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Insulin-like growth factors and insulin increase the contractility of neonatal rat cardiocytes in vitro

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Summary

In the newborn several situations of hyperinsulinism can be associated with myocardial hypertrophy and increased contractility. Insulin and the insulin-like growth factors (IGF) are derived from a common ancestral molecule. Insulin exerts mainly metabolic action, whereas the IGFs promote cell multiplication and differentiation.

Using an assay system of cultured neonatal myocardial cells the stimulatory action of insulin and the insulin-like growth factors I and II on myocardial cell contractility was investigated. Spontaneously beating aggregates of myocardial cells were synchronized by an electric impulse generator. Contractility was measured via the amplitude of contraction by an optoelectronic system. Insulin at a concentration of 6,250 and 12,500 μU/ml increased the contractility by 11 and 18%; IGF-I at a concentration of 12 and 25 ng/ml, and IGF-II at a concentration of 25 and 50 ng/ml increased the contractility by 16 and 22%, and 13 and 18%, respectively. Lower concentrations did not provoke a significant increase in contractility.

Insulin only in supraphysiological doses increases the contractility of neonatal myocardial rat cells, whereas both insulin-like growth factors act in physiological concentrations. Therefore, during hyperinsulinism insulin may increase myocardial contractility via the IGF receptor and not via the insulin receptor.

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Abbreviations

ACTH:

Adrenocorticotropic hormone

HS:

Horse serum

FCS:

Fetal calf serum

IGF:

Insulin-like growth factor

PBS:

Phosphate buffer saline

References

  1. Almira EC, Garcia AR, Bohell BR (1986) Insulin binding and glucose transport activity in cardiomyocytes of a diabetic rat. Am J Physiol 250 E:402–406

    Google Scholar 

  2. Alport BS (1984) Steroid-induced hypertrophic cardiomyopathy in an infant. Pediatr Cardiol 5:117–118

    PubMed  Google Scholar 

  3. Apstein CS, Gravino FN, Handerschild CC (1983) Determinant of a protective effect of glucose and insulin on the ischemic myocardium. Effects on contractile function, diastolic compliance, metabolism and ultrastructure during ischemia and reperfusion. Circ Res 52:515–526

    PubMed  Google Scholar 

  4. Balk SD, Morisi A, Gunter HS, Svoboda MF, van Wyk JJ, Nissley SP, Sanes CG (1984) Somatomedins (IGFs) but not growth hormone are mitogenic for chicken heart mesenchymal cells and act synergistically with EGF and brain FGF. Life Sciences 35:335–346

    Article  PubMed  Google Scholar 

  5. Battaglia FC, Meschia G (1978) Substrates of fetal metabolism. Physiol Rev 58:499–527.

    PubMed  Google Scholar 

  6. Breitweser JA, Meyer RA, Sperling MA, Tsang RC, Kaplan S (1980) Cardiac septal hypertrophy in hyperinsulinemic infants. J Pediatr 96:535–539

    PubMed  Google Scholar 

  7. D'Ercole AJ, Applewhite GT, Underwood LE (1980) Evidence that somatomedin is synthesized by multiple tissues in the fetus. Dev Biol 75:315–318

    Article  PubMed  Google Scholar 

  8. Eckel J, van Echten G, Reinauer H (1985) Adult cardiac myocytes in primary culture: cell characteristics and insulin receptor interaction. Am J Physiol 249,4:212–221

    Google Scholar 

  9. Froesch ER, Zapf J (1985) Insulin-like growth factors and insulin: comparative aspects. Diabetologia 28:485–494

    Article  PubMed  Google Scholar 

  10. Gibbons WR (1986) Cellular control of cardiac contraction. In: Fozzard HA (ed) Cellular control of cardiac contraction (vol I). Raven Press, New York, pp 747–778

    Google Scholar 

  11. Gutgesell HP, Speer ME, Rosenberg HS (1979) Characterization of the cardiomyopathy in infants of diabetic mothers. Circulation 61:441–451

    Google Scholar 

  12. Haider W, Eckersberger F, Losert U, Wolner E (1982) Erhöhte Myokardprotektion in der offenen Herzchirurgie durch massive präoperative Insulinzufuhr. Anaesthesist 31:124–128

    PubMed  Google Scholar 

  13. Haworth RA, Hunter DR, Berkoff HA (1984) Heterogenous response of isolated adult rat heart cells to insulin. Arch Biochem Biophys 233:105–114

    Article  Google Scholar 

  14. Hirsch HJ, Loo S, Evans N (1977) Hypoglycemia of infancy and nesidioblastosis. Studies with somatostatin. N Engl J Med 296:1323–1326

    PubMed  Google Scholar 

  15. Lang D, Mühler E, Kupferschmid Ch, Tacke E, v Bernuth G (1984) Cardiac hypertrophy secondary to ACTH treatment in children. Eur J Pediatr 142:121–125

    Article  PubMed  Google Scholar 

  16. Lee JC, Downing SE (1976) Effects of insulin on cardiac muscle concentration and responsiveness to norepinephrine. Am J Physiol 230:1360–1365

    PubMed  Google Scholar 

  17. Markovitz LJ, Hasin Y, Freund HR (1985) The effect of insulin and glucagon on systolic properties of the normal and septic isolated rat heart. Basic Res Cardiol 80:377–383

    PubMed  Google Scholar 

  18. Meuli C, Froesch ER (1975) Effects of insulin and of NSIL A-S on the perfused rat heart: glucose uptake, lactate production and effect of 3-O-methyl glucose. Eur J Clin Invest 5:93–99

    PubMed  Google Scholar 

  19. Meuli C, Froesch ER (1976) Binding of insulin and nonsuppressible insulin-like activity to isolated perfused rat heart muscle. Arch Biochem Biophys 177:31–38

    Article  PubMed  Google Scholar 

  20. Milley JR (1986) The effect of chronic hyperinsulinemia on ovine fetal growth. Growth 50:390–401

    PubMed  Google Scholar 

  21. Moolenaar WH, Tertoolen LGJ, deLaat SW (1984) Growth factors immediately raise cytoplasmic free Ca2+ in human fibroblasts. J Biol Chem 259:8066–8068

    PubMed  Google Scholar 

  22. Pedersen J, Molstedt-Pedersen L (1970) The hyperglycemia-hyperinsulinism theory and the weight of the newborn baby. In: Rodriguez VO (ed) JCS 231. Excerpta Medica, Amsterdam, pp 678–685

    Google Scholar 

  23. Pentz S, Hörler H (1988) Herzmuskelzellen der Ratte — ein in vitro Testsystem. In: Maurer MR (ed) Zellkulturmethoden. Thieme Verlag, Stuttgart, in press

    Google Scholar 

  24. Rechler MM, Nissley SP (1985) The nature and regulation of the receptors for insulin-like growth factors. Ann Res Physiol 47:425–442

    Article  Google Scholar 

  25. Reikeras O, Gunnes P, Sorlie D, Ekroth R, Mjos OD (1986) Hemodynamic effects of insulin and β-receptor blockade during acute left ventricular failure in dogs. Eur Heart J 7:227–233

    PubMed  Google Scholar 

  26. Rinderknecht E, Humbel R (1976) Polypeptides with nonsuppressive insulin-like and cell growth promoting activities in human serum. Isolation, chemical characterization and some biological properties of form I and II. Proc Natl Acad Sci USA 73:2365–2370

    PubMed  Google Scholar 

  27. Schroedl NA, Hartzell CR, Ross PD, McCarl RL (1982) Glucose metabolism, insulin effects and developmental age of cultured neonatal rat heart cells. J Cell Physiol 113:231–239

    Article  PubMed  Google Scholar 

  28. Shah OK, Verma SC (1980) The cardiac inotropic responses to insulin in the rat heart. Indian J Physiol Pharmacol 24:346–350

    PubMed  Google Scholar 

  29. Susa JB, Neave C, Sehgal P, Singer DB, Zeller WP, Schwartz R (1984) Chronic hyperinsulinemia in the fetal rhesus monkey. Effects of physiological hyperinsulinemia on fetal growth and composition. Diabetes 33:656–660

    PubMed  Google Scholar 

  30. Vetter U, Teller WM (1985) Somatomedine und ihre Bedeutung für die Pädiatrie. Klin Pädiat 197:378–385

    Google Scholar 

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Author notes

  1. U. Vetter

    Present address: Universitätskinderklinik, Prittwitzstr. 43, 7900, Ulm/Donau

Authors and Affiliations

  1. Department of Pediatrics and of Clinical Genetics, University of Ulm, F.R.G.

    S. Pentz

Authors
  1. U. Vetter
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  2. C. Kupferschmid
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  3. D. Lang
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  4. S. Pentz
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Additional information

Dedicated to Prof. Dr. W. M. Teller on the occasion of his 60th birthday

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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 83, 647–654 (1988). https://doi.org/10.1007/BF01906959

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  • DOI: https://doi.org/10.1007/BF01906959

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