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.
Similar content being viewed by others
Abbreviations
- ACTH:
-
Adrenocorticotropic hormone
- HS:
-
Horse serum
- FCS:
-
Fetal calf serum
- IGF:
-
Insulin-like growth factor
- PBS:
-
Phosphate buffer saline
References
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
Alport BS (1984) Steroid-induced hypertrophic cardiomyopathy in an infant. Pediatr Cardiol 5:117–118
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
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
Battaglia FC, Meschia G (1978) Substrates of fetal metabolism. Physiol Rev 58:499–527.
Breitweser JA, Meyer RA, Sperling MA, Tsang RC, Kaplan S (1980) Cardiac septal hypertrophy in hyperinsulinemic infants. J Pediatr 96:535–539
D'Ercole AJ, Applewhite GT, Underwood LE (1980) Evidence that somatomedin is synthesized by multiple tissues in the fetus. Dev Biol 75:315–318
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
Froesch ER, Zapf J (1985) Insulin-like growth factors and insulin: comparative aspects. Diabetologia 28:485–494
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
Gutgesell HP, Speer ME, Rosenberg HS (1979) Characterization of the cardiomyopathy in infants of diabetic mothers. Circulation 61:441–451
Haider W, Eckersberger F, Losert U, Wolner E (1982) Erhöhte Myokardprotektion in der offenen Herzchirurgie durch massive präoperative Insulinzufuhr. Anaesthesist 31:124–128
Haworth RA, Hunter DR, Berkoff HA (1984) Heterogenous response of isolated adult rat heart cells to insulin. Arch Biochem Biophys 233:105–114
Hirsch HJ, Loo S, Evans N (1977) Hypoglycemia of infancy and nesidioblastosis. Studies with somatostatin. N Engl J Med 296:1323–1326
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
Lee JC, Downing SE (1976) Effects of insulin on cardiac muscle concentration and responsiveness to norepinephrine. Am J Physiol 230:1360–1365
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
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
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
Milley JR (1986) The effect of chronic hyperinsulinemia on ovine fetal growth. Growth 50:390–401
Moolenaar WH, Tertoolen LGJ, deLaat SW (1984) Growth factors immediately raise cytoplasmic free Ca2+ in human fibroblasts. J Biol Chem 259:8066–8068
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
Pentz S, Hörler H (1988) Herzmuskelzellen der Ratte — ein in vitro Testsystem. In: Maurer MR (ed) Zellkulturmethoden. Thieme Verlag, Stuttgart, in press
Rechler MM, Nissley SP (1985) The nature and regulation of the receptors for insulin-like growth factors. Ann Res Physiol 47:425–442
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
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
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
Shah OK, Verma SC (1980) The cardiac inotropic responses to insulin in the rat heart. Indian J Physiol Pharmacol 24:346–350
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
Vetter U, Teller WM (1985) Somatomedine und ihre Bedeutung für die Pädiatrie. Klin Pädiat 197:378–385
Author information
Authors and Affiliations
Additional information
Dedicated to Prof. Dr. W. M. Teller on the occasion of his 60th birthday
Rights and permissions
About this article
Cite this article
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
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF01906959