Skip to main content
Log in

Insulin-Like Growth Factor I

An Attractive Option for Chronic Heart Failure?

  • Leading Article
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Abstract

Chronic congestive heart failure is a syndrome with a poor prognosis. Currently, the only therapy providing the possibility of long term survival is heart transplantation. Therefore, new therapeutic strategies continue to be investigated. One such new approach may be the application of recombinant human insulin-like growth factor (IGF)-1. IGF-1 has both acute and long term cardiovascular effects. Acute administration of IGF-1 resulted in a reduction in afterload and positive inotropic effects in patients with heart failure. In vitro and animal studies have demonstrated that IGF-1 can stimulate myofibril formation. In addition, IGF-1 administration has beneficial metabolic effects. The benefits of prolonged IGF-1 therapy have yet to be investigated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Froesch ER, Guler HP, Schmid CH, et al. Insulin-like growth factors. In: Rifkin H, Porte D, editors. Ellenberg and Rifkin’s diabetes mellitus: theory and practice. 4th ed. New York: Elsevier, 1990: 154–64

    Google Scholar 

  2. Florini JR, Ewton DZ. Induction of gene expression in muscle by the IGFs. Growth Regul 1992; 2: 23–9

    PubMed  CAS  Google Scholar 

  3. Ito H, Hiroe M, Hirata Y, et al. Insulin-like growth factor-I induces hypertrophy with enhanced expression of muscle specific genes in cultured rat cardiomyocytes. Circulation 1993; 87: 1715–21

    Article  PubMed  CAS  Google Scholar 

  4. Donath MY, Zapf J, Eppenberger-Eberhardt M, et al. Insulinlike growth factor I stimulates myofibril development and decreases smooth muscle alpha actin of adult cardiomyocytes. Proc Natl Acad Sci USA 1994; 91: 1686–90

    Article  PubMed  CAS  Google Scholar 

  5. Harder BA, Schaub MC, Eppenberger HM, et al. Influence of fibroblast growth factor (bFGF) and insulin-like growth factor (IGF-I) on cytoskeletal and contractile structures and on atrial natriuretic factor (ANF) expression in adult rat cardiomyocytes culture. J Mol Cell Cardiol 1996; 28: 19–31

    Article  PubMed  CAS  Google Scholar 

  6. Guler H-P, Zapf J, Scheiwiller E, et al. Recombinant human insulin-like growth factor I stimulates growth and has distinct effects on organ size in hypophysectomized rats. Proc Natl Acad Sci U S A 1988; 85: 4889–93

    Article  PubMed  CAS  Google Scholar 

  7. Donath, MY, Gosteli-Peter MA, Hauri C, et al. Insulin-like growth factor I stimulate myofibrillar genes and modulates atrial natriuretic factor mRNA in rat heart. Eur J Endocrinol 1997; 137: 309–15

    Article  PubMed  CAS  Google Scholar 

  8. Forman MB, Puett DW, Virmani R. Endothelial and myocardial injury during ischemia and reperfusion: pathogenesis and therapeutic implications. J Am Coll Cardiol 1989; 13: 450–9

    Article  PubMed  CAS  Google Scholar 

  9. Gottlieb RA, Burleson KO, Kloner RA, et al. Reperfusion in jury induces apoptosis in rabbit cardiomyocytes. J Clin Invest 1994; 94: 1621–8

    Article  PubMed  CAS  Google Scholar 

  10. Rodriguez-Tarduchy G, Collins MK, Garcia I, et al. Insulin-like growth factor I inhibits apoptosis in IL-3-dependent hemopoietic cells. J Immunol 1992; 149: 535–40

    PubMed  CAS  Google Scholar 

  11. Muta K, Krantz SB. Apoptosis of human erythroid colonyforming cells is decreased by stem cell factor and insulin-like growth factor I as well as erythropoietin. J Cell Physiol 1993; 156: 264–74

    Article  PubMed  CAS  Google Scholar 

  12. Muta K, Krantz SB, Bondurant MC, et al. Distinct roles of erythropoietin, insulin-like growth factor I, and stem cell factor in the development of erythroid progenitor cells. J Clin Invest 1994; 94: 34–43

    Article  PubMed  CAS  Google Scholar 

  13. Gluckman BD, Guan J, Beilharz EJ, et al. The role of the insulin-like growth factor system in neuronal rescue. Ann NY Acad Sci 1994; 138: 148

    Google Scholar 

  14. Neff NT, Perevette D, Houenou LJ, et al. Insulin-like growth factors: putative muscle-derived trophic agents that promote motoneuron survival. J Neurobiol 1993; 24: 1578–88

    Article  PubMed  CAS  Google Scholar 

  15. Christofori G, Naik B, Hanahan D. A second signal supplied by insulin-like growth factor II in oncogene-induced tumorigenesis. Nature 1994; 369: 414–7

    Article  PubMed  CAS  Google Scholar 

  16. Resnicoff M, Abraham D, Yutanawiboonchai W, et al. The insulin-like growth factor I receptor protects tumor cells from apoptosis in vivo. Cancer Res 1995; 55: 2463–9

    PubMed  CAS  Google Scholar 

  17. Wu X, Fan Z, Masui H, et al. Apoptosis induced by an anti-epidermal growth factor receptor monoclonal antibody in a human colorectal carcinoma cell line and its delay by insulin. J Clin Invest 1995; 95: 1897–905

    Article  PubMed  CAS  Google Scholar 

  18. Bennett MR, Evan GI, Schwartz SM. Apoptosis of human vascular smooth muscle cells derived from normal vessels and coronary arteriosclerotic plaques. J Clin Invest 1995; 95: 2266–74

    Article  PubMed  CAS  Google Scholar 

  19. Buerke M, Murohara T, Skurk C, et al. Cardioprotective effect of insulin-like growth factor I in myocardial ischemia followed by reperfusion. Proc Natl Acad Sci U S A 1995; 92: 8031–35

    Article  PubMed  CAS  Google Scholar 

  20. Ambler GR, Johnston BM, Maxwell L, et al. Improvement of doxorubicin induced cardiomyopathy in rats treated with insulin-like growth factor I. Cardiovasc Res 1993; 27: 1368–73

    Article  PubMed  CAS  Google Scholar 

  21. Duerr RL, McKirnan MD, Gim RD, et al. Cardiovascular effects of insulin-like growth factor-1 and growth hormone in chronic left ventricular failure in the rat. Circulation 1996; 93: 2188–96

    Article  PubMed  CAS  Google Scholar 

  22. Vetter U, Kupferschmid C, Lang D, et al. Insulin-like growth factors and insulin increase the contractility of neonatal rat cardiocytes in vitro. Basic Res Cardiol 1988; 83: 647–54

    Article  PubMed  CAS  Google Scholar 

  23. Johnston DM, Gluckman PD, Bratt CM, et al. Insulin-like growth factors elicit positive inotropic responses in isolated rat heart [abstract]. Growth Regul 1994; 4: 44

    Google Scholar 

  24. Freestone NS, Ribaric S, Mason WT. The effect of insulin-like growth factor-1 on adult rat cardiac contractility. Mol Cell Biochem 1996; 163–164: 223–9

    Article  PubMed  Google Scholar 

  25. Copland AC, Nair KS. Recombinant human insulin-like growth factor I increases forearm blood flow. J Clin Endocrinol Metab 1994; 79: 230–2

    Article  Google Scholar 

  26. Fryburg DA. IGF-I exerts GH and insulin-like actions on human muscle protein metabolism. Am J Physiol 1994; 267: E331–6

    PubMed  CAS  Google Scholar 

  27. Kiowski W, Stoschitsky K, Kim JH, et al. Insulin-like growth factor-I causes endothelium-dependent arterial vasodilatation [abstract]. Circulation 1994; 90: 1–242

    Article  Google Scholar 

  28. Russell-Jones DL, Bates AT, Umpleby AM, et al. Acomparison of the effects of IGF-I and insulin on glucose metabolism, fat metabolism and the cardiovascular system in normal human volunteers. Eur J Clin Invest 1995; 25: 403–11

    Article  PubMed  CAS  Google Scholar 

  29. Donath MY, Jenni R, Brunner HP, et al. Cardiovascular and metabolic effects of insulin-like growth factor I at rest and during exercise in humans. J Clin Endocrinol Metab 1996; 81: 4089–94

    Article  PubMed  CAS  Google Scholar 

  30. Donath MY, Sütsch G, Yan XW, et al. Acute cardiovascular effects of insulin-like growth factor I in patients with chronic heart failure. J Clin Endocrinol Metab 1998; 83: 3177–83

    Article  PubMed  CAS  Google Scholar 

  31. Daughaday WH, Hall K, Raben MS, et al. Somatomedin: proposed designation for sulphation factor. Nature 1972; 235: 107

    Article  PubMed  CAS  Google Scholar 

  32. Schoenle E, Zapf J, Humbel RE, et al. Insulin-like growth factor I stimulates growth in hypophysectomized rats. Nature 1982; 296: 252–3

    Article  PubMed  CAS  Google Scholar 

  33. Courville C, Mason VR. The heart in acromegaly. Arch Intern Med 1938; 61: 704–13

    Article  Google Scholar 

  34. Wright AD, Hill DM, Lowy C, et al. Mortality in acromegaly. Q J Med 1970; 39: 1–16

    PubMed  CAS  Google Scholar 

  35. Cuneo RC, Salomon F, Wilmshurst P, et al. Cardiovascular effects of growth hormone treatment in growth hormone-deficient adults: stimulation of the renin-aldosterone system. Clin Sci 1991 81: 587–92

    PubMed  CAS  Google Scholar 

  36. Merola B, Cittadini A, Colao A, et al. Cardiac structural and functional abnormalities in adult patients with growth hormone deficiency. J Clin Endocrinol Metab 1993; 77: 1658–61

    Article  PubMed  CAS  Google Scholar 

  37. Amato G, Carella C, Fazio S, et al. Body composition, bone metabolism, heart structure and function in growth hormone-deficient adults before and after growth hormone replacement therapy at low doses. J Clin Endocrinol Metab 1993; 77: 1671–6

    Article  PubMed  CAS  Google Scholar 

  38. Fazio S, Sabatini D, Capaldo B, et al. A preliminary study of growth hormone in the treatment of dilated cardiomyopathy. N Engl J Med 1996; 334: 809–14

    Article  PubMed  CAS  Google Scholar 

  39. Genth-Zotz S, Zotz R, Geil S, et al. Recombinant growth hormone therapy in patients with ischemic cardiomyopathy: effects on hemodynamics, left ventricular function, and cardiopulmonary exercise capacity. Circulation 1999; 99: 18–21

    Article  PubMed  CAS  Google Scholar 

  40. Flyvbjerg A, Jørgensen KD, Marshall SM, et al. Inhibitory effect of octreotide on growth hormone-induced IGF-I generation and organ growth in hypophysectomized rats. Am J Physiol 1991; 260: E568–74

    PubMed  CAS  Google Scholar 

  41. Isgaard J, Nilsson A, Vikman K, et al. Growth hormone regulates the level of insulin-like growth factor I mRNA in rat skeletal muscle. J Endocrinol 1989; 120: 107–2

    Article  PubMed  CAS  Google Scholar 

  42. Gosteli-Peter MA, Winterhalter KH, Schmid C, et al. Expression and regulation of insulin-like growth factor I (IGF-I) and IGF binding protein messenger ribonucleic acid levels in tissues of hypophysectomized rats infused with IGF-I and growth hormone. Endocrinology 1994; 135: 2558–67

    Article  PubMed  CAS  Google Scholar 

  43. McGuffin Jr WL, Sherman BM, Roth J, et al. Acromegaly and cardiovascular disorders. A prospective study. Ann Intern Med 1974; 81: 11–8

    PubMed  Google Scholar 

  44. Martins JB, Kerber RE, Sherman BM, et al. Cardiac function in acromegaly. Circulation 1977; 56: 863–69

    Article  PubMed  CAS  Google Scholar 

  45. Møller N, Schmitz O, Jørgensen JOL, et al. Basal and insulin-stimulated substrate metabolism in patients with active acromegaly before and after adenomectomy. J Clin Endocrinol Metab 1992; 74: 1012–9

    Article  PubMed  Google Scholar 

  46. Nikkila EA, Pelkonen R. 1975 Serum lipids in acromegaly. Metabolism 1975; 24: 829–38

    Article  PubMed  CAS  Google Scholar 

  47. Guler H-P, Schmid C, Zapf J, et al. Effects of recombinant insulin-like growth factor I on insulin secretion and renal function in normal human subjects. Proc Natl Acad Sci U S A 1989; 86: 2868–72

    Article  PubMed  CAS  Google Scholar 

  48. Zenobi PD, Graf S, Ursprung H, et al. Effects of insulin-like growth factor I on glucose tolerance, insulin levels and insulin secretion. J Clin Invest 1992; 89: 1908–13

    Article  PubMed  CAS  Google Scholar 

  49. Hussain MA, Schmitz O, Mengel A, et al. Insulin-like growth factor I stimulates lipid oxidation, reduces protein oxidation and enhances insulin sensitivity in humans. J Clin Invest 1993; 92: 2249–56

    Article  PubMed  CAS  Google Scholar 

  50. Froesch ER, Hussain MA. Recombinant human insulin-like growth factor-I: a therapeutic challenge for diabetes mellitus. Diabetologia 1994; 37: 179–85

    Article  Google Scholar 

  51. Zenobi PD, Holzmann P, Glatz Y, et al. Improvement of lipid profile in type 2 (non-insulin-dependent) diabetes mellitus by insulin-like growth factor I. Diabetologia 1993; 36: 465–69

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Marc Y. Donath.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Donath, M.Y., Zapf, J. Insulin-Like Growth Factor I. Drugs Aging 15, 251–254 (1999). https://doi.org/10.2165/00002512-199915040-00001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002512-199915040-00001

Keywords

Navigation