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Role of Adenosine in Regulation of Carbohydrate Metabolism in Contracting Muscle

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 441))

Abstract

Adenosine production from AMP in the sarcoplasm and interstitial space of muscle is markedly enhanced during contractions. The produced adenosine may act as a ‘local hormone’ by binding to various types of adenosine receptors present in the membrane of adjacent cells, including skeletal muscle, vascular smooth muscle and neurons. Thus, interstitial adenosine may significantly contribute to regulation of muscle carbohydrate metabolism, both by adjusting metabolism and local blood flow to the energy needs imposed by a given degree of contratile activity on the muscle cell. The studies presented here demonstrate that endogenous adenosine via A1-adenosine receptors is able to directly stimulate insulin-mediated glucose transport in oxidative muscle cells during contractions. In addition, adenosine may further contribute to stimulation of muscle glucose uptake during contractions by increasing blood flow and thereby targetting glucose and insulin delivery to active muscle fibres. Furthermore, our findings demonstrate that adenosine via A1-and A2-receptors may inhibit glycogen breakdown in oxidative muscle tissue which during contractions is simultaneously exposed to insulin and β-adrenergic stimulation. It is concluded that adenosine importantly contributes to regulation of carbohydrate metabolism in oxidative muscle fibers during contractions.

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References

  1. Achike, F. I., and H. J. Ballard. Influence of stimulation parameters on the release of adenosine, lactate and CO2 from contracting dog gracilis muscle. J. Physiol. 463: 107–121, 1993.

    PubMed  CAS  Google Scholar 

  2. Ahmed, A. H., K. A. Jacobson, J. Kim, and L. A. Heppel. Presence of both A1 and A2a adenosine receptors in human cells and their interaction. Biochem. Biophys. Res. Comm. 208: 871–878, 1995.

    Article  PubMed  CAS  Google Scholar 

  3. Baron, A.D. Hemodynamic actions of insulin. Am. J. Physiol. 267: E187–E202, 1991.

    Google Scholar 

  4. Bjorkman, O., P. Miles, D. Wasserman, L. Lickley, and M. Vranic. Regulation of glucose turnover during exercise in pancreatectomized, totally insulin-deficient dogs: effect of β-adrenergic blockade. J. Clin. Invest. 81: 1759–1767, 1988.

    Article  PubMed  CAS  Google Scholar 

  5. Bonen, A., M.H. Tan, and W.M. Watson-Wright. Insulin binding and glucose uptake differences in rodent skeletal muscle. Diabetes 30: 702–704, 1981.

    Article  PubMed  CAS  Google Scholar 

  6. Bruns, R. F., J. H. Fergus, E. W. Badger, J. A. Bristol, L. A. Santay, J. D. Hartman, S. J. Hays, and C. C. Huang. Binding of the A1-selective adenosine antagonist 8-cyclopentyl-1,3-dipropylxantine to rat brain membranes. Naunyn-Schmiedeberg’s Arch. Pharmacol. 335: 59–63, 1987.

    Article  CAS  Google Scholar 

  7. Bruns, R.F. Adenosine receptors: role and pharmacology, Ann. N. Y. Acad. Sci. 603: 211–226, 1990.

    Article  CAS  Google Scholar 

  8. Challis, R. A. J., S. J. Richards, and L. Budohoski. Characterization of the adenosine receptor modulating insulin action in rat skeletal muscle. Eur. J. Pharmacol. 226: 121–128, 1992.

    Article  Google Scholar 

  9. Collis, M.G., and S.M.O. Hourani. Adenosine receptor subtypes. Trends Physiol. Sci. 14: 360–366, 1993.

    Article  CAS  Google Scholar 

  10. Costa, F., and I. Biaggioni. Role of adenosine in the sympathetic activation produced by isometric exercise in humans. J. Clin. Invest. 93: 1654–1660, 1994.

    Article  PubMed  CAS  Google Scholar 

  11. Cunha, R.A., and A.M. Sebastiao. Adenosine and adenine nucleotides are independently released from both nerve terminals and the muscle fibres upon electrical stimulation of the innervated skeletal muscle of the frog. Pflügers Archiv 424: 503–510, 1993.

    Article  PubMed  CAS  Google Scholar 

  12. DeFronzo, R.A., E. Ferrannini, Y. Sato, and P. Felig. Synergistic interaction between exerciseand insulin on peripheral glucose uptake. J. Clin. Invest. 68: 1468–1474, 1981.

    Article  PubMed  CAS  Google Scholar 

  13. Fredholm, B. B. On the mechanism of action of theophylline and caffeine. Acta Med. Scand. 217: 149–153, 1985.

    Article  PubMed  CAS  Google Scholar 

  14. Fredholm, B. B., and T. V. Dunwiddie. How does adenosine inhibit transmitter release? Trends Physiol. Sci. 9: 130–134, 1988.

    CAS  Google Scholar 

  15. Fushiki, T., J.A. Wells, E.B. Tapscott, and G.L. Dohm. Change in glucose transporters in muscle in response to exercise. Am. J. Physiol. 256: E580–E587, 1989.

    PubMed  CAS  Google Scholar 

  16. Goodyear, L.J., P.A. King, M.F. Hirshman, C.M. Thompson, E.D. Horton, and E.S. Horton. Contractile activity increases plasma membrane glucose transporters in absence of insulin. Am. J. Physiol. 258: E667–E672, 1990.

    PubMed  CAS  Google Scholar 

  17. Hellsten, Y., and U. Frandsen. Adenosine formation in contracting primary rat skeletal muscle cells and endothelial cells in culture. J. Physiol. 504: 695–704, 1997.

    Article  PubMed  CAS  Google Scholar 

  18. Hespel, P., L. Vergauwen, K. Vandenberghe, and E. A. Richter. Important role of insulin and flow in stimulating glucose uptake in contracting skeletal muscle. Diabetes 44: 210–215, 1995.

    Article  PubMed  CAS  Google Scholar 

  19. Holloszy, J.O. and H.T. Narahara. Studies on tissue permeability. X. Changes in permeablity to 3-O-methylglucose associated with contractions of isolated frog muscle. J. Biol. Chem. 240: 3493–3500, 1965.

    PubMed  CAS  Google Scholar 

  20. Honnor, R. C., G. S. Dhillon, and C. Londos. cAMP-dependent protein kinase and lipolysis in rat adipocytes. J. Biol. Chem. 260: 15130–15138, 1985.

    PubMed  CAS  Google Scholar 

  21. Iwamoto, T., S. Umemura, Y. Toya, T. Uchibori, K. Kogi, N. Takagi, and M. Ishii. Identification of adenosine A2 receptor-cAMP system in human aortic endothelial cells. Biochem. Biophys. Res. Comm. 199: 905–910, 1994.

    Article  PubMed  CAS  Google Scholar 

  22. James, D. E., A. B. Jenkins, and E. W. Kraegen. Heterogeneity of insulin action in individual muscles in vivo. Euglycemic clamp studies in rats. Am. J. Physiol. 248: E567–E574, 1985.

    PubMed  CAS  Google Scholar 

  23. Joost, H.G., and H.J. Steinfelder. Effects of theophylline on insulin receptors and insulin action in the adipocyte. Mol. Cell. Biochem. 57: 177–183, 1983.

    Article  PubMed  CAS  Google Scholar 

  24. Kaufman, M.P. Invited editorial on “Femoral arterial injection of adenosine in humans elevates MSNA via central but not peripheral mechanisms”. J. Appl. Physiol. 83: 1043–1044, 1997.

    PubMed  CAS  Google Scholar 

  25. Law, W.R., M.P. McLane, and R.M. Raymond. Adenosine is required for myocardial insulin responsiveness in vivo. Diabetes 37: 842–845, 1988.

    Article  PubMed  CAS  Google Scholar 

  26. Law, W. R., and R. M. Raymond. Adenosine potentiates insulin-stimulated myocardial glucose uptake in vivo. Am. J. Physiol. 254: H970–H975, 1988.

    PubMed  CAS  Google Scholar 

  27. Leighton, B., F.J. Lozeman, I.G. Vlachonikolis, R.J.A. Challis, J.A. Pitcher, and E.A. Newsholme. Effects of adenosine deaminase on the sensitivity of glucose transport, glycolysis and glycogen synthesis to insulin in muscles of he rat. Int. J. Biochem. 20: 23–27, 1988.

    Article  PubMed  CAS  Google Scholar 

  28. MacLean, D.A., G. Rådegran, Y. Hellsten, and J. Bangsbo. Measurement of muscle interstitial adenosine levels by microdialysis during incremental dynamic exercise in humans. J. Physiol. 491P: 126P, 1996.

    Google Scholar 

  29. MacLean, D. A., B. Saltin, G. Rådegren, and L. Sinoway. Femoral arterial injection of adenosine in humans elevates MSNA via central but not peripheral mechanisms. J. Appl. Physiol. 83: 1045–1053, 1997.

    PubMed  CAS  Google Scholar 

  30. May, J.M. Inhibition of hexose transport by adenosine derivatives in human erythrocytes. J. Cell. Physiol. 135: 332–338, 1988.

    Article  PubMed  CAS  Google Scholar 

  31. Möser, G.H., J. Schrader, and A. Deussen. Turnover of adenosine in human and dog blood. Am. J. Physiol. 156: C799–C806, 1989.

    Google Scholar 

  32. Nesher, R., I.E. Karl, and D.M. Kipnis. Dissociation of effects of insulin and contraction on glucose transport in rat epitrochlearis muscle. Am. J. Physiol. 249: C226–C232, 1985.

    PubMed  CAS  Google Scholar 

  33. Olah, M.E., and G.L. Stiles. Adenosine receptors. Annu. Rev. Physiol. 54: 211–225, 1992.

    Article  PubMed  CAS  Google Scholar 

  34. Olsson, R. A., and J. D. Pearson. Cardiovascular purinoceptors. Physiol. Rev. 70: 761–845, 1990.

    PubMed  CAS  Google Scholar 

  35. Ploug, T., H. Galbo, and E.A. Richter. Increased muscle glucose uptake during contractions: no need for insulin. Am. J. Physiol. 247: E726–E731, 1984.

    PubMed  CAS  Google Scholar 

  36. Raguso, C. A., A. R. Coggan, L. S. Sidossis, A. Gastaldelli, and R. R. Wolfe. Effect of theophylline on substrate metabolism during exercise. Metabolism 45: 1153–1160, 1996.

    Article  PubMed  CAS  Google Scholar 

  37. Richter, E.A., T. Ploug, and H. Galbo. Increased muscle glucose uptake after exercise. No need for insulin during exercise. Diabetes 34: 1041–1048, 1985.

    Article  PubMed  CAS  Google Scholar 

  38. Richter, E. A., N. B. Ruderman, M. Gavras, E. R. Belur, and H. Galbo. Muscle glycogenolysis during exercise. Dual control by epinephrine and contractions. Am. J. Physiol. 242: E25–32, 1982.

    PubMed  CAS  Google Scholar 

  39. Schwartz, L. M., and J. E. McKenzie. Adenosine and active hyperemia in soleus and gracilis muscle of cats. Am. J. Physiol. 259: H1295–H1304, 1990.

    PubMed  CAS  Google Scholar 

  40. Seale, T. W., K. A. Abla, M. T. Shamim, J. M. Carney, and J. W. Daly. 3,7-dimethyl-1-propargylxantine: a potent and selective in vivo antagonist of adenosine analogs. Life Sci. 43: 1671–1684, 1988.

    Article  PubMed  CAS  Google Scholar 

  41. Steinfelder, H.J., and S. Pethö-Schramm. Methylxanthines inhibit glucose transport in rat adipocytes by two independent mechanisms. Biochem. Pharmacol. 40: 1154–1157, 1983.

    Article  Google Scholar 

  42. Stiles, G.L. Adenosine receptors. J. Biol. Chem. 267: 6451–6454, 1992.

    PubMed  CAS  Google Scholar 

  43. Taylor, W.M., and M.L. Halperin. Stimulation of glucose transport in rat adipocytes by insulin, adenosine, nicotinic acid and hydrogen peroxide. Biochem. J. 178: 381–389, 1979.

    PubMed  CAS  Google Scholar 

  44. Vergauwen, L., P. Hespel, and E. A. Richter. Adenosine receptors mediate synergistic stimulation of glucose uptake and transport by insulin and by contractions in rat skeletal muscle. J. Clin. Invest. 93: 974–981, 1994.

    Article  PubMed  CAS  Google Scholar 

  45. Vergauwen, L., E.A. Richter, and P. Hespel. Adenosine exerts a glycogen-sparing action in contracting rat skeletal muscle. Am. J. Physiol. 272: E762–E768, 1997.

    PubMed  CAS  Google Scholar 

  46. Vranic, M., R. Kawamori, S. Pek, N. Kovacevic, and G.A. Wrenshall. The essentiality of insulin and the role of glucagon in regulating glucose utilization and production during strenuous exercise in dogs. J. Clin. Invest. 57: 245–255, 1976.

    Article  PubMed  CAS  Google Scholar 

  47. Vranic, M., and G.A. Wrenshall. Exercise, insulin, and glucose turnover in dogs. Endocrinology 85: 165–171, 1969.

    Article  PubMed  CAS  Google Scholar 

  48. Wallberg-Henriksson, H., and J.O. Holloszy. Contractile activity increases glucose uptake by muscle in severely diabetic rats. J. Appl. Physiol. 57: 1049–1054, 1984.

    Google Scholar 

  49. Wasserman, D.H., J.L. Bupp, J.L. Johnson, D. Bracy, and L.D. Brooks. Glucoregulation during rest and exercise in depancreatectomized dogs: role of the acute presence of insulin. Am. J. Physiol. 262: E574–E582, 1992.

    PubMed  CAS  Google Scholar 

  50. Wasserman, D.H., R.J. Geer, D.E. Rice, D. Bracy, P.J. Flakoll, L.L. Brown, J.O. Brown, and N.N. Abumrad. Interaction of exercise and insulin in humans. Am. J. Physiol. 260: E37–E45, 1991.

    PubMed  CAS  Google Scholar 

  51. Wasserman, D.H., H.L.A. Lickley, and M. Vranic. Important role of glucagon during exercise in diabetic dogs. J. Appl. Physiol. 59: 1272–1281, 1985.

    PubMed  CAS  Google Scholar 

  52. Wasserman, D.H., T. Mohr, P. Kelly, L.D. Brooks, and D. Bracy. Impact of insulin deficiency on glucose fluxes and muscle glucose metabolism during exercise. Diabetes 41: 1229–1238, 1992.

    Article  PubMed  CAS  Google Scholar 

  53. Wieringa, T., K. Van Dam, M.P. Bos, J.P.M. Van Putten, and H.M.J. Krans. The effects of 1-methyl-3-isobutylxanthine on insulin-sensitive 2-deoxyglucoe transport. Biochim. Biophys. Acta 803: 123–128, 1984.

    Article  CAS  Google Scholar 

  54. Yamatani, K., Z. Qing Shi, A. Giaccia, R. Gupta, S. Fisher, and H.L.A. Lickley. Role of FFA-glucose cycle in glucoregulation during exercise in total absence of insulin. Am. J. Physiol. 262: E646–E653, 1992.

    Google Scholar 

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Hespel, P., Richter, E.A. (1998). Role of Adenosine in Regulation of Carbohydrate Metabolism in Contracting Muscle. In: Richter, E.A., Kiens, B., Galbo, H., Saltin, B. (eds) Skeletal Muscle Metabolism in Exercise and Diabetes. Advances in Experimental Medicine and Biology, vol 441. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1928-1_9

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  • DOI: https://doi.org/10.1007/978-1-4899-1928-1_9

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4899-1930-4

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