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Research Article

Vol. 1 No. 2 (1995)

Effect of Physical Training on the Activity of the Low Km Phosphodiesterase in Heart Ventricular and Skeletal Muscle Tissues of Normal and Diabetic Rats

DOI
https://doi.org/10.26443/mjm.v1i2.430
Submitted
October 31, 2020
Published
2020-12-01

Abstract

This study assessed the effect of physical training on the low Michaelis constant cyclic AMP phosphodiesterase (low Km PDE) activity in heart ventricular tissue and three different skeletal muscle tissues of normal and diabetic rats. Rats were rendered diabetic with streptozotocin (45 mg/kg i.v.) and either kept sedentary (SD, n=16) or submitted to a progressive 10-week treadmill running program (TD, n=17). Two groups of nondiabetic rats served as trained (TC, n=17) and sedentary controls (SC, n=15). The activity of NAD-linked isocitrate dehydrogenase was significantly increased (p < 0.001) in the gastrocnemius muscle of trained animals, confirming that they were adequately trained. Plasma glucose levels were elevated in SD rats (18.8 ± 1.7 mmol/l) compared to those in SC rats (7.7 ± 0.2 mmol/l ; mean ± standard error of the mean [SEM], p < 0.001). These levels were partially normalized following training (12.7 ± 1.7 pmol/l; p < 0.01 vs. SD rats). Plasma insulin levels were significantly reduced in TC rats (223 ± 16 pmol/l) compared with those in SC rats (306 ± 13 pmol/l; p < 0.01). Similarly, the levels in SC rats were significantly different when compared with SD rats (155 ± 15 pmol/l; p < 0.01). In TD rats, plasma insulin levels (156 ± 14 pmol/l) were similar to those of SD rats. This suggests that mild diabetes mellitus in the rat can be improved by endurance training and that improved glycemic control may be mediated by an increase in insulin sensitivity. The low Km PDE activity in the membranes prepared from the four different muscle tissues was not modified by diabetes. Similarly, physical training in normal and diabetic rats did not induce any significant changes in the low Km PDE activity in any of the tissues tested. This suggests that improvements in myocardial contractile function and in glucose homeostasis, as seen in diabetic rats submitted to endurance training, are not associated with changes in PDE.

References

  1. Kannel WB, Hjortland M, and Castelli WP. Role of diabetes in congestive heart failure: the Framingham study. American Journal of Cardiology 34: 29-34; 1974.
  2. Nadeau A, Rousseau-Migneron S, and Tancrède G. Exercise training improves early survival rate in diabetic rats submitted to acute coronary artery ligation. Diabetes Research 9: 37-40; 1988.
  3. Braunwald E, Sonnenblick EH, and Ross J Jr. Mechanisms of cardiac contraction and relaxation. In: Braunwald E (ed.). Heart Disease, A Textbook of Cardiovascular Medicine, 3rd ed. Philadelphia, PA: Saunders, 383-425, 1988.
  4. Feldman MD, Copelas S, Gwathmey JK, et al. Deficient production of cyclic AMP: pharmacologic evidence of an important cause of contractile dysfunction in patients with end-stage heart failure. Circulation 75: 331-339; 1988.
  5. Morgan JP, Erny RE, Allen PD, Grossman W, Gwathmey JK. Abnormal intracellular calcium handling, a major cause of systolic and diastolic dysfunction in ventricular myocardium from patients with heart failure. Circulation 81(suppl. III): 21-32; 1990.
  6. Butcher RW, and Sutherland EW. Adenosine 3',5'-phosphate in biological materials. Journal of Biological Chemical 37: 1244-1250; 1962.
  7. Plourde G, Martin M, Rousseau-Migneron S, Nadeau A. Effect of physical training on ventricular ß- adrenergic receptor adenylate cyclase system of diabetic rats. Metabolism 40: 362-367; 1991.
  8. Thompson WJ, Appleman MM. Characterization of cyclic nucleotide phosphodiesterases of rat tissues. Journal of Biological Chemistry 246: 3145-3150; 1971.
  9. Paulson DJ, Kopp SJ, Peace DG, Tow JP. Myocardial adaptation to endurance exercise training in diabetic rats. American Journal of Physiology 252: R1073-R1081; 1987.
  10. Tancrède G, Rousseau-Migneron S, Nadeau A. Beneficial effects of physical training in rats with a mild streptozotocin-induced diabetes mellitus. Diabetes 31: 406-409; 1982.
  11. Reaven GM, Chang F. Effect of exercise-training on the metabolic manifestations of streptozotocin- induced diabetes in rat. Diabetologia 21: 415-417; 1981.
  12. Tan MH, Bonen A, Garner JB, Belcastro AN. Physical training in diabetic rats: effect of glucose tolerance and serum lipids. Journal of Applied Physiology 52: 1514-1518; 1982.
  13. Dall'Aglio E, Chang F, Chang H, Wright D, Reaven GM. Effect of exercise training and sucrose feeding on insulin-stimulated glucose uptake in rats with streptozotocin-induced-insulin-deficient diabetes. Diabetes 32: 165-168; 1983.
  14. Hartley LH, Mason JW, Hogan RP, et al. Multiple hormonal responses to graded exercise in relation to physical training. Journal of Applied Physiology 33: 602-606; 1972.
  15. Galbo H, Holst JJ, Christensen NJ. Glucagon and plasma catecholamines responses to graded and prolonged exercise in man. Journal of Applied Physiology 38: 70-76; 1975.
  16. Ellis S. The metabolic effects of epinephrine and related amines. Pharmacological Reviews 8: 485-562; 1956.
  17. Himms-Hagen J. Sympathetic regulation of metabolism. Pharmacological Reviews 19: 368-461; 1967.
  18. Gerich JE, Langlois M, Noacco C, Schneider V, Forsham PH. Adrenergic modulation of pancreatic glucagon secretion in man. Journal of Clinical Investigation 53: 1441-1446; 1974.
  19. Porte D Jr, Williams RH. Inhibition of insulin release by norepinephrine in man. Science 152: 1248-1250; 1966.
  20. Plourde G, Rousseau-Migneron S, Nadeau A. Physical training increases the number of ß-adrenergic receptors and adenylate cyclase activity in high-oxidative skeletal muscle of diabetic rats. Metabolism 41: 1331-1335; 1992.
  21. Saltin B, Gollnick PD. Skeletal muscle adaptability: significance for metabolism and performance. In: Handbook of Physiology. Skeletal Muscle. Bethesda, MD: American Physiological Society, 555-631, 1983.
  22. Armstrong RB, Phelps RO. Muscle fiber composition of the rat hindlimb. American Journal of Anatomy 171: 259-272; 1984.
  23. Plourde G, Rousseau-Migneron S, Nadeau A. Effect of endurance training on ß-adrenergic system in three different skeletal muscles. Journal of Applied Physiology 74: 1641-1646; 1993.
  24. Buckenmeyer PJ, Goldfarb AH, Partilla JS, Pineyro MA, Dax EM. Endurance training, not acute exercise, differentially alters ß-receptors and cyclase in skeletal fiber types. American Journal of Physiology 258: E71-E77; 1990.
  25. Tancrède G, Rousseau-Migneron S, Nadeau A. Long-term changes in the diabetic state induced by different doses of streptozotocin in rats. British Journal Experimental Pathology 64: 117-123; 1983.
  26. Pattengale PK, Holloszy JD. Augmentation of skeletal muscle myoglobin by a program of treadmill running. American Journal of Physiology 213: 783-785; 1967.
  27. Stiles GL, Strasser RH, Kilpatrick BF, Taylor SR, Lefkowitz RJ. Endogenous proteinases modulate the function of the ß-adrenergic receptor-adenylate cyclase system. Biochimica et Biophysica Acta 802: 390-398; 1984.
  28. Lowry OH, Rosenbrough NJ, Farr AL, Randall R. Protein measurement with Folin phenol reagent. Journal of Biological Chemistry 193: 265-275; 1951.
  29. Loten EG, Sneyd JGT. An effect of insulin on adipose-tissue adenosine 3',5'-cyclic monophosphate phosphodiesterase. Biochemical Journal 120: 187-193; 1970.
  30. Lineweaver H, Burk DJ. The determination of enzymes dissociation constants. Journal of the American Chemical Society 56: 658-666; 1934.
  31. Weber HW, Appleman MM. Insulin-dependent and insulin-independent low Km phosphodiesterase from adipose tissue. Journal of Biological Chemistry 257: 5339-5341; 1982.
  32. Richterich R, Dauwalder H. Zur bestimmung der Plasmaglucose-konzentration mit der Hexokinase- glucose-6-phosphat-dehydrogenase-methode. Schweizerische Medizinische Wochenschrift. Journal Suisse de Medecine 101: 615-18; 1971.
  33. Desbuquois B, Aurbach GD. Use of polyethylene glycol to separate free and antibody-bound peptide hormones in radioimmunoassays. Journal of Clinical Endocrinology 33: 732-738; 1971.
  34. Vaughan H, Newsholme EA. The effects of Ca2+ and ADP on the activity of NAD-linked isocitrate dehydrogenase of muscle. FEBS Letters 5: 124-126; 1969.
  35. Booth FW, Thomason DB. Molecular and cellular adaptation of muscle in response to exercise: perspectives of various models. Physiological Reviews 71: 541-585; 1991.
  36. Holloszy JO, Oscai LB, Don IJ, Molé PA. Mitochondrial citric acid cycle and related enzymes: adaptative response to exercise. Biochemical and Biophysical Research Communications 40: 1368-1373; 1970.
  37. Benzi G. Endurance training and enzymatic activities in skeletal muscle. In: diPrampero PE, Poortmans JR (eds.). Physiological Chemistry of Exercise and Training. New York, NY: Karger, Basel, 165-174, 1981.
  38. Kimball SR, Flaim KE, Peavy DE, et al. Protein metabolism. In: Rifkin H, Porte D Jr (eds.). Ellenberg and Rifkin's Diabetes mellitus: Theory and Practice. New York, NY: Elsevier Science, 41-50, 1990.
  39. Dohm GL, Pennington SN, Barakat H. Effect of exercise training on adenyl cyclase and phosphodiesterase in skeletal muscle, heart, and liver. Biochemical Medicine 16: 138-142; 1976.
  40. Scheuer J, Tipton CM. Cardiovascular adaptations to physical training. Annual Review of Physiology 39: 221-251; 1977.
  41. Tipton CM. Training and bradycardia in rats. American Journal of Physiology 209: 1089-1094; 1965.
  42. Plourde G, Rousseau-Migneron S, and Nadeau A. ß-adrenoceptor adenylate cyclase system adaptation to physical training in rat ventricular tissue. Journal of Applied Physiology 70: 1633-1638; 1991.
  43. Solomon SS. Effect of insulin and lipolytic hormones on cyclic AMP phosphodiesterase activity in normal and diabetic rat adipose tissue. Endocrinology 96: 1366-1373; 1975.
  44. Solomon SS, Palazzolo M, Mcpherson J, Smoake AL. Effects of experimental diabetes and insulin on cyclic AMP phosphodiesterase and its protein activator in rat adipose tissue. Diabetes 30: 372-376; 1981.
  45. Solomon SS, Silberberg M, and Palazzolo MR. Measurement of protein activator levels in experimental diabetic rat adipose tissue. Biochemical and Biophysical Research Communications 86: 379-386; 1979.
  46. Schmitz W, Eschenhagen T, Mende, Müller FU, Neumann J, Scholz H. Phosphodiesterase inhibition and positive inotropy in failing human myocardium. In: Hasenfuss G, Holubarsh CH, Just H, Alpert NR (eds.). Cellular and molecular alterations in the failing human heart. Steinkopff Verlag Darmstadt, 65-71, 1992.

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