Skip to main content
SpringerLink
Log in
Book cover

GLUCAGON: Its Role in Physiology and Clinical Medicine pp 563–581Cite as

Role of the Insulin/Glucagon Ratio in the Changes of Hepatic Metabolism During Development of the Rat

  • Conference paper

Abstract

The insulin/glucagon ratio was measured during the embryologic development of the rat and its changes were correlated with the variation in the diet and in hepatic metabolism. During late fetal life, the high carbohydrate diet and the high insulin/glucagon ratio are appropriate for an organism whose metabolism is set at a maximally anabolic mode: growth, protein synthesis, liver glycogen storage. After birth and during suckling, rapid growth can coexist with active gluconeogenesis and ketogenesis in the liver and with a low insulin/glucagon ratio, since the mother’s milk is a high fat diet. The weaning period is characterized by a replacement of this high fat by a high carbohydrate diet. Suppression of gluconeogenesis and ketogenesis and appearance of an active lipogenesis in the liver occur, with a rise in insulin/glucagon ratio. These data suggest that glucagon plays a more important role during early life than during adult life.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Augenfeld, J. and Fritz, I. B. (1970): Carnitine palmitoyl transferase activity and fatty acid oxidation by livers from fetal and neonatal rats. Canadian J. Biochem. 48, 288–294.

    Article  CAS  Google Scholar 

  2. Bailey, E. and Lockwood, E. A. (1973): Some aspects of fatty acid oxidation and ketone body formation and utilization during development of the rat. Enzyme 15, 239–253.

    PubMed  CAS  Google Scholar 

  3. Ballard, F. J. (1970): Gluconeogenesis and the regulation of blood glucose in the neonate. In: Diabetes, R. R. Rodriguez and J. Vallance-Owen, eds. Excerpta Medica, Amsterdam, p. 592–600.

    Google Scholar 

  4. Ballard, F. J. and Hanson, R. W. (1967): Changes in lipid synthesis in rat liver during development. Biochem. J. 102, 952–958.

    PubMed  CAS  Google Scholar 

  5. Ballard, F. J., Hopgood, M. F., Reshef, L. and Hanson, R. W. (1975): Changes in protein synthesis and degradation involved in enzyme accumulation in differentiating liver. In: The Biochemistry of Gene Expression in Higher Organisms, J. K. Pollak and J. W. Lee, eds. D. Reidel, Boston, p. 274.

    Google Scholar 

  6. Ballard, F. J. and Oliver, I. T. (1963): Glycogen metabolism in embryonic chick and neonatal rat liver. Biochim. Biophys. Acta 71, 578–588.

    Article  PubMed  CAS  Google Scholar 

  7. Bataille, D., Jarousse, C., Vauclin, N., Gestach, C. and Rosselin, G. (1977): Effect of vasoactive intestinal peptide (VIP) and gastric inhibitory peptide ( GIP) on insulin and glucagon release by perifused newborn rat pancreas. This volume, p. 255–270.

    Google Scholar 

  8. Blazquez, E., Rubalcava, B., Montesano, R., Orci, L. and Unger, R. H. (1976): Development of insulin and glucagon binding and the adenylate -cyclase response in liver membranes of the prenatal, postnatal and adult rat: evidence of glucagon “resistance”. Endocrinology 98, 1014–1023.

    Article  PubMed  CAS  Google Scholar 

  9. Blazquez, E., Sugase, T., Blazquez, M. and Foa, P. P. (1972): The ontogeny of metabolic regulation in the rat, with special reference to the development of insular function. Acta Diabetol. Latina 9 suppl. 1, 13–35.

    Google Scholar 

  10. Blazquez, E., Sugase, T., Blazquez, M. and Foa, P. P. (1974): Neonatal changes in the concentration of rat liver cyclic AMP and of serum glucose, free fatty acids, insulin, pancreatic and total glucagon in man and in the rat. J. Lab. Clin. Med. 83, 957–967.

    PubMed  CAS  Google Scholar 

  11. Böttger, I., Dobbs, R., Faloona, G. R. and Unger, R. H. (1973): The effects of triglyceride absorption upon glucagon, insulin and gut glucagon-like immunoreactivity. J. Clin. Invest. 52, 2532–2541.

    Article  PubMed  Google Scholar 

  12. Brown, J. C. (1974): Gastric inhibitory polypeptide (GIP). In: Endocrinology 1973, S. Taylor, ed. W. Heinemann, London, p. 276–284.

    Google Scholar 

  13. Coufalik, A. and Monder, C. (1976): Spontaneous development of gluconeogenesis in fetal rat livers during incubation in organ culture. Proc. Soc. Exptl. Biol. Med. 152, 603–605.

    CAS  Google Scholar 

  14. Eisen, H. J., Glinsmann, W. H. and Sherline, P. (1973): Effect of insulin on glycogen synthesis in fetal rat liver in organ culture. Endocrinology 92, 584–588.

    Article  PubMed  CAS  Google Scholar 

  15. Eisen, H. J., Goldfine, I. D. and Glinsmann, W. H. (1973): Regulation of hepatic glycogen synthesis during fetal development: role of hydrocortisone, insulin and insulin receptors. Proc. Natl. Acad. Sci. ( USA ) 70, 3454–3457.

    Article  CAS  Google Scholar 

  16. Eisenstein, A. B., Strack, I. and Steiner, A. (1974): Increased hepatic gluconeogenesis without a rise of glucagon secretion in rats fed a high fat diet. Diabetes 23, 869–875.

    PubMed  CAS  Google Scholar 

  17. Exton, J. H. and Park, C. R. (1972): Interaction of insulin and glucagon in the control of liver metabolism. In: Handbook of Physiology, Endocrine Pancreas. D. F. Steiner and N. Freinkel, Eds. Amer. Physiol. Soc. Washington, pp. 437–455.

    Google Scholar 

  18. Ferre, P., Pegorier, J. P. and Girard, J. R. (1977): The effects of inhibition of gluconeogenesis in suckling newborn rats. Biochem. J. 162, 209–212.

    PubMed  CAS  Google Scholar 

  19. Ferre, P., Pegorier, J. P., Marliss, E. B. and Girard, J. R. (1977): Influence of exogenous fat of gluconeogenic substrates on glucose homeostasis in the newborn rat. Am. J. Physiol, (accepted for publication).

    Google Scholar 

  20. Geelen, M. J. H. and Gibson, D. M. (1975): Lipogenesis in maintenance cultures of rat hepatocytes. FEBS Letters 58, 334–339.

    Article  PubMed  CAS  Google Scholar 

  21. Ghisalberti, A. V. (1976): Enzyme induction in perinatal rat liver. Ph.D. Thesis, University of Western Australia.

    Google Scholar 

  22. Gilbert, M. (1977): Origin and metabolic fate of plasma glycerol in the rat and rabbit fetus. Pediat. Res. 11, 95–99.

    Article  PubMed  CAS  Google Scholar 

  23. Girard, J. R. (1975): Metabolic fuels of the fetus. Israel J. Med. Sci. 11, 591–600.

    PubMed  CAS  Google Scholar 

  24. Girard, J. and Bal, D. (1970): Effets du glucagon-zinc sur la glycémie et la teneur en glycogéne du foie foetal du rat en fin de gestation. C. R. Acad. Sci. ( Paris ) 271, 777–779.

    Google Scholar 

  25. Girard, J. R., Cuendet, G. S., Marliss, E. B., Kervran, A., Rieutort, M. and Assan, R. (1973): Fuels, hormones and liver metabolism at term and during the early postnatal period in the rat. J. Clin. Invest. 52, 3190–3200.

    Article  PubMed  CAS  Google Scholar 

  26. Girard, J. R., Ferre, P., Gilbert, M., Kervran, A., Assan, R. and Marliss, E. B. (1977): Fetal metabolic response to maternal fasting in the rat. Am. J. Physiol., 232, 456–463.

    PubMed  CAS  Google Scholar 

  27. Girard, J. R., Ferre, P. and Pegorier, J. P. (1976): Glucose homeostasis in the fasted newborn rats: role of lipids and gluconeogenic substrates. Diabetologia 12, 393 (abst.).

    Article  Google Scholar 

  28. Girard, J. R., Guillet, I., Marty, J. and Marliss, E. B. (1975): Plasma amino acid levels and development of hepatic gluconeogenesis in the newborn rat. Am. J. Physiol. 229, 466–473.

    Google Scholar 

  29. Girard, J. R., Guillet, I., Marty, J., Assan, R. and Marliss, E. B. (1976): Effects of exogenous hormones and glucose on plasma levels and hepatic metabolism of amino acids in the fetus and in the newborn rat. Diabetologia 12, 327–337.

    Article  PubMed  CAS  Google Scholar 

  30. Girard, J. R., Kervran, A. and Assan, R. (1975): Functional maturation of the A cell in the rat. In: Early Diabetes in Early Life, R. A. Camerini- Davalos and H. S. Cole, Eds. Academic Press, New York, pp. 57–71.

    Google Scholar 

  31. Girard, J. R., Kervran, A., Soufflet, E. and Assan, R. (1974): Factors affecting the secretion of insulin and glucagon by the rat fetus. Diabetes 23, 310–317.

    PubMed  CAS  Google Scholar 

  32. Greengard, O. and Dewey, H. K. (1970): The premature deposition or lysis of glycogen in livers of fetal rats injected with hydrocortisone or glucagon. Develop. Biol. 21, 452–461.

    Google Scholar 

  33. Griglio, S. and Malewiak, M. I. (1975): Triglyceride storage, ketonemia, and fat diets. Nutr. Metab. 19, 131–144.

    Article  PubMed  CAS  Google Scholar 

  34. Hahn, P. and Kirby, L. (1973): Immediate and late effects of premature weaning and of feeding a high fat or high carbohydrate diet to weanling rats. J. Nutr. 103, 690–696.

    PubMed  CAS  Google Scholar 

  35. Hahn, P. and Kirby, L. T. (1974): The effects of catecholamines, glucagon and diet on enzyme activities in brown fat and liver of the rat. Canadian J. Biochem. 52, 739–743.

    Google Scholar 

  36. Hanson, R. W., Reshef, L. and Ballard, F. J. (1975): Hormonal regulation of hepatic P-enolpyruvate carboxykinase (GTP) during development. Fed. Proc. 34, 166–171.

    PubMed  CAS  Google Scholar 

  37. Heimberg, M., Weinstein, I. and Kohout, M. (1969): The effects of glucagon, dibutyryl cyclic adenosine 3′5′ monophosphate and concentration of free fatty acid on hepatic lipid metabolism. J. Biol. Chem. 244, 5131–5139.

    Google Scholar 

  38. Hunter, D. J. S. (1969): Changes in blood glucose and liver carbohydrate after intrauterine injection of glucagon into foetal rats. J. Endocrinol. 45, 367–374.

    Article  PubMed  CAS  Google Scholar 

  39. Jansen, G. R., Hutchison, C. F. and Zanetti, M. E. (1966): Studies on lipogenesis in vivo. Effect of dietary fat or starvation on conversion of 14C-glucose into fat and turnover of newly synthetized fat. Biochem. J. 99, 323–332.

    Google Scholar 

  40. Jeejeebhoy, K. N., Anderson, G. H., Nakhooda, A. F., Greenberg, G. R., Sanderson, I. and Marliss, E. B. (1976): Metabolic studies in total parenteral nutrition with lipid in man: comparison with glucose. J. Clin. Invest. 57, 125–136.

    Article  CAS  Google Scholar 

  41. Jost, A. and Picon, L. (1970): Hormonal control of fetal development and metabolism. Adv. Metab. Dis. 4, 123–184.

    Google Scholar 

  42. Kervran, A., Gilbert, M., Girard, J. R., Assan, R. and Jost, A. (1976): Effect of environmental temperature on glucose-induced insulin response in the newborn rat. Diabetes 25, 1026–1030.

    Article  PubMed  CAS  Google Scholar 

  43. Lee, L. P. K. and Fritz, I. B. (1971): Hepatic ketogenesis during development. Canadian J. Biochem. 49, 599–605.

    Google Scholar 

  44. Lockwood, E. A., Bailey, E. and Taylor, C. B. (1970): Factors involved in changes in hepatic lipogenesis during development of the rat. Biochem. J. 118, 155–162.

    PubMed  CAS  Google Scholar 

  45. Luckey, T. D., Mende, T. J. and Pleasants, J. (1954): The physical and chemical characterization of rat’s milk. J. Nutr. 54, 345–359.

    PubMed  CAS  Google Scholar 

  46. Mackrell, D. J. and Sokal, J. E. (1969): Antagonism between the effects of insulin and glucagon on the isolated liver. Diabetes 18, 724–732.

    PubMed  CAS  Google Scholar 

  47. Manns, J. G. and Brockman, R. P. (1969): The role of insulin in the synthesis of fetal glycogen. Canadian J. Physiol. Pharmacol. 47, 917–921.

    Google Scholar 

  48. McGarry, J. D., Robles-Valdes, C. and Foster, D. W. (1975): The role of carnitine in hepatic ketogenesis. Proc. Natl. Acad. Sci. ( USA ) 72, 4385–4388.

    Article  CAS  Google Scholar 

  49. McGarry, J. D., Wright, P. H. and Foster, D. W. (1975): Hormonal control of ketogenesis. Rapid activation of hepatic ketogenic capacity in fed rats by anti-insulin serum and glucagon. J. Clin. Invest. 55, 1202–1209.

    Google Scholar 

  50. Menahan, L. A. and Wieland, O. (1969): Interactions of glucagon and insulin on the metabolism of perfused livers from fasted rats. Europ. J. Biochem. 9, 55–62.

    Article  PubMed  CAS  Google Scholar 

  51. Orci, L., Malaisse-Lagae, F., Ravazzola, M., Rouiller, D., Renold, A. E., Perrelet, A. and Unger, R. H. (1975): A morphological basis for intercellular communication between A and B cells in the endocrine pancreas. J. Clin. Invest. 56, 1066–1070.

    Google Scholar 

  52. Parrilla, R., Goodman, M. N. and Toews, C. J. (1974): Effect of glucagon: insulin ratios on hepatic metabolism. Diabetes 23, 725–731.

    PubMed  CAS  Google Scholar 

  53. Pearce, P. H., Buirchell, B. J., Weaver, P. K. and Oliver, I. T. (1974): The development of phosphopyruvate carboxylase and gluconeogenesis in neo-natal rats. Biol. Neonate 24, 320–329.

    Google Scholar 

  54. Philippidis, H. and Ballard, F. J. (1969): The development of gluconeo-genesis in rat liver. Experiments in vivo. Biochem. J. 113, 651–657.

    PubMed  CAS  Google Scholar 

  55. Philippidis, H., Hanson, R. W., Reshef, L., Hopgood, M. F. and Ballard, F. J. (1972): The initial synthesis of proteins during development. Phosphoenol pyruvate carboxylase in rat liver at birth. Biochem. J. 126, 1127–1134.

    Google Scholar 

  56. Picon, L. (1967): Effect of insulin on growth and biochemical composition of the rat fetus. Endocrinology 81, 1419–1421.

    Article  PubMed  CAS  Google Scholar 

  57. Plas C. and Nunez, J. (1975): Glycogenolytic response to glucagon of cultured fetal hepatocytes. Refractoriness following prior exposure to glucagon. J. Biol. Chem. 250, 5304–5311.

    Google Scholar 

  58. Plas, C. and Nunez, J. (1976): Role of Cortisol on the glycogenolytic effect of glucagon and on the glycogenic response to insulin in fetal hepatocyte culture. J. Biol. Chem. 251, 1431–1437.

    PubMed  CAS  Google Scholar 

  59. Portha, B., Leprovost, E., Picon, L. and Rosselin, G. (1977): Postmaturity in the rat: phosphorylase, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities in the fetal liver. Horm. Metab. Res. (submitted for publication).

    Google Scholar 

  60. Portha, B., Rosselin, G. and Picon, L. (1976): Postmaturity in the rat: impairment of insulin, glucagon and glycogen stores. Diabetologia 12, 429–436.

    Article  PubMed  CAS  Google Scholar 

  61. Rabain, F. and Picon, L. (1974): Effect of insulin on the maternofetal transfer of glucose in the rat. Horm. Metab. Res. 6, 376–380.

    Google Scholar 

  62. Robles-Valdes, C., McGarry, J. D. and Foster, D. W. (1976): Maternal- fetal carnitine relationships and neonatal ketosis in the rat. J. Biol. Chem. 251, 6007–6012.

    PubMed  CAS  Google Scholar 

  63. Schwartz, A. L. and Rail, T. W. (1973): Hormonal regulation of glycogen metabolism in neonatal rat liver. Biochem. J. 134, 985–993.

    PubMed  CAS  Google Scholar 

  64. Snell, K. and Walker, D. G. (1973): Gluconeogenesis in the newborn rat: the substrates and their quantitative significance. Enzyme 15, 40–81.

    PubMed  CAS  Google Scholar 

  65. Taylor, C. B., Bailey, E. and Bartley, W. (1967): Changes in hepatic lipogenesis during development of the rat. Biochem. J. 105, 717–722.

    Google Scholar 

  66. Topping, D. L. and Mayes, P. A. (1972): The immediate effects of insulin and fructose on the metabolism of the perfused liver. Changes in lipoprotein secretion, fatty acid oxidation and esterification, lipogenesis and carbohy-drate metabolism. Biochem. J. 126, 295–311.

    CAS  Google Scholar 

  67. Unger, R. H. (1974): Alpha- and beta-cell interrelationships in health and disease. Metabolism 23, 581–593.

    Article  PubMed  CAS  Google Scholar 

  68. Unger, R. H. and Orci, L. (1976): Physiology and pathophysiology of glucagon. Physiol. Rev. 56, 778–826.

    Google Scholar 

  69. Vernon, R. G., Eaton, S. W. and Walker, D. G. (1968): Carbohydrate formation from various precursors in neonatal rat liver. Biochem. J. 110, 725–731.

    PubMed  CAS  Google Scholar 

  70. Vernon, R. G. and Walker, D. G. (1968): Changes in activity of some enzymes involved in glucose utilization and formation in developing rat liver. Biochem. J. 106, 321–329.

    Google Scholar 

  71. Vernon, R. G. and Walker, D. G. (1968): Adaptative behaviour of some enzymes involved in glucose utilization and formation in rat liver during the weaning period. Biochem. J. 106, 331–338.

    PubMed  CAS  Google Scholar 

  72. Vinicor, F., Higdon, G., Clark, J. F. and Clark, C. M, Jr. (1976): Development of glucagon sensitivity in neonatal rat liver. J. Clin. Invest. 58, 571–578.

    Article  PubMed  CAS  Google Scholar 

  73. Warshaw, J. B. (1974): Fatty acid oxidation during development. In: Parenteral Nutrition in Infancy and Childhood, H. H. Bode and J. B. Warshaw, eds. Plenum, New York, p. 88–97.

    Google Scholar 

  74. White, P. K. and Miller, S. A. (1976): Utilization of dietary amino acids for energy production in neonatal rat liver. Pediat. Res. 10, 158–164.

    Article  PubMed  CAS  Google Scholar 

  75. Yeh, Y. Y. and Zee, P. (1976): Insulin, a possible regulator of ketosis in newborn and suckling rats. Pediat. Res. 10, 192–197.

    Article  PubMed  CAS  Google Scholar 

  76. Yeung, D. and Oliver, I. T. (1967): Gluconeogenesis from amino acids in neonatal rat liver. Biochem. J. 103, 744–748.

    PubMed  CAS  Google Scholar 

  77. Yeung, D. and Oliver, I. T. (1968): Factors affecting the premature induction of phosphopyruvate carboxylase in neonatal rat liver. Biochem. J. 108, 325–331.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratoire de Physiologie du Developpement, College de France, Paris, France

    J. R. Girard, P. Ferre, A. Kervran, J. P. Pegorier & R. Assan

Authors
  1. J. R. Girard
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. Ferre
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Kervran
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. P. Pegorier
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R. Assan
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Physiology, Wayne State University School of Medicine, 48201, Detroit, Michigan, USA

    Piero P. Foà

  2. Department of Medicine, All-India Institute of Medical Sciences, 110016, New Delhi, India

    Jasbir S. Bajaj

  3. Department of Research, Sinai Hospital of Detroit, 48235, Detroit, Michigan, USA

    Naomi L. Foà

Rights and permissions

Reprints and permissions

Copyright information

© 1977 Springer-Verlag New York Inc.

About this paper

Cite this paper

Girard, J.R., Ferre, P., Kervran, A., Pegorier, J.P., Assan, R. (1977). Role of the Insulin/Glucagon Ratio in the Changes of Hepatic Metabolism During Development of the Rat. In: Foà, P.P., Bajaj, J.S., Foà, N.L. (eds) GLUCAGON: Its Role in Physiology and Clinical Medicine. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-6366-1_36

Download citation

  • DOI: https://doi.org/10.1007/978-1-4612-6366-1_36

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4612-6368-5

  • Online ISBN: 978-1-4612-6366-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation