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Glucagon and Lipoprotein Regulation in Man

  • R. P. Eaton

Abstract

We have proposed that reduced glucagon activity may participate in the induction and/or maintenance of acquired as well as genetically determined endogenous hyperlipemia. To critically consider this hypothesis, the physiologic response to glucagon must be evaluated in a variety of clinical conditions in which the glucagon-lipid axis may be altered. Moreover, in this process, the critical role of free fatty acid availability, simultaneous insulin secretion, and concurrent production of the counter-regulatory hormones cortisol, growth hormone and catecholamines must be considered. Therefore, in the present review, the lipoprotein response to glucagon is examined in normal subjects, insulin-deficient diabetic subjects, insulin-resistant obese subjects and glucagon-resistant hyperlipemic subjects. In addition, the alterations in glucagon secretion induced by “estrogen hyperlipemia” and clofibrate “hypolipemia” are considered in relation to the hypothesis that glucagon deficiency may lead to hyperlipemia, while glucagon excess may reduce plasma lipids. A basic function of glucagon in augmenting free fatty acid availability to the liver while simultaneously “shifting” hepatic fatty acid metabolism into oxidative pathways of ketogenesis and away from synthetic pathways of lipoprotein production, is suggested as the critical axis of altered metabolism in the many pathologic conditions in which disturbed lipid physiology is recognized.

Keywords

Growth Hormone Glucagon Secretion Endogenous Insulin Secretion Plasma Triglyceride Concentration Free Fatty Acid Metabolism 
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.

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References

  1. 1.
    Amatuzio, D. S., Grande, F. and Wada, S. (1962): Effect of glucagon on the serum lipids in essential hyperlipemia and in hypercholesterolemia. Metabolism 11, 1240–1249.PubMedGoogle Scholar
  2. 2.
    Bagdade, J. D., Porte, D., Bierman, E. (1967): Diabetic lipemia. N. Eng. J. Med. 276, 427–433.CrossRefGoogle Scholar
  3. 3.
    Bagdade, J. D., Yee, E., Alberts, J. and Pykalisto, O. J. (1976): Gluco-corticoids and triglyceride transport: Effects on triglyceride secretion rates, lipoprotein lipase, and plasma lipoproteins in the rat. Metabolism 25, 533–542.Google Scholar
  4. 4.
    Beck, P., Eaton, R. P., Arnett, D. M. and Alsever, R. N. (1975): Effect of contraceptive steroids on arginine-stimulated glucagon and insulin secretion in women: I-Lipid physiology. Metabolism 24, 1055–1065.PubMedCrossRefGoogle Scholar
  5. 5.
    De Oya, M., Prigge, W. F. and Grande, F. (1971): Suppression by hepatectomy of glucagon-induced hypertriglyceridemia in geese. Proc. Soc. Exp. Biol. Med. 136, 107–110.Google Scholar
  6. 6.
    Eaton, R. P., Berman, M. and Steinberg, D. (1969): Kinetic studies of plasma free fatty acid and triglyceride metabolism in man. J. Clin. Invest. 48, 1560–1579.PubMedCrossRefGoogle Scholar
  7. 7.
    Eaton, R. P. and Schade, D. S. (1973): Hypothesis: “Glucagon Resistance”: An hormonal basis for endogenous hyperlipemia. Lancet 1, 973–974.Google Scholar
  8. 8.
    Eaton, R. P. and Schade, D. S. (1974): The effect of clofibrate on arginine stimulated glucagon and insulin secretion in man. Metabolism 23, 445–454.PubMedCrossRefGoogle Scholar
  9. 9.
    Eaton, R. P. and Schade, D. S. (1977): The modulation and implications of the counter-regulatory hormones, glucagon, catecholamines, cortisol, and growth hormone in diabetes, obesity, and hyperlipemia. In: Adv. Modern Nutr. 2, 341–372.Google Scholar
  10. 10.
    Eaton, R. P., Schade, D. S. and Conway, M. (1974): Hypothesis: Decreased glucagon activity: A mechanism for both genetic and acquired hyperlipemia. Lancet 2, 1545–1548.Google Scholar
  11. 11.
    Felig, P., Marliss, E. B. and Cahill, G. F., Jr. (1971): Metabolic response to human growth hormone during prolonged starvation. J. Clin. Invest. 50, 411–421.Google Scholar
  12. 12.
    Friedman, M., Byers, S. O., Rosenman, R. H., Li, C. G. and Neuman, R. (1974): Effect of subacute administration of human growth hormone on various serum lipid and hormone levels of hypercholesterolemic and normocholesterolemic subjects. Metabolism 23, 905–912.PubMedCrossRefGoogle Scholar
  13. 13.
    Heimberg, M., Fizette, N. B. and Klausner, H. (1964): The action of adrenal hormones on hepatic transport of triglycerides and fatty acids. J. Amer. Oil Chem. Soc. 41, 774–779.Google Scholar
  14. 14.
    Marco, J., Calle, C., Roman, D., Diaz-Fierros, M., Villanueva, M. L. and Valverde, I. (1973): Hyperglucagonism induced by glucocorticoid treatment in man. N. Engl. J. Med. 288, 128–132.Google Scholar
  15. 15.
    Merimee, T. J., Hollander, W., Fineberg, S. E. (1972): Studies of hyperlipidemia in the HGH-deficient state. Metabolism 21, 1053–1061.PubMedCrossRefGoogle Scholar
  16. 16.
    Pek, S., Fajans, S. S., Floyd, J. C. and Knopf, R. F. (1973): Clinical conditions associated with elevated plasma levels of glucagon. Proceedings, International Diabetes Federation, VIII Congress, pp. 207–213.Google Scholar
  17. 17.
    Reaven, E. and Reaven, G. M. (1974): Mechanisms for development of diabetic hypertriglyceridemia in streptozotocin-treated rats. Effect of diet and duration of insulin deficiency. J. Clin. Invest. 54, 1167–1178.Google Scholar
  18. 18.
    Sailer, S., Sandhofer, F. and Braunsteiner, H. (1966): Umsatzraten fur freie Fettsauren und Triglyceride im Plasma bei essentieller Hyperlipamie. Klin. Wschr. 44, 1032–1036.Google Scholar
  19. 19.
    Schade, D. S. and Eaton, R. P. (1975): Modulation of fatty acid metabolism by glucagon in man. Diabetes 24, 502–509.PubMedCrossRefGoogle Scholar
  20. 20.
    Schade, D. S. and Eaton, R. P. (1975): Modulation of fatty acid metabolism by glucagon in man. II. Effects in insulin deficient diabetes. Diabetes 24, 510–515.Google Scholar
  21. 21.
    Schade, D. S. and Eaton, R. P. (1975): The contribution of endogenous insulin secretion to the ketogenic response to glucagon in man. Diabetologia 11, 555–559.PubMedCrossRefGoogle Scholar
  22. 22.
    Schade, D. S. and Eaton, R. P. (1977): Modulation of the catabolic activity of glucagon by endogenous insulin secretion in obese man. Acta Diabetol. Latina (in press).Google Scholar
  23. 23.
    Sherwin, R. S., Fisher, M., Hendler, R. and Felig, P. (1976): Hypergluca-gonemia and blood glucose regulation in normal, obese, and diabetic subjects. N. Engl. J. Med. 294, 455–561.Google Scholar
  24. 24.
    Willms, B., Böttcher, M., Wolters, V., Sakamoto, N. and Söling, H. D. (1969) Relationship between fat and ketone metabolism in obese and non-obese diabetics and non-diabetics during norepinephrine infusion. Diabetologia. 5, 88–96.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 1977

Authors and Affiliations

  • R. P. Eaton
    • 1
  1. 1.University of New Mexico School of MedicineAlbuquerqueUSA

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