Advertisement

Body Fuel Metabolism

  • Philip Felig
  • Veikko Koivisto

Abstract

Fuel homeostasis in normal man involves the assimilation, storage, and utilization primarily of glucose, fat (triglyceride, free fatty acids, and glycerol), and protein (amino acids and peptides). Body fuel metabolism is of particular importance in such conditions as starvation and exercise and in disease states such as diabetes. This review will focus primarily on normal physiology, with some discussion of the abnormalities observed in diabetes.

Keywords

Lactate Cortisol Assimilation Glutamine Epinephrine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ahlborg, G., and Felig, P., 1976, Influence of glucose ingestion on fuel-hormone response during prolonged exercise,J. Appl. Physiol. 41:683.PubMedGoogle Scholar
  2. Ahlborg, G., Felig, P., Hagenfeldt, L., Hendler, R., and Wahren, J., 1974, Substrate turnover during prolonged exercise in man: Splanchnic and leg metabolism of glucose, free fatty acids and amino acids,J. Clin. Invest. 53:1080.PubMedCrossRefGoogle Scholar
  3. Aikawa, T., Matsutaka, H., Yamamoto, H., Okuda, T., Ishikawa, E., Kawano, T., and Matsumura, E., 1973, Gluconeogenesis and amino acid metabolism. II. Interorganal relations and roles of glutamine and alanine in the amino acid metabolism of fasted rats,J. Biochem. (Tokyo) 74:1003.Google Scholar
  4. Afford, F., Bloom, S., Nabarro, J., Hall, R., Besser, G., Coy, D., Kastin, A., and Schally, A. V., 1974, Glucagon control of fasting glucose in man, Lancet 2:974.CrossRefGoogle Scholar
  5. Altszuler, N., Gottlieb, B., and Hampshire, J., 1976, Interaction of somatostatin, glucagon and insulin on hepatic glucose output in the normal dog, Diabetes 25:116.PubMedCrossRefGoogle Scholar
  6. Baiasse, E. O., and Havel, R. J., 1971, Evidence for an effect of insulin on the peripheral utilization of ketone bodies in dogs,J. Clin. Invest. 50:801.CrossRefGoogle Scholar
  7. Baiasse, E. O., and Neef, M. A., 1975, Inhibition of ketogenesis by ketone bodies in fasting humans, Metabolism 24:999.CrossRefGoogle Scholar
  8. Beatty, C. H., and Bocek, R. M., 1971, Interrelation of carbohydrate and palmitate metabolism in skeletal muscle, Amer. J. Physiol. 220:1928.PubMedGoogle Scholar
  9. Berger, M., Hagg, S., and Ruderman, N. B., 1975, Glucose metabolism in perfused skeletal muscle; interaction of insulin and exercise on glucose uptake, Biochem. J. 146:231.PubMedGoogle Scholar
  10. Berger, M., Hagg, S. A., Goodman, M. N., and Ruderman, N. B., 1976, Glucose metabolism in perfused skeleton muscle. Effects of starvation, diabetes, fatty acids, acetoacetate, insulin and exercise on glucose uptake and disposition, Biochem. J. 158:191.PubMedGoogle Scholar
  11. Blackshear, P. J., Holloway, P. A. H., and Alberti, K. G. M. M., 1975, Factors regulating amino acid release from extrasplanchnic tissues in the rat. Interactions of alanine and glutamine, Biochem. J. 150:379.PubMedGoogle Scholar
  12. Bloom, S. R., and Johnston, D. I., 1972, Failure of glucagon release in infants of diabetic mothers, Br. Med. J. 4:453.PubMedCrossRefGoogle Scholar
  13. Bloom, S. R., Mortimer, C. H., Thorner, M. O., Besser, G. M., Hall, R., Gomez-Pan, A., Roy, V. M., Russel, R. C. G., Coy, D. H., Kastin, A. J., and Schally, A. V., 1974, Inhibition of gastrin and gastric acid secretion by growth hormone release-inhibiting hormone, Lancet 2:1106.PubMedCrossRefGoogle Scholar
  14. Bloom, S. R., Ralphs, D. W., Besser, G. M., Hall, R., Coy, D. H., Kastin, A. J., and Schally, A. V., 1975, Effect of somatostatin on motillin levels and gastric emptying, Gut 16:834 (abstract).PubMedCrossRefGoogle Scholar
  15. Boden, G., Sivitz, M. C., Owen, O. E., Essa-Koumar, N., and Landor, J. H., 1975, Somatostatin suppresses secretion and pancreatic exocrine secretion, Science 190:163.PubMedCrossRefGoogle Scholar
  16. Bomboy, J. D., Jr., Lewis, S. B., Lacy, W. W., Sinclair-Smith, B. C., and Liljenquist, J. E., 1977a, Transient stimulatory effect of sustained hyperglucagonemia on splanchnic glucose production in normal and diabetic man, Diabetes 26:177.CrossRefGoogle Scholar
  17. Bomboy, J. D., Jr., Lewis, S. B., Sinclair-Smith, B. C., Lacy, W. W., and Liljenquist, J. E., 1977b, Insulin-glucagon interaction in controlling splanchnic glucose production in normal man,J. Clin. Endocrinol. Metab. 44:474.CrossRefGoogle Scholar
  18. Bondy, P. K., James, D. F., and Farrar, B. W., 1949, Studies of the role of liver in human carbohydrate metabolism by the venous catheter technic. I. Normal subjects under fasting conditions and following the injection of glucose, J. Clin. Invest. 28:238.CrossRefGoogle Scholar
  19. Brazeau, P., Vale, W., Burgus, R., Ling, N., Butcher, M., Rivier, J., and Guillemin, R., 1973, Hypothalamic polypeptide that inhibits the secretion of immuno-reactive growth hormone, Science 179:77.PubMedCrossRefGoogle Scholar
  20. Buse, M. G., Biggers, J. F., Friderici, K. H., and Buse, J. F., 1972, Oxidation of branched chain amino acids by isolated hearts and diaphragms of the rat: The effect of fatty acids, glucose, and pyruvate respiration, J. Biol. Chem. 247:8085.PubMedGoogle Scholar
  21. Buse, M. G., Herlong, H. G., and Weigand, D. A., 1976, The effect of diabetes, insulin, and the redox potential on leucine metabolism by isolated rat hemidiaphragm, Endocrinology 98:1166.PubMedCrossRefGoogle Scholar
  22. Chernick, S. S., Clark, C. M., Jr., Gardiner, R. J., and Scow, R. O., 1972, Role of lipolytic and glucocorticoid hormones in the development of diabetic ketosis, Diabetes 21:946.PubMedGoogle Scholar
  23. Chiasson, J. L., Liljenquist, J. E., Finger, F. E., and Lacy, W. W., 1976, Differential sensitivity of glycogenolysis and gluconeogenesis to insulin infusions in dogs, Diabetes 25:283.PubMedCrossRefGoogle Scholar
  24. Dobbs, R., Sakurai, H., Sasaki, H., Faloona, G., Valverde, I., Baetens, D., Orci, L., and Unger, R., 1975, Glucagon: Role in the hyperglycemia of diabetes mellitus, Science 187:544.PubMedCrossRefGoogle Scholar
  25. Felig, P., 1973, The glucose-alanine cycle, Metabolism 22:179.PubMedCrossRefGoogle Scholar
  26. Felig, P., 1975, Amino acid metabolism in man, Annu. Rev. Biochem. 44:933.PubMedCrossRefGoogle Scholar
  27. Felig, P., 1976, Recent developments in body fuel metabolism, in: The Year in Metabolism 1975–76 (N. Freinkel, ed.), p. 113–136, Plenum Press, New York.CrossRefGoogle Scholar
  28. Felig, P., 1977, Body fuel metabolism and diabetes mellitus in pregnancy, Med. Clin. North Amer. 61:43.Google Scholar
  29. Felig, P., and Wahren, J., 1971a, Influence of endogenous insulin secretion on splanchnic glucose and amino acid metabolism in man, J. Clin. Invest. 50:1702.CrossRefGoogle Scholar
  30. Felig, P., and Wahren, J., 1971b, Amino acid metabolism in exercising man, J. Clin. Invest. 50:2703.CrossRefGoogle Scholar
  31. Felig, P., and Wahren, J., 1975, Fuel homeostasis in exercise (Seminars of the Beth Israel Hospital), N. Engl. J. Med. 293:1078.PubMedCrossRefGoogle Scholar
  32. Felig, P., Pozefsky, T., Marliss, E., and Canili, G. F. Jr., 1970, Alanine: Key role in gluconeogenesis, Science 167:1003.PubMedCrossRefGoogle Scholar
  33. Felig, P., Wahren, J., and Hendler, R., 1976a, Influence of physiologic hyperglu-cagonemia on basal and insulin-inhibited splanchnic glucose output in normal man,J. Clin. Invest. 58:761.CrossRefGoogle Scholar
  34. Felig, P., Wahren, J., Sherwin, R., and Hendler, R., 1976b, Insulin, glucagon and somatostatin in normal physiology and diabetes mellitus, Diabetes 25:1091.CrossRefGoogle Scholar
  35. Felig, P., Wahren, J., Sherwin, R., and Palaiologos, G., 1977, Amino acid and protein metabolism in diabetes mellitus, Arch. Intern. Med. 137:507.PubMedCrossRefGoogle Scholar
  36. Floyd, J. C., Jr., Fajans, S. S., Conn, J. W., Knopf, R. F., and Rull, J., 1966, Insulin secretion in response to protein ingestion,J. Clin. Invest. 45:1479.PubMedCrossRefGoogle Scholar
  37. Garber, A. J., Menzel, P. H., Boden, G., and Owen, O. E., 1974, Hepatic ketogenesis and gluconeogenesis in humans,J. Clin. Invest. 54:981.PubMedCrossRefGoogle Scholar
  38. Garber, A. J., Cryer, P. E., Santiago, J. V., Haymond, M. W., Pagliara, A. S., and Kipnis, D. M., 1976a, The role of adrenergic mechanism in the substrate and hormonal response to insulin-induced hypoglycemia in man, J. Clin. Invest. 58:7.CrossRefGoogle Scholar
  39. Garber, A. J., Karl, I. E., and Kipnis, D. M., 1976b, Alanine and glutamine synthesis and release from skeletal muscle. II. The precursor role of amino acids in alanine and glutamine synthesis,J. Biol. Chem. 251:836.Google Scholar
  40. Gerich, J. E., 1977, Somatostatin: Its possible role in carbohydrate homeostasis and the treatment of diabetes mellitus, Arch. Intern. Med. (in press).Google Scholar
  41. Gerich, J. E., Lorenzi, M., Schneider, V., Karam, J. H., Rivier, J., Guillemin, R., and Forsham, P. H., 1974, Effects of somatostatin on plasma glucose and glucagon levels in human diabetes mellitus, N. Engl. J. Med. 291:544.PubMedCrossRefGoogle Scholar
  42. Gerich, J. E., Lorenzi, M., Bier, D. M., Tsalikian, E., Schneider, V., Karam, J. H., and Forsham, P. H., 1976, Effects of physiologic levels of glucagon and growth hormone on human carbohydrate and lipid metabolism, J. Clin. Invest. 57:875.PubMedCrossRefGoogle Scholar
  43. Goldberg, A. L., and Odessey, R., 1972, Oxidation of amino acids by diaphragms from fed and fasted rats, Amer. J. Physiol. 223:1384.PubMedGoogle Scholar
  44. Goldstein, L., and Newsholme, E. A., 1976, The formation of alanine from amino acids in diaphragm muscle of the rat, Biochem. J. 154:555.PubMedGoogle Scholar
  45. Gomez-Pan, A., Reed, J. D., Albinus, M., Shaw, B., Hall, R., Besser, G. M., Coy, D. H., Kastin, A. J., and Schally, A. V., 1975, Direct inhibition of gastric acid and pepsin secretion by growth hormone release-inhibiting hormone in cats, Lancet 1:888.PubMedCrossRefGoogle Scholar
  46. Hultman, E., and Nillsson, L. H., 1971, Liver glycogen in man. Effect of different diets and muscular exercise, Adv. Exp. Med. Biol. 11:143.Google Scholar
  47. Kalhan, S. C., Savin, S. M., and Adam, P. A. J., 1977, Attenuated glucose production rate in newborn infants of insulin-dependent diabetic mothers, N. Engl. J. Med. 296:375.PubMedCrossRefGoogle Scholar
  48. Kawamori, R., and Vranic, M., 1977, Mechanism of exercise-induced hypoglycemia in depancreatized dogs maintained on long-acting insulin, J. Clin. Invest. 59:331.PubMedCrossRefGoogle Scholar
  49. Koerker, D. L., Ruch, W., Chideckel, E., Palmer, J., Goodner, C. J., Ensinck, J., and Gale, C. C., 1974, Somatostatin: Hypothalamic inhibitor of the endocrine pancreas, Science 184:482.PubMedCrossRefGoogle Scholar
  50. Koivisto, V. A., and Felig, P., 1977, Effects of exercise on insulin release from injection sites in diabetic man, Diabetes 26 (Suppl. 1):357.Google Scholar
  51. Liljenquist, J. E., Bomboy, J. D., Lewis, S. B., Sinclair-Smith, B. C., Felts, P. W., Lacy, W. W., Crofford, O. B., and Liddle, G. W., 1974, Effects of glucagon on lipolysis and ketogenesis in normal and diabetic man,J. Clin. Invest. 53:190.PubMedCrossRefGoogle Scholar
  52. Lindsey, A., Santeusanio, F., Braaten, J., Faloona, G. F., and Unger, R. H., 1974, Pancreatic alpha cell function in trauma,J. Amer. Med. Assoc. 227:757.CrossRefGoogle Scholar
  53. Madison, L. L., 1969, Role of insulin in the hepatic handling of glucose, Arch. Intern. Med. 123:284.PubMedCrossRefGoogle Scholar
  54. Mallette, L. E., Exton, J. H., and Park, C. R., 1969, Control of gluconeogenesis from amino acids in the perfused rat liver,J. Biol. Chem. 244:5713.Google Scholar
  55. Mann, F. S., and MaGath, T. B., 1922, Studies on the physiology of the liver. II. The effect of the removal of the liver on the blood sugar level, Arch. Intern. Med. 30:73.CrossRefGoogle Scholar
  56. Marliss, E. B., Aoki, T. T., Toews, C. J., Felig, P., Connon, J. J., Kyner, J., Huckabee, W. E., and Canili, G. F., Jr., 1972, Amino acid metabolism in lactic acidosis, Amer. J. Med. 52:474.PubMedCrossRefGoogle Scholar
  57. Odessey, R., and Goldberg, A. L., 1972, Oxidation of leucine by rat skeletal muscle, Amer. J. Physiol. 223:1376.PubMedGoogle Scholar
  58. Odessey, R., Khairallah, E. A., and Goldberg, A. L., 1974, Origin and possible significance of alanine production by skeletal muscle,J. Biol. Chem. 249:7623.PubMedGoogle Scholar
  59. Palaiologos, G., and Felig, P., 1976, Effects of ketone-bodies on amino acid metabolism in isolated rat diaphragm, Biochem. J. 154:709.PubMedGoogle Scholar
  60. Patton, G., Ipp, E., Schusdziarra, V., Dobbs, R., Orci, L., Vale, W., and Unger, R., 1977, Studies of pancreatic somatostatin secretion, Clin. Res. 25:523A.Google Scholar
  61. Pederson, J., Boljsen-Moller, B., and Poulsen, H., 1954, Blood sugar in newborn infants of diabetic mothers, Acta Endocrinol. (Copenhagen) 15:33.Google Scholar
  62. Persson, B., Gentz, J., and Kellum, M., 1973, Metabolic observations in infants of strictly controlled diabetic mothers; plasma levels of glucose, FFA, glycerol and D-beta-hydroxybutyrate during the first two hours after birth, Acta Paediatr. Scand. 62:465.PubMedCrossRefGoogle Scholar
  63. Pozefsky, T., Felig, P., Tobin, J., Soeldner, J. S., and Cahili, G. F., Jr., 1969, Amino acid balance across tissues of the forearm in postabsorptive man: Effects of insulin at two dose levels,J. Clin. Invest. 48:2273.PubMedCrossRefGoogle Scholar
  64. Randle, P. J., Garland, P. B., Hales, C. N., and Newsholme, E. A., 1963, The glucose fatty acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus, Lancet 1:785.PubMedCrossRefGoogle Scholar
  65. Rennie, M. J., Winder, W. W., and Holloszy, J. O., 1976, A sparing effect of increased plasma fatty acids on muscle and liver glycogen content in the exercising rat, Biochem. J. 156:647.PubMedGoogle Scholar
  66. Rocha, D. M., Santeusanio, F., Faloona, G. R., and Unger, R. H., 1973, Abnormal pancreatic alpha cell function in bacterial infections, N. Engl. J. Med. 288:700.PubMedCrossRefGoogle Scholar
  67. Ruderman, N. B., and Berger, M., 1974, The formation of glutamine and alanine in skeletal muscle, J. Biol. Chem. 249:5500.PubMedGoogle Scholar
  68. Sacca, L., Perez, G., Carteni, G., and Frengo, F., 1977, Evaluation of the role of the sympathetic nervous system in the glucoregulatory response to insulin-induced hypoglycemia in the rat, Endocrinology (in press).Google Scholar
  69. Sanders, C. A., Levinson, G. E., Abelman, W. H., and Freinkel, N., 1964, Effect of exercise on peripheral utilization of glucose in man, N. Engl. J. Med. 271:220.PubMedCrossRefGoogle Scholar
  70. Schade, D. S., and Eaton, R. P., 1976, Modulation of fatty acid metabolism by glucagon in man. IV. Effects of physiologic hormone infusion in normal man, Diabetes 25:978.PubMedCrossRefGoogle Scholar
  71. Sherwin, R., Joshi, P., Hendler, R., Felig, P., and Conn, H. O., 1974, Hyperglucagonemia in Laennec’s cirrhosis. The role of portal-systemic shunting, N. Engl. J. Med. 290:239.PubMedCrossRefGoogle Scholar
  72. Sherwin, R. S., Basti, C., Finkelstein, F. O., Fisher, M., Black, H., Hendler, R., and Felig, P., 1976a, Influence of uremia and hemodialysis on the turnover and metabolic effects of glucagon,J. Clin. Invest. 57:722.CrossRefGoogle Scholar
  73. Sherwin, R. S., Fisher, M., Hendler, R., and Felig, P., 1976b, Hyperglucagonemia and blood glucose regulation in normal, obese and diabetic subjects, N. Engl. J. Med. 294:455.CrossRefGoogle Scholar
  74. Sherwin, R. S., Hendler, R., and Felig, P., 1976c, Effect of diabetes mellitus and insulin on the turnover and metabolic response to ketones in man, Diabetes 25:776.CrossRefGoogle Scholar
  75. Sherwin, R., Rosenzweig, J., Soman, V., Hendler, R., and Felig, P., 1976d, Effect of insulin and diabetes on protein and branched chain amino acid utilization, Diabetes 25 (Suppl. 1):332.Google Scholar
  76. Sherwin, R. S., Hendler, R., DeFronzo, R. A., Wahren, J., and Felig, P., 1977, Glucose homeostatis during prolonged suppression of glucagon and insulin secretion by somatostatin, Proc. Natl. Acad. Sci. U.S.A. 74:348.PubMedCrossRefGoogle Scholar
  77. Shikama, H., and Ui, M., 1975, Adrenergic receptor and epinephrine-induced hyperglycemia and glucose tolerance, Amer. J. Physiol. 229:962.Google Scholar
  78. Siler, T. M., Vandenberg, G., and Yen, S. S. C., 1973, Inhibition of growth hormone release in humans by somatostatin,J. Clin Endocrinol. Metab. 37:632.PubMedCrossRefGoogle Scholar
  79. Snell, K., 1976, Alanine release by rat hemidiaphragm muscle in vitro, Biochem. Soc. Trans. 4:287.Google Scholar
  80. Snell, K., and Duff, D. A., 1977, The release of alanine by rat diaphragm muscle in vitro, Biochem. J. 162:399.Google Scholar
  81. Stephens, J. M., Sulway, M. J., and Watkins, P. J., 1971, Relationship of blood acetoacetate and 3-beta-hydroxybutyrate in diabetes, Diabetes 20:485.PubMedGoogle Scholar
  82. Stern, L., Ramos, A., and Leduc, J., 1968, Urinary catecholamine excretion in infants of diabetic mothers, Pediatrics 42:598.PubMedGoogle Scholar
  83. Sugden, M. C., Sharpies, S. C., and Randle, P., 1976, Carcass glycogen as a potential source of glucose during short-term starvation, Biochem. J. 160:817.PubMedGoogle Scholar
  84. Unger, R. H., Ohneda, A., Aquilar-Parada, E., and Eisentraut, A. M., 1969, The role of aminogenic glucagon secretion in blood glucose homeostatis, J. Clin. Invest. 48:810.PubMedCrossRefGoogle Scholar
  85. Vranic, M., Kawamori, R., Pek, S., Kovacevic, N., and Wrenshall, G. A., 1976, The essentiality of insulin and the role of glucagon in regulating glucose utilization and production during strenous exercise in dogs, J. Clin. Invest. 57:245.PubMedCrossRefGoogle Scholar
  86. Wahren, J., and Felig, P., 1976, Influence of somatostatin on carbohydrate disposal and absorption in diabetes mellitus, Lancet 2:1213.PubMedCrossRefGoogle Scholar
  87. Wahren, J., Felig, P., Havel, R. J., Jorfeldt, L., Pernow, B., and Saltin, B., 1973, Amino acid metabolism in McArdle’s syndrome, N. Engl. J. Med. 288:774.PubMedCrossRefGoogle Scholar
  88. Wahren, J., Hagenfeldt, L., and Felig, P., 1975, Splanchnic and leg exchange of glucose, amino acids, and free fatty acids during exercise in diabetes mellitus, J. Clin. Invest. 55:1303.PubMedCrossRefGoogle Scholar
  89. Wahren, J., Felig, P., and Hangefeldt, L., 1976, Effect of protein ingestion on splanchnic and leg metabolism in normal man and in patients with diabetes mellitus,J. Clin. Invest. 57:987.PubMedCrossRefGoogle Scholar
  90. Wahren, J., Efendic, S., Luft, R., Hagenfeldt, L., Bjorkman, O., and Felig, P., 1977, Influence of somatostatin on splanchnic glucose metabolism in postab-sorptive and 60-hour fasted humans,J. Clin. Invest. 59:299.PubMedCrossRefGoogle Scholar
  91. Wildenhof, K. E., 1976, Blood ketone body disappearance rate in diabetics and normals after rapid infusion of DL-3-hydroxybutyrate. Studies before and after diabetic treatment, Acta Med. Scand. 200:79.CrossRefGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1978

Authors and Affiliations

  • Philip Felig
    • 1
    • 2
  • Veikko Koivisto
    • 3
  1. 1.Department of Internal MedicineYale University School of MedicineNew HavenUSA
  2. 2.Section of EndocrinologyYale University School of MedicineNew HavenUSA
  3. 3.Section of Endocrinology, Department of Internal MedicineYale University School of MedicineNew HavenUSA

Personalised recommendations