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The Hormone-Modulatory Effects of Adenosine in Skeletal Muscle

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Topics and Perspectives in Adenosine Research

Summary

The interactive effects of insulin and the local hormone adenosine have been investigated in vitro in a number of skeletal muscle preparations. Insulin affects carbohydrate metabolism in these preparations by stimulating the rate of glucose transport and increasing the rate of glyco-gen synthesis. The concentration of insulin necessary to stimulate the rates of both these processes half-maximally is 100 μU/ml. Removal of endogenously produced adenosine by addition of adenosine deaminase increased specifically the sensitivity of the rate of glucose transport to insulin, whilst exerting no effect on the rate of glycogen synthesis. This suggests that the molecular basis of such a modulatory effect is at the “post-receptor” level. This was observed in soleus muscle (90% type I fibres) and extensor digitorum longus (90% type II fibres), but not in hemi-diaphragm. The insulin-modulatory effect of endogenous adenosine could be mimicked in a predictable manner by addition of adenosine-receptor agonists or antagonists. The possibility that adenosine was exerting this novel action on glucose metabolism in skeletal muscle by changes in intracellular cyclic AMP concentration has been studied. Our results suggest that this is unlikely; adenosine-receptor agonists have a weak stimulatory effect on adenylate cyclase and, in addition, elevation of intracellular cyclic AMP concentrations either by addition of dibutyryl cyclic AMP or β-adrenoceptor agonists do not directly affect the sensitivity of the rate of glucose transport to insulin.

The possible pathophysiological role of the hormone-modulatory action of adenosine is discussed.

We thank the British Diabetic Association for financial support. FJL is a Commonwealth Commission Research Scholar and BL is supported by the British Medical Research Council.

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References

  1. Armstrong RB, Laughlin MH (1983) Bloodflows within and among rat muscles as a function of time during high-speed treadmill exercise. J Physiol (Lond) 344:189–208

    PubMed  CAS  Google Scholar 

  2. Belloni FL, Phair RD, Sparks HV (1979) The role of adenosine in prolonged vasodilation following flow-restricted exercise of canine skeletal muscle. Circ Res 44:759–766

    PubMed  CAS  Google Scholar 

  3. Berne RM (1963) Cardiac nucleotides in hypoxia: a possible role in regulation of coronary bloodflow. Am J Physiol 204:317–322

    PubMed  CAS  Google Scholar 

  4. Berne RM (1980) The role of adenosine in the regulation of coronary bloodflow. Circ Res 47:807–813

    PubMed  CAS  Google Scholar 

  5. Bockman EL, Berne RM, Rubio R (1976) Adenosine and active hyperaemia in dog skeletal muscle. Am J Physiol 230:1531–1537

    PubMed  CAS  Google Scholar 

  6. Budohoski L, Challiss RAJ, McManus B, Newsholme EA (1984) Effects of analogues of adenosine and methylxanthines on insulin sensitivity in soleus muscle of the rat. FEBS Lett 167:1–4

    Article  PubMed  CAS  Google Scholar 

  7. Budohoski L, Challiss RAJ, Lozeman FJ, McManus B, Newsholme EA (1984) Increased insulin sensitivity in soleus muscle from cold-exposed rats: reversal by an adenosine-receptor agonist. FEBS Lett 175:402–406

    Article  PubMed  CAS  Google Scholar 

  8. Budohoski L, Challiss RAJ, Cooney GJ, McManus B, Newsholme EA (1984) Reversal of dietary-induced insulin resistance in muscle of the rat by adenosine deaminase and an adenosine-receptor antagonist. Biochem J 224:327–330

    PubMed  CAS  Google Scholar 

  9. Challiss RAJ, Espinal J, Newsholme EA (1983) Insulin sensitivity of rates of glycolysis and glycogen synthesis in soleus, epitrochlearis and hemi-diaphragm muscles of the rat. Biosci Rep 3:675–679

    Article  PubMed  CAS  Google Scholar 

  10. Challiss RAJ, Budohoski L, McManus B, Newsholme EA (1984) Effects of an adenosine-receptor antagonist on insulin resistance in soleus muscle from obese Zucker rats. Biochem J 221:915–917

    Google Scholar 

  11. Challiss RAJ, Lozeman FJ, Leighton B, Newsholme EA (1986) Effects of the /?-adrenoceptor agonist isoprenaline on insulin sensitivity in soleus muscle of the rat. Biochem J 233:377–381

    PubMed  CAS  Google Scholar 

  12. Cohen P (1985) The role of protein phosphorylation in the hormonal control of enzyme activity. Eur J Biochem 151:439–448

    Article  PubMed  CAS  Google Scholar 

  13. Crettaz M, Prentki M, Zaninetti D, Jeanrenaud B (1980) Insulin resistance in soleus muscle from obese Zucker rats. Biochem J 186:525–534

    PubMed  CAS  Google Scholar 

  14. Espinal J, Dohm GL, Newsholme EA (1983) Sensitivity to insulin of glycolysis and glycogen synthesis of isolated soleus muscle strips from sedentary, exercised and exercise-trained rats. Biochem J 212:453–458

    PubMed  CAS  Google Scholar 

  15. Espinal J, Challiss RAJ, Newsholme EA (1983) Effect of adenosine deaminase and an adenosine analogue on insulin sensitivity in soleus muscle of the rat. FEBS Lett 158:103–106

    Article  PubMed  CAS  Google Scholar 

  16. Fredholm BB, Sollevi A (1986) Cardiovascular effects of adenosine. Clin Physiol 6:1–21

    Article  PubMed  CAS  Google Scholar 

  17. Fuchs BD, Gorman MW, Sparks HV (1986) Adenosine release into venous plasma during free-flow exercise. Proc Soc Exp Biol Med 181:364–370

    PubMed  CAS  Google Scholar 

  18. Gliemann J, Bowes SB, Larsen TR, Rees WD (1985) The effect of catecholamines and adenosine deaminase on the glucose transport system in rat adipocytes. Biochim Biophys Acta 845:373–379

    Article  PubMed  CAS  Google Scholar 

  19. Goldberg AL, Martel SB, Kushmerick MJ (1975) In vitro preparations of the diaphragm and other skeletal muscles. Methods Enzymol 39:82–94

    Article  PubMed  CAS  Google Scholar 

  20. Green A, Newsholme EA (1979) Sensitivity of glucose transport and lipolysis of adipocytes to insulin and the effects of some metabolites. Biochem J 180:356–365

    Google Scholar 

  21. Honig CR, Frierson JL (1980) Role of adenosine in exercise vasodiation in dog gracilis muscle. Am J Physiol 238:H703–H715

    PubMed  CAS  Google Scholar 

  22. Leighton B, Lozeman FJ, Owen SA, Challiss RAJ, Pitcher J, Newsholme EA (1987) Effects of adenosine deaminase and adenosine-receptor antagonist on the sensitivity of glucose transport, glycolysis and glycogen synthesis in muscles of the rat. Int J Biochem (submitted for publication)

    Google Scholar 

  23. Londos C, Wolf J (1977) Two distinct adenosine-sensitive sites on adenylate cyclase. Proc Natl Acad Sci USA 74:5482–5486

    Article  PubMed  CAS  Google Scholar 

  24. Londos C, Wolff J, Cooper DMF (1979) Action of adenosine on adenylate cyclase. In: Bear HP, Drummond GI (eds) Physiological and regulatory functions of adenosine and adenine nucleotides. Raven, New York, pp 271–281

    Google Scholar 

  25. Lozeman FJ, Leighton B, Challiss RAJ, Owen SA, Newsholme EA (1986) The effect of adenosine deaminase on insulin sensitivity in the extensor digitorum longus muscle of the rat. Biochem Soc Trans 14:328–329

    CAS  Google Scholar 

  26. Mohrman DE, Heller LJ (1984) Effect of aminophylline on adenosine and exercise dilation of rat cremaster arterioles. Am J Physiol 246:H592–H600

    PubMed  CAS  Google Scholar 

  27. Morff RJ, Granger HJ (1983) Contribution of adenosine to arteriolar autoregulation in striated muscle. Am J Physiol 244:H567–H576

    PubMed  CAS  Google Scholar 

  28. Newby AC (1984) Adenosine and the concept of “retaliatory metabolites”. Trends Biochem Sci 9:42–44

    Article  CAS  Google Scholar 

  29. Newsholme EA (1978) Substrate cycles: their metabolic, energetic and thermic consequences in man. Biochem Soc Symp 43:183–205

    PubMed  CAS  Google Scholar 

  30. Newsholme EA, Blomstrand E, Newell J, Pitcher J (1985) Maximal activities of enzymes involved in adenosine metabolism in muscle and adipose tissue of rats under conditions of variations in insulin sensitivity. FEBS Lett 181:189–192

    Article  PubMed  CAS  Google Scholar 

  31. Phair RD, Sparks HV (1979) Adenosine content of skeletal muscle during active hyperaemia and ischaemic contraction. Am J Physiol 237:H1–H9

    PubMed  CAS  Google Scholar 

  32. Plough T, Galbo H, Richter EA (1984) Increased muscle glucose uptake during contractions: no need for insulin. Am J Physiol 247:E726–E731

    Google Scholar 

  33. Randle PJ, Morgan HE (1962) Regulation of glucose uptake by muscle. Vitam Horm 20:199–250

    Article  CAS  Google Scholar 

  34. Richter EA, Garetto LP, Goodman MN, Ruderman NB (1982) Muscle glucose metabolism following exercise in the rat: increased sensitivity to insulin. J Clin Invest 69:785–793

    Article  PubMed  CAS  Google Scholar 

  35. Richter EA, Plough T, Galbo H (1986) Increased muscle glucose uptake after exercise: no need for insulin during exercise. Diabetes 34:1041–1048

    Article  Google Scholar 

  36. Schwabe U, Schonhofer PS, Ebert R (1974) Facilitation by adenosine of the action of insulin on the accumulation of cyclic AMP, lipolysis and glucose oxidation in isolated fat cells. Eur J Biochem 46:537–545

    Article  PubMed  CAS  Google Scholar 

  37. Sibley DR, Lefkowitz RJ (1985) Molecular mechamisms of receptor desensitisation using the β-adrenergic receptorcoupled adenylate cyclase system as a model. Nature 317:124–129

    Article  PubMed  CAS  Google Scholar 

  38. Tominaga S, Curnish RR, Belardinelli L, Rubio R, Berne RM (1980) Adenosine release during early and sustained exercise of canine skeletal muscle. Am J Physiol 238:H156–H163

    PubMed  CAS  Google Scholar 

  39. Trost T, Stock K (1977) Effects of adenosine derivatives on cyclic AMP accumulation and lipolysis in rat adipocytes and on adenylate cyclase in adipocyte plasma membranes. Naunyn Schmiedebergs Arch Pharmacol 229:33–40

    Article  Google Scholar 

  40. Van Calker D, Muller M, Hamprecht B (1979) Adenosine regulates via two different types of receptors, the accumulation of cyclic AMP in cultured brain cells. J Neurochem 33:999–1005

    Article  PubMed  Google Scholar 

  41. Wardzala LJ, Jeanrenaud B (1981) Potential mechanism of insulin action on glucose transport in isolated rat diaphragm. J Biol Chem 256:7090–7093

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry, University of Oxford, UK, South Parks Road, Oxford, OX1 3QU, UK

    R. A. J. Challiss, B. Leighton, F. J. Lozeman & E. A. Newsholme

Authors
  1. R. A. J. Challiss
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  2. B. Leighton
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  3. F. J. Lozeman
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  4. E. A. Newsholme
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Editors and Affiliations

  1. Physiologisches Institut, Universität München, Pettenkoferstraße 12, 8000, München 2, Federal Republic of Germany

    Eckehart Gerlach  & Bernhard Friedrich Becker  & 

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© 1987 Springer-Verlag Berlin Heidelberg

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Challiss, R.A.J., Leighton, B., Lozeman, F.J., Newsholme, E.A. (1987). The Hormone-Modulatory Effects of Adenosine in Skeletal Muscle. In: Gerlach, E., Becker, B.F. (eds) Topics and Perspectives in Adenosine Research. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-45619-0_22

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  • DOI: https://doi.org/10.1007/978-3-642-45619-0_22

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-45621-3

  • Online ISBN: 978-3-642-45619-0

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