Summary
During the initial phase of physical exercise muscle glycogen is the primary source of fuel for contracting muscle in normal man. When exercise continues beyond the first 5–10 min blood glucose and free fatty acids (FFA) become increasingly important substrates. Glucose utilization may account for 25–35% of the total substrate supply during mild to moderately heavy exercise. The augmented glucose utilization by working muscle is balanced by a rise in hepatic glucose production. The latter is achieved primarily by hepatic glycogenolysis during brief work, but during prolonged exercise gluconeogenesis may account for as much as 40–50% of the hepatic glucose output. Muscle uptake of FFA is determined primarily by its availability to the working muscle, and it may account for 30–60% of the total fuel supply. Ketone bodies are not utilized by working muscle in normal man. In patients with diabetes mellitus the metabolic effects of physical exercise are to a large extent determined by the time interval between insulin administration and the onset of exercise. Thus, in insulin treated patients with mild hyperglycaemia and no or minimal ketonaemia the utilization of glycogen, blood glucose and FFA by working muscle is similar to that of healthy subjects, and exercise is accompanied by a fall in blood glucose levels. In contrast, patients with more marked hyperglycaemia and hyperketonaemia may respond to exercise with a further rise in both blood glucose and ketone body levels, reflecting augmented rates of hepatic gluconeogenesis as well as ketogenesis. The repletion of muscle and liver glycogen, which takes place for 24–48 h after exercise, requires — besides carbohydrate feeding — a minimum concentration of insulin. Glycogen resynthesis probably accounts for a major part of the empirically well established beneficial effect of physical exercise in diabetic patients. The above considerations underscore the importance of adequate insulin administration in connection with exercise in diabetic patients.
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References
Tulloch, J.A.: Diabetes mellitus in the tropics, p. 2. London: Livingstone 1962
von Noorden, C.: Die Zuckerkrankheit und ihre Behandlung, p. 498. Berlin: Hirschwald 1917
Brasch, W.: Beobachtungen aus fiebernden Diabetiker. Dtsch. Arch. Klin. Med.97, 508–528 (1909)
Frerichs, F.T.: Über den Diabetes, p. 260–290. Berlin: Hirschwald 1884
Lawrence, R.D.: The effect of exercise on insulin action in diabetes. Br. Med. J.1926 I, 648–650
Hetzel, K.L., Long, C.N. H.: The metabolism of the diabetic individual during and after muscular exercise. Proc. R. Soc. Lond. [Biol.]99, 279–306 (1926)
Bürger, M., Kramer, H.: Über die durch Muskelarbeit hervorgerufene Steigerung der Insulinwirkung auf den Blutzuckergehalt beim Normalen und Gestörten Kohlehydratstoffwechsel und ihre praktische und theoretische Bedeutung. Klin. Wochenschr.7, 745–750 (1928)
Barringer, T.B., Jr.: The effect of exercise upon the carbohydrate tolerance in diabetes. Am. J. Med. Sci.151, 181–184 (1916)
Mering, A. von, Minkowski, O.: Diabetes mellitus nach Pankreasexstirpation. Naunyn-Schmiedebergs Arch. Pharmacol.26, 371–387 (1890)
Hildes, J.A., Sherlock, S., Walshe, V.: Liver and muscle glycogen in normal subjects, in diabetes mellitus and acute hepatitis. I. Under basal conditions. Clin. Sci.7, 287–295 (1949)
Roch-Norlund, A.E., Bergström, J., Castenfors, H., Hultman, E.: Muscle glycogen in patients with diabetes mellitus. Glycogen content before treatment and the effect of insulin. Acta Med. Scand.187, 445–453 (1970)
Roch-Norlund, A.E.: Muscle glycogen synthetase in patients with diabetes mellitus. Basal values, effect of glycogen depletion by exercise, and effect of treatment. Scand. J. Clin. Lab. Invest.29, 237–242 (1972)
Hultman, E.: Studies on muscle metabolism of glycogen and active phosphate in man with special reference to exercise and diet. Scand. J. Clin. Lab. Invest.19 (Suppl. 94), 1–63 (1967)
Saltin, B., Karlsson, J.: Muscle glycogen utilization during work of different intensities. In: B. Pernow, B. Saltin. (Ed.): Muscle Metabolism during Exercise, p. 289–299. New York: Plenum Press 1971
Hermansen, L., Hultman, E., Saltin, B.: Muscle glycogen during prolonged severe exercise. Acta Physiol. Scand.71, 129–139 (1967)
Ahlborg, B., Bergström, J., Ekelund, L.-G., Guarnieri, G., Harris, R.C., Hultman, E., Nordesjö, L.-O.: Muscle metabolism during isometric exercise performed at constant force. J. Appl. Physiol.33, 224–228 (1972)
Maehlum, S., Høstmark, A.T., Hermansen, L.: Synthesis of muscle glycogen during recovery after prolonged severe exercise in diabetic and non-diabetic subjects. Scand. J. Clin. Lab. Invest.37, 309–316 (1977)
Maehlum, S., Høstmark, A.T., Hermansen, L.: Synthesis of muscle glycogen during recovery after prolonged severe exercise in diabetic subjects. Effect of insulin deprivation. Scand. J. Clin. Lab. Invest.38 (in press) (1978)
Chauveau, M.A., Kaufmann, M.: Expériences pour la détermination du coefficient de l'activité nutritive et respiratoire des muscles en repos et en travail. C. R. Acad. Sci. [D] (Paris)104, 1126–1132 (1887)
Jorfeldt, L., Wahren, J.: Human forearm muscle metabolism during exercise. V. Quantitative aspects of glucose uptake and lactate production during prolonged exercise. Scand. J. Clin. Lab. Invest.26, 73–81 (1970)
Wahren, J., Felig, P., Ahlborg, G., Jorfeldt, L.: Glucose metabolism during leg exercise in man. J. Clin. Invest.50, 2715–2725 (1971)
Andres, R., Cader, G., Zierler, K.L.: The quantitatively minor role of carbohydrate in oxidative metabolism by skeletal muscle in intact man in the basal state. Measurements of oxygen and glucose uptake and carbon dioxide and lactate production in the forearm. J. Clin. Invest.35, 671–682 (1956)
Ahlborg, G., Felig, P., Hagenfeldt, L., Hendler, R., Wahren, J.: Substrate turnover during prolonged exercise in man: Splanchnic and leg metabolism of glucose, free fatty acids and amino acids. J. Clin. Invest.53, 1080–1090 (1974)
Pirnay, F., Lacroix, M., Mosora, F., Luyckx, A., Lefebvre, P.: Glucose oxidation during prolonged exercise evaluated with naturally labeled (13C) glucose. J. Appl. Physiol.43, 258–261 (1977)
Sanders, C.A., Levinson, G.E., Abelmann, W.H., Freinkel, N.: Effect of exercise on the peripheral utilization of glucose in man. N. Engl. J. Med.271, 220–225 (1964)
Wahren, J., Hagenfeldt, L., Felig, P.: Splanchnic and leg exchange of glucose amino acids, and free fatty acids during exercise in diabetes mellitus. J. Clin. Invest.55, 1303–1314 (1975)
Lyngsøe, J., Clausen, J. P., Trap-Jensen, J., Sestoft, L., Schaffalatizky de Muckadell, O., Holst, J. J., Nielsen, S. L., Rehfeld, J. F.: Exchange of metabolites in the leg of exercising juvenile diabetics. Clin. Sci. Mol. Med.54 (in press) (1978)
Vranic, M., Kawamori, R., Wrenshall, G.A.: Mechanism of exercise-induced hypoglycemia in depancreatized insulintreated dogs. Diabetes23 (Suppl. 1), 353 (1974)
Böttger, I., Schlein, E.M., Faloona, G.R., Knochel, J.P., Unger, R.H.: The effect of exercise on glucagon secretion. J. Clin. Endocrinol. Metab.35, 117–125 (1972)
Franckson, J.R. M., Vanroux, R., Leclercq, R., Brunengraber, H., Ooms, H.A.: Labelled insulin catabolism and pancreatic responsiveness during long-term exercise in man. Horm. Metab. Res.3, 366–373 (1971)
Berger, M., Hagg, S., Ruderman, N.B.: Glucose metabolism in perfused skeletal muscle. Interaction of insulin and exercise on glucose uptake. Biochem. J.146, 231–238 (1975)
Levin, S.A., Gordon, B., Derick, C.L.: Some changes in the chemical constituents of the blood following a marathon race. J.A.M.A.82, 1778–1779 (1924)
Nilsson, L. Hison, Fürst, P., Hultman, E.: Carbohydrate metabolism of the liver in normal man under varying dietary conditions. Scand. J. Clin. Lab. Invest.32, 331–337 (1973)
Owen, O.E., Felig, P., Morgan, A.P., Wahren, J., Cahill, F., Jr.: Liver and kidney metabolism during prolonged starvation. J. Clin. Invest.48, 574–583 (1969)
Felig, P., Wahren, J.: Influence of endogenous insulin secretion on splanchnic glucose and amino acid metabolism in man. J. Clin. Invest.50, 1702–1711 (1971)
Marble, A., Smith, R.M.: Exercise in diabetes mellitus. Arch. Intern. Med.58, 577–588 (1936)
Errebo-Knudsen, E.O.: Diabetes mellitus and exercise. A physiopathologic study of muscular work in patients with diabetes mellitus, p. 78. Copenhagen: G.E.C. Gad 1948
Berger, M., Berchtold, P., Cüppers, H.J., Drost, H., Kley, H.K., Müller, W.A., Wiegelmann, W., Zimmermann-Telschow, H., Gries, F.A., Krüskemper, H.L., Zimmermann, H.: Metabolic and hormonal effects of muscular exercise in juvenile type diabetics. Diabetologia13, 355–365 (1977)
Sestoft, L., Trap-Jensen, J., Lyngsøe, J., Clausen, J.P., Holst, J.J., Nielsen, S.L., Rehfeld, J.F., Schaffalitzky de Muckadell, O.: Regulation of gluconeogenesis and ketogenesis during rest and exercise in diabetic subjects and normal man. Clin. Sci. Mol. Med.53, 411–418 (1977)
Wahren, J., Felig, P., Cerasi, E., Luft, R.: Splanchnic and peripheral glucose and amino acid metabolism in diabetes mellitus. J. Clin. Invest.51, 1870–1878 (1972)
Bondy, P.K., Bloom, W.L., Whitner, V.S., Farrar, B.W.: Studies of the role of the liver in human carbohydrate metabolism by the venous catheter technic. II. Patients with diabetic ketosis, before and after the administration of insulin.J. Clin. Invest.28, 1126–1133 (1949)
Hansen, Aa. P.: Normalization of growth hormone hyper-response to exercise in juvenile diabetics after normalization of blood sugar. J. Clin. Invest.50, 1806–1811 (1971)
Hartley, L.H., Mason, J.W., Hogan, R.P.: Multiple hormonal responses to graded exercise in relation to physical training. J. Appl. Physiol.33, 602–606 (1972)
Edwards, A.V.: The sensitivity of the hepatic glycogenolytic mechanism to stimulation of the splanchnic nerves. J. Physiol.220, 315–334 (1972)
Björkman, O., Felig, P., Wahren, J.: Importance of glucagon for the splanchnic glucose production during exercise. Svenska Läkarsällskapets Handlingar86, 227 (1977)
Christensen, E.H., Hansen, O.: Untersuchungen über die Verbrennungsvorgänge bei langdauernder, schwerer Muskelarbeit. Skand. Arch. Physiol.81, 152–159 (1939)
Dole, V.P.: A relation between non-esterified fatty acids in plasma and the metabolism of glucose. J. Clin. Invest.35, 150–154 (1956)
Rabinowitz, D., Zierler, K.L.: Role of free fatty acids in forearm metabolism in man quantitated by use of insulin. J. Clin. Invest.41, 2191–2197 (1962)
Hagenfeldt, L., Wahren, J.: Human forearm muscle metabolism during exercise. II. Uptake, release and oxidation of individual FFA and glycerol. Scand. J. Clin. Lab. Invest.21, 263–276 (1968)
Havel, R.J., Pernow, B., Jones, N.: Uptake and release of free fatty acids and other metabolites in the legs of exercising man. J. Appl. Physiol.23, 90–99 (1967)
Hagenfeldt, L., Wahren, J., Pernow, B., Rät, L.: Uptake of individual free fatty acids by skeletal muscle and liver in man. J. Clin. Invest.51, 2324–2330 (1972)
Hagenfeldt, L., Wahren, J.: Metabolism of free fatty acids and ketone bodies in skeletal muscle. In: B. Pernow, B. Saltin (eds.): Muscle metabolism during exercise, p. 153–163. New York: Plenum Press 1971
Hagenfeldt, L., Wahren, J.: Human forearm muscle metabolism during exercise. III. Uptake, release and oxidation ofβ-hydroxybutyrate and observations on theβ-hydroxybutyrate/ acetoacetate ratio. Scand. J. Clin. Lab. Invest.21, 314–320 (1968)
Rennie, M.J., Park, D.M., Sulaiman, W.R.: Uptake and release of hormones and metabolites by tissues of exercising leg in man. Am. J. Physiol.231, 967–973 (1976)
Åkerblom, H.: Blood acetone bodies of juvenile diabetics after exercise. Ann. Paediatr. Fenn.11 (Suppl. 25), 1–48 (1965)
Löffler, F., Matschinsky, F., Wieland, O.: Über den Mechanismus der gesteigerten Ketonkörperbildung. II. Redox-Status des DPN der isolierten Rattenleber bei Durchströmung mit Fettsäuren. Biochem. Z.342, 76–84 (1965)
Björntorp, P., Berchtold, P., Grimby, G., Lindholm, B., Sänne, H., Tibblin, G., Wilhelmsen, L.: Effects of physical training on glucose tolerance, plasma insulin and lipids and on body composition in men after myocardial infarction. Acta Med. Scand.192, 439–443 (1972)
Maehlum, S., Pruett, E.E.R.: Muscular exercise and metabolism in male juvenile diabetics. II. Glucose tolerance after exercise. Scand. J. Clin. Lab. Invest.32, 149–153 (1973)
Engerbretson, D.L.: The effects of exercise upon diabetic control. J. Assoc. Phys. Ment. Rehab.19, 74–78 (1965)
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Wahren, J., Felig, P. & Hagenfeldt, L. Physical exercise and fuel homeostasis in diabetes mellitus. Diabetologia 14, 213–222 (1978). https://doi.org/10.1007/BF01219419
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DOI: https://doi.org/10.1007/BF01219419