i. Nature 305(5933):438–440
Ullrich A, Gray A, Tam AW, Yang-Feng T, Tsubokawa M, Collins C, Henzel W, Le Bon T, Kathuria S, Chen E et al (1986) Insulin-like growth factor i receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity. EMBO J 5(10):2503–2512
Jacobs S, Kull FC Jr, Cuatrecasas P (1983) Monensin blocks the maturation of receptors for insulin and somatomedin c: identification of receptor precursors. Proc Natl Acad Sci USA 80(5):1228–1231
Steele-Perkins G, Turner J, Edman JC, Hari J, Pierce SB, Stover C, Rutter WJ, Roth RA (1988) Expression and characterization of a functional human insulin-like growth factor i receptor. J Biol Chem 263(23):11486–11492
Sasaki N, Rees-Jones RW, Zick Y, Nissley SP, Rechler MM (1985) Characterization of insulin-like growth factor i-stimulated tyrosine kinase activity associated with the beta-subunit of type i insulin-like growth factor receptors of rat liver cells. J Biol Chem 260(17):9793–9804
Soos MA, Siddle K (1989) Immunological relationships between receptors for insulin and insulin-like growth factor i. Evidence for structural heterogeneity of insulin-like growth factor i receptors involving hybrids with insulin receptors. Biochem J 263(2):553–563
Soos MA, Field CE, Siddle K (1993) Purified hybrid insulin/insulin-like growth factor-i receptors bind insulin-like growth factor-i, but not insulin, with high affinity. Biochem J 290(Pt 2):419–426
Belfiore A, Frasca F, Pandini G, Sciacca L, Vigneri R (2009) Insulin receptor isoforms and insulin receptor/insulin-like growth factor receptor hybrids in physiology and disease. Endocr Rev 30(6):586–623. doi:er.2008-0047[pii]10.1210/er.2008-0047
Hankins GR, De Souza AT, Bentley RC, Patel MR, Marks JR, Iglehart JD, Jirtle RL (1996) M6p/igf2 receptor: a candidate breast tumor suppressor gene. Oncogene 12(9):2003–2009
O’Gorman DB, Weiss J, Hettiaratchi A, Firth SM, Scott CD (2002) Insulin-like growth factor-ii/mannose 6-phosphate receptor overexpression reduces growth of choriocarcinoma cells in vitro and in vivo. Endocrinology 143(11):4287–4294
Pollak M (2008) Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer 8(12):915–928. doi:nrc2536[pii]10.1038/nrc2536
Shier P, Watt VM (1989) Primary structure of a putative receptor for a ligand of the insulin family. J Biol Chem 264(25):14605–14608
Zhang B, Roth RA (1992) The insulin receptor-related receptor. Tissue expression, ligand binding specificity, and signaling capabilities. J Biol Chem 267(26):18320–18328
Nakae J, Kido Y, Accili D (2001) Distinct and overlapping functions of insulin and IGF-I receptors. Endocr Rev 22(6):818–835
Baker J, Liu JP, Robertson EJ, Efstratiadis A (1993) Role of insulin-like growth factors in embryonic and postnatal growth. Cell 75(1):73–82. doi:0092-8674(93)90680-O[pii]
Hadsell DL (2004) Genetic manipulation of mammary gland development and lactation. Adv Exp Med Biol 554:229–251
Torres-Aleman I (2010) Toward a comprehensive neurobiology of igf-i. Dev Neurobiol 70(5):384–396. doi:10.1002/dneu.20778
Humbert S, Bryson EA, Cordelieres FP, Connors NC, Datta SR, Finkbeiner S, Greenberg ME, Saudou F (2002) The igf-1/akt pathway is neuroprotective in Huntington’s disease and involves Huntingtin phosphorylation by akt. Dev Cell 2(6):831–837. doi:S1534580702001880[pii]
Carro E, Trejo JL, Gomez-Isla T, LeRoith D, Torres-Aleman I (2002) Serum insulin-like growth factor i regulates brain amyloid-beta levels. Nat Med 8(12):1390–1397. doi:10.1038/nm793nm793[pii]
Aleman A, Verhaar HJ, De Haan EH, De Vries WR, Samson MM, Drent ML, Van der Veen EA, Koppeschaar HP (1999) Insulin-like growth factor-i and cognitive function in healthy older men. J Clin Endocrinol Metab 84(2):471–475
Llorens-Martin M, Torres-Aleman I, Trejo JL (2009) Mechanisms mediating brain plasticity: igf1 and adult hippocampal neurogenesis. Neuroscientist 15(2):134–148. doi:15/2/134[pii]10.1177/1073858408331371
Li B, Setoguchi M, Wang X, Andreoli AM, Leri A, Malhotra A, Kajstura J, Anversa P (1999) Insulin-like growth factor-1 attenuates the detrimental impact of nonocclusive coronary artery constriction on the heart. Circ Res 84(9):1007–1019
Welch S, Plank D, Witt S, Glascock B, Schaefer E, Chimenti S, Andreoli AM, Limana F, Leri A, Kajstura J, Anversa P, Sussman MA (2002) Cardiac-specific igf-1 expression attenuates dilated cardiomyopathy in tropomodulin-overexpressing transgenic mice. Circ Res 90(6):641–648
Colao A (2008) The gh-igf-i axis and the cardiovascular system: clinical implications. Clin Endocrinol (Oxf) 69(3):347–358. doi:CEN3292[pii]10.1111/j.1365-2265.2008.03292.x
Suleiman MS, Singh RJ, Stewart CE (2007) Apoptosis and the cardiac action of insulin-like growth factor i. Pharmacol Ther 114(3):278–294. doi:S0163-7258(07)00049-6[pii]10.1016/j.pharmthera.2007.03.001
Arnqvist HJ (2008) The role of igf-system in vascular insulin resistance. Horm Metab Res 40(9):588–592. doi:10.1055/s-0028-1082325
Smith TJ (2010) Insulin-like growth factor-i regulation of immune function: a potential therapeutic target in autoimmune diseases? Pharmacol Rev 62(2):199–236. doi:pr.109.002469[pii]10.1124/pr.109.002469
Higashi Y, Sukhanov S, Anwar A, Shai SY, Delafontaine P (2010) Igf-1, oxidative stress and atheroprotection. Trends Endocrinol Metab 21(4):245–254. doi:S1043-2760(09)00214-8[pii]10.1016/j.tem.2009.12.005
Sara VR, Hall K (1990) Insulin-like growth factors and their binding proteins. Physiol Rev 70(3):591–614
Pardee AB (1989) G1 events and regulation of cell proliferation. Science 246(4930):603–608
Pollak MN, Schernhammer ES, Hankinson SE (2004) Insulin-like growth factors and neoplasia. Nat Rev Cancer 4(7):505–518. doi:10.1038/nrc1387nrc1387[pii]
Werner H, Karnieli E, Rauscher FJ, LeRoith D (1996) Wild-type and mutant p53 differentially regulate transcription of the insulin-like growth factor i receptor gene. Proc Natl Acad Sci USA 93(16):8318–8323
LeRoith D, Yakar S (2007) Mechanisms of disease: metabolic effects of growth hormone and insulin-like growth factor 1. Nat Clin Pract Endocrinol Metab 3(3):302–310. doi:ncpendmet0427[pii]10.1038/ncpendmet0427
Mauras N, Haymond MW (2005) Are the metabolic effects of gh and igf-i separable? Growth Horm IGF Res 15(1):19–27. doi:S1096-6374(04)00172-8[pii]10.1016/j.ghir.2004.12.003
Yuen KC, Dunger DB (2007) Therapeutic aspects of growth hormone and insulin-like growth factor-i treatment on visceral fat and insulin sensitivity in adults. Diabetes Obes Metab 9(1):11–22. doi:DOM591[pii]10.1111/j.1463-1326.2006.00591.x
Camacho-Hubner C, Woods KA, Clark AJ, Savage MO (2002) Insulin-like growth factor (igf)-i gene deletion. Rev Endocr Metab Disord 3(4):357–361
Clemmons DR, Moses AC, McKay MJ, Sommer A, Rosen DM, Ruckle J (2000) The combination of insulin-like growth factor i and insulin-like growth factor-binding protein-3 reduces insulin requirements in insulin-dependent type 1 diabetes: evidence for in vivo biological activity. J Clin Endocrinol Metab 85(4):1518–1524
Clemmons DR, Moses AC, Sommer A, Jacobson W, Rogol AD, Sleevi MR, Allan G (2005) Rh/igf-i/rhigfbp-3 administration to patients with type 2 diabetes mellitus reduces insulin requirements while also lowering fasting glucose. Growth Horm IGF Res 15(4):265–274. doi:S1096-6374(05)00055-9[pii]10.1016/j.ghir.2005.05.002
Cusi K, DeFronzo R (2000) Recombinant human insulin-like growth factor i treatment for 1 week improves metabolic control in type 2 diabetes by ameliorating hepatic and muscle insulin resistance. J Clin Endocrinol Metab 85(9):3077–3084
Saukkonen T, Shojaee-Moradie F, Williams RM, Amin R, Yuen KC, Watts A, Acerini CL, Umpleby AM, Dunger DB (2006) Effects of recombinant human igf-i/igf-binding protein-3 complex on glucose and glycerol metabolism in type 1 diabetes. Diabetes 55(8):2365–2370. doi:55/8/2365[pii]10.2337/db05-1646
Henry RR, Abrams L, Nikoulina S, Ciaraldi TP (1995) Insulin action and glucose metabolism in nondiabetic control and niddm subjects. Comparison using human skeletal muscle cell cultures. Diabetes 44(8):936–946
Baudry A, Lamothe B, Bucchini D, Jami J, Montarras D, Pinset C, Joshi RL (2001) Igf-1 receptor as an alternative receptor for metabolic signaling in insulin receptor-deficient muscle cells. FEBS Lett 488(3):174–178. doi:S0014-5793(00)02435-2[pii]
Sakai K, Lowman HB, Clemmons DR (2002) Increases in free, unbound insulin-like growth factor i enhance insulin responsiveness in human hepatoma g2 cells in culture. J Biol Chem 277(16):13620–13627. doi:10.1074/jbc.M107771200M107771200[pii]
Ohlsson C, Mohan S, Sjogren K, Tivesten A, Isgaard J, Isaksson O, Jansson JO, Svensson J (2009) The role of liver-derived insulin-like growth factor-i. Endocr Rev 30(5):494–535. doi:er.2009-0010[pii]10.1210/er.2009-0010
DeChiara TM, Efstratiadis A, Robertson EJ (1990) A growth-deficiency phenotype in heterozygous mice carrying an insulin-like growth factor ii gene disrupted by targeting. Nature 345(6270):78–80. doi:10.1038/345078a0
Giannoukakis N, Deal C, Paquette J, Goodyer CG, Polychronakos C (1993) Parental genomic imprinting of the human igf2 gene. Nat Genet 4(1):98–101. doi:10.1038/ng0593-98
Ren H, Yin P, Duan C (2008) Igfbp-5 regulates muscle cell differentiation by binding to igf-ii and switching on the igf-ii auto-regulation loop. J Cell Biol 182(5):979–991. doi:jcb.200712110[pii]10.1083/jcb.200712110
Reeve AE, Eccles MR, Wilkins RJ, Bell GI, Millow LJ (1985) Expression of insulin-like growth factor-ii transcripts in wilms’ tumour. Nature 317(6034):258–260
Lammers R, Gray A, Schlessinger J, Ullrich A (1989) Differential signalling potential of insulin- and igf-1-receptor cytoplasmic domains. EMBO J 8(5):1369–1375
Shymko RM, Dumont E, De Meyts P, Dumont JE (1999) Timing-dependence of insulin-receptor mitogenic versus metabolic signalling: a plausible model based on coincidence of hormone and effector binding. Biochem J 339(Pt 3):675–683
Louvi A, Accili D, Efstratiadis A (1997) Growth-promoting interaction of igf-ii with the insulin receptor during mouse embryonic development. Dev Biol 189(1):33–48. doi:S0012-1606(97)98666-8[pii]10.1006/dbio.1997.8666
Mynarcik DC, Williams PF, Schaffer L, Yu GQ, Whittaker J (1997) Identification of common ligand binding determinants of the insulin and insulin-like growth factor 1 receptors. Insights into mechanisms of ligand binding. J Biol Chem 272(30):18650–18655
Zelobowska K, Gumprecht J, Grzeszczak W (2009) Mitogenic potency of insulin glargine. Endokrynol Pol 60(1):34–39
Schwartz GP, Burke GT, Katsoyannis PG (1987) A superactive insulin: [b10-aspartic acid]insulin(human). Proc Natl Acad Sci USA 84(18):6408–6411
Bornfeldt KE, Gidlof RA, Wasteson A, Lake M, Skottner A, Arnqvist HJ (1991) Binding and biological effects of insulin, insulin analogues and insulin-like growth factors in rat aortic smooth muscle cells. Comparison of maximal growth promoting activities. Diabetologia 34(5):307–313
Drejer K (1992) The bioactivity of insulin analogues from in vitro receptor binding to in vivo glucose uptake. Diabetes Metab Rev 8(3):259–285
Milazzo G, Sciacca L, Papa V, Goldfine ID, Vigneri R (1997) Aspb10 insulin induction of increased mitogenic responses and phenotypic changes in human breast epithelial cells: evidence for enhanced interactions with the insulin-like growth factor-i receptor. Mol Carcinog 18(1):19–25. doi:10.1002/(SICI)1098-2744(199701)18:1<19:AID-MC3>3.0.CO;2-M[pii]
Hansen BF, Danielsen GM, Drejer K, Sorensen AR, Wiberg FC, Klein HH, Lundemose AG (1996) Sustained signalling from the insulin receptor after stimulation with insulin analogues exhibiting increased mitogenic potency. Biochem J 315(Pt 1):271–279
Pollak M, Russell-Jones D (2010) Insulin analogues and cancer risk: cause for concern or cause celebre? Int J Clin Pract 64(5):628–636. doi:IJCP2354[pii]10.1111/j.1742-1241.2010.02354.x
Bahr M, Kolter T, Seipke G, Eckel J (1997) Growth promoting and metabolic activity of the human insulin analogue [glya21, argb31, argb32]insulin (hoe 901) in muscle cells. Eur J Pharmacol 320(2–3):259–265. doi:S0014-2999(96)00903-X[pii]
Chisalita SI, Arnqvist HJ (2004) Insulin-like growth factor i receptors are more abundant than insulin receptors in human micro- and macrovascular endothelial cells. Am J Physiol Endocrinol Metab 286(6):E896–E901. doi:10.1152/ajpendo.00327.200300327.2003[pii]
Ciaraldi TP, Carter L, Seipke G, Mudaliar S, Henry RR (2001) Effects of the long-acting insulin analog insulin glargine on cultured human skeletal muscle cells: comparisons to insulin and igf-i. J Clin Endocrinol Metab 86(12):5838–5847
Kurtzhals P, Schaffer L, Sorensen A, Kristensen C, Jonassen I, Schmid C, Trub T (2000) Correlations of receptor binding and metabolic and mitogenic potencies of insulin analogs designed for clinical use. Diabetes 49(6):999–1005
Shukla A, Grisouard J, Ehemann V, Hermani A, Enzmann H, Mayer D (2009) Analysis of signaling pathways related to cell proliferation stimulated by insulin analogs in human mammary epithelial cell lines. Endocr Relat Cancer 16(2):429–441. doi:ERC-08-0240[pii]10.1677/ERC-08-0240
Weinstein D, Simon M, Yehezkel E, Laron Z, Werner H (2009) Insulin analogues display igf-i-like mitogenic and anti-apoptotic activities in cultured cancer cells. Diabetes Metab Res Rev 25(1):41–49. doi:10.1002/dmrr.912
Mayer D, Chantelau E (2010) Treatment with insulin glargine (lantus) increases the proliferative potency of the serum of patients with type-1 diabetes: a pilot study on mcf-7 breast cancer cells. Arch Physiol Biochem 116(2):73–78. doi:10.3109/13813451003631439
Berti L, Kellerer M, Bossenmaier B, Seffer E, Seipke G, Haring HU (1998) The long acting human insulin analog hoe 901: characteristics of insulin signalling in comparison to asp(b10) and regular insulin. Horm Metab Res 30(3):123–129. doi:10.1055/s-2007-978849
Staiger K, Staiger H, Schweitzer MA, Metzinger E, Balletshofer B, Haring HU, Kellerer M (2005) Insulin and its analogue glargine do not affect viability and proliferation of human coronary artery endothelial and smooth muscle cells. Diabetologia 48(9):1898–1905. doi:10.1007/s00125-005-1874-4
Erbel S, Reers C, Eckstein VW, Kleeff J, Buchler MW, Nawroth PP, Ritzel RA (2008) Proliferation of colo-357 pancreatic carcinoma cells and survival of patients with pancreatic carcinoma are not altered by insulin glargine. Diabetes Care 31(6):1105–1111. doi:dc07-2015[pii]10.2337/dc07-2015
Staiger K, Hennige AM, Staiger H, Haring HU, Kellerer M (2007) Comparison of the mitogenic potency of regular human insulin and its analogue glargine in normal and transformed human breast epithelial cells. Horm Metab Res 39(1):65–67. doi:10.1055/s-2007-957352
Liefvendahl E, Arnqvist HJ (2008) Mitogenic effect of the insulin analogue glargine in malignant cells in comparison with insulin and igf-i. Horm Metab Res 40(6):369–374. doi:10.1055/s-2008-1062739
Stammberger I, Bube A, Durchfeld-Meyer B, Donaubauer H, Troschau G (2002) Evaluation of the carcinogenic potential of insulin glargine (lantus) in rats and mice. Int J Toxicol 21(3):171–179. doi:10.1080/10915810290096306
Eckardt K, May C, Koenen M, Eckel J (2007) Igf-1 receptor signalling determines the mitogenic potency of insulin analogues in human smooth muscle cells and fibroblasts. Diabetologia 50(12):2534–2543. doi:10.1007/s00125-007-0815-9
Author information
Authors and Affiliations
Division of Endocrinology, Diabetology and Metabolism, Department of Internal Medicine, University of Turin, Corso Dogliotti 14, 10126, Turin, Italy
Marta Annunziata, Riccarda Granata & Ezio Ghigo
- Marta Annunziata
Search author on:PubMed Google Scholar
- Riccarda Granata
Search author on:PubMed Google Scholar
- Ezio Ghigo
Search author on:PubMed Google Scholar
Corresponding author
Correspondence toEzio Ghigo.
Rights and permissions
About this article
Cite this article
Annunziata, M., Granata, R. & Ghigo, E. The IGF system.Acta Diabetol48, 1–9 (2011). https://doi.org/10.1007/s00592-010-0227-z
Received:
Accepted:
Published:
Issue date:
Share this article
Anyone you share the following link with will be able to read this content:
Sorry, a shareable link is not currently available for this article.
Provided by the Springer Nature SharedIt content-sharing initiative

