Lowering of Plasma Lipids, The Major Effect of Repeated Glucagon Administration in Rats

  • F. Gey
  • H. Georgi
  • E. Buhler


The most prominent long lasting effect of repeated injection of commercial pancreatic glucagon (0.1–30 mg/kg s.c. twice daily) in fed and starving rats is a depression of the major plasma lipids. This lipid-lowering effect of glucagon becomes maximal after 2–3 days and persists for at least 4 weeks. After withdrawal of glucagon, the lipid levels, slowly return to normal. Plasma lipid depression occurs at glucagon doses (0.1 mg/kg) which have no comparable long-lasting effect on the level of other plasma components, such as glucose, FFA, α-amino nitrogen and urea, as well as on urinary excretion of urea. Dose-frequency curves suggest that lipid depression could also be obtained by the frequent release of small pulses of endogenous glucagon. On a molar basis, glucagon is more potent than other lipid-lowering hormones, like thyroxine and oestradiol. The injection of glucagon leads to a marked increase of the glucagon/insulin ratio in plasma, in spite of a considerable insulin release. Experiments in streptozotocin-treated rats with fully developed diabetes demonstrate that the lipid depression by glucagon does not depend on insulin. In consequence, a role of glucagon in the physiologic regulation of plasma lipids in the rat is suggested.


Plasma Lipid Plasma Cholesterol Plasma Glucagon Pancreatic Glucagon Glucagon Administration 
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  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.
    Aubry, F., Marcel, Y. L. and Davignon, J. (1974): Effects of glucagon on plasma lipids in different types of primary hyperlipoproteinemia. Metabolism 23, 225–238.PubMedCrossRefGoogle Scholar
  3. 3.
    Berthet, J. (1958): Action du glucagon et de VadrSnaline sur le metabolisme des lipides dans le tissu hepatique. In: Proceedings, IV International Congress of Biochemistry, Vienna. Pergamon Press, London, p. 107.Google Scholar
  4. 4.
    Block, W. D., Jarrett, K. J., Jr. and Levine, J. B. (1966): Use of a single color reagent to improve the automated determination of serum total cholesterol. In: Automation in Analytical Chemistry: Technicon Symposium 1965. L. T. Skeggs Jr., Ed. Mediad Incorporated, New York, pp. 345–347.Google Scholar
  5. 5.
    Bloxham, D. P. and Akhtar, M. (1971): Studies on the control of cholesterol biosynthesis: the adenosine 3′,5′-cyclic monophosphate-dependent accumulation of a steroid carboxylic acid. Biochem. J. 123, 275–278.Google Scholar
  6. 6.
    Byers, S. O., Friedman, M. and Elek, S. R. (1975): Further studies concerning glucagon-induced hypocholesterolemia. Proc. Soc. Exp. Biol. Med. 149, 151–157.PubMedGoogle Scholar
  7. 7.
    Cahill, G. F. Jr. and Aoki, T. T. (1977): The role of glucagon in amino acid homeostasis. This volume, p. 487–494.Google Scholar
  8. 8.
    Eaton, R. P. (1973): Hypolipemic action of glucagon in experimental endogenous lipemia in the rat. J. Lipid Res. U, 312–318.Google Scholar
  9. 9.
    Eaton, R. P. (1973): Effect of clofibrate on arginine-induced insulin and glucagon secretion. Metabolism 2£, 763–767.Google Scholar
  10. 10.
    Eaton, R. P. (1977): Glucagon and lipoprotein regulation in man. This volume, p. 533–550.Google Scholar
  11. 11.
    Eaton, R. P., Conway, M. and Schade, D. S. (1976): Endogenous glucagon regulation in genetically hyperlipemic obese rats. Am. J. Physiol. 230, 1336–1340.Google Scholar
  12. 12.
    Eaton, R. P., Oase, R. and Schade, D. S. (1976): Altered insulin and glucagon secretion in treated genetic hyperlipemia: a mechanism of therapy? Metabolism 25, 245–249.PubMedCrossRefGoogle Scholar
  13. 13.
    Eaton, R. P. and Schade, D. S. (1973): Glucagon resistance as a hormonal basis for endogenous hyperlipemia. Lancet 1, 973–974.PubMedCrossRefGoogle Scholar
  14. 14.
    Eaton, R. P. and Schade, D. S. (1973): Clofibrate suppression of insulin/ glucagon secretory ratio in man. Clin. Res. 21, 273.Google Scholar
  15. 15.
    Eaton, R. P. and Schade, D. S. (1974): Effect of clofibrate on arginine- stimulated glucagon and insulin secretion in man. Metabolism 23, 445–454.PubMedCrossRefGoogle Scholar
  16. 16.
    Exton, J. H., Corbin, J. G. and Harper, S. C. (1972): Control of gluconeo- genesis in liver. V. Effects of fasting, diabetes, and glucagon on lactate and endogenous metabolism in the perfused rat liver. J. Biol. Chem. 247, 4996–5003.Google Scholar
  17. 17.
    Exton, J. H. and Park, C. R. (1967): Control of gluconeogenesis in liver. I. General features of gluconeogenesis in the perfused livers of rats. J. Biol. Chem. 242, 2622–2636.PubMedGoogle Scholar
  18. 18.
    Faloona, G. R. and Unger, H. (1974): Glucagon. In: Methods of Hormone Radioimmunoassay. B. M. Jaffe and H. R. Behrmann, Eds. Academic Press, New York, pp. 317–330.Google Scholar
  19. 19.
    Foa, P. P. (1968): Glucagon. Rev. Physiol. Biochem. Exper. Pharmacol. 60 141–219.CrossRefGoogle Scholar
  20. 20.
    Friedman, M., Byers, S. 0., Rosenman, R. H. and Elek, S. (1971): Effect of glucagon on blood-cholesterol levels in rats. Lancet 2, 464–466.PubMedCrossRefGoogle Scholar
  21. 21.
    Gerich, J. E., Langlois, M., Schneider, V., Karam, J. H. and Noacco, C. (1974): Effects of alterations of plasma free fatty acid levels on pancreatic glucagon secretion in man. J. Clin. Invest. 53, 1284–1289.Google Scholar
  22. 22.
    Gey, K. F. and Georgi, H. Unpublished data.Google Scholar
  23. 23.
    Gorman, C. K., Salter, J. M. and Penhos, J. C. (1967): Effects of glucagon on lipids and glucose in normal and eviscerated rats and on isolated perfused rat livers. Metabolism 1140–1157.Google Scholar
  24. 24.
    Haugaard, E. S. and Haugaard, N. (1954): The effect of hyperglycemic- glycogenolytic factor on fat metabolism of liver. J. Biol. Chem. 206, 641–645.PubMedGoogle Scholar
  25. 25.
    Haugaard, E. S. and Stadie, W. C. (1953): The effect of hyperglycemic- glycogenolytic factor and epinephrine on fatty acid synthesis. J. Biol. Chem. 200, 753–757.Google Scholar
  26. 26.
    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.PubMedGoogle Scholar
  27. 27.
    Kraml, M. (1966): A semi-automated determination of phospholipids. Clin. Chim. Acta. 13., 442–448.Google Scholar
  28. 28.
    Lakshmanan, M. R., Nepokroeff, C. M. and Porter, J. W. (1972): Control of the synthesis of fatty acid synthetase in rat liver by insulin, glucagon, and adenosine 3′,5′-cyclic monophosphate. Proc. Nat. Acad. Sci. USA 69, 3516–3519.Google Scholar
  29. 29.
    Lorch, E. and Gey, K. F. (1966): Photometric “titration” of free fatty acids with the technicon autoanalyzer. Anal. Biochem. 244–252.Google Scholar
  30. 30.
    Marks, V., Frizel, D., Twycross, R. G. and Buchanan, K. D. (1971): Effect of 3-pyridylcarbinol on glucose tolerance, plasma glucagon, insulin, and growth hormone in man. In: Metabolic Effects of Nicotinic Acid and its Derivatives. K. F. Gey and L. A. Carlson, Eds. Hans Huber Verlag, Bern, pp. 961–976.Google Scholar
  31. 31.
    Marsh, W. H., Fingerhut, B. and Kirsch, E. (1957): Determination of urea nitrogen with the diacetyl method and an automatic dialyzing apparatus. Amer. J. Clin. Path. 28, 681–688.Google Scholar
  32. 32.
    Meikle, A. W., Klain, G. J. and Hannon, J. P. (1973): Inhibition of glucose oxidation and fatty acid synthesis in liver slices from fed, fasted and fasted-refed rats by glucagon, epinephrine and cyclic adenosine-31,5- monophosphate. Proc. Soc. Exp. Biol. Med. M3, 379–381.Google Scholar
  33. 33.
    Nepokroeff, C. M., Lakshmanan, M. R., Ness, G. C., Dugan, R. E. and Porter, J. W. (1974): Regulation of the diurnal rhythm of rat liver β-hydroxy-β- methyl-glutaryl coenzyme A reductase activity by insulin, glucagon, cyclic AMP and hydrocortisone. Arch. Biochem. Biophys. 160, 387–396.Google Scholar
  34. 34.
    Palmer, D. W. and Peters, T. Jr. (1969): Automated determination of free amino groups in serum and plasma using 2, 4, 6-trinitrobenzene sulfonate. Clin. Chem. 15, 891–901.PubMedGoogle Scholar
  35. 35.
    Paloyan, E., Dumbrys, N., Gallagher, T. F. Jr., Rodgers, R. E. and Harper, P. V. (1962): The effect of glucagon on hyperlipemic states. Fed. Proc. 21, 200.Google Scholar
  36. 36.
    Penhos, J. C., Wu, C. H., Daunas, J., Reitman, M. and Levine, R. (1966): Effect of glucagon on the metabolism of lipids and on urea formation by the perfused rat liver. Diabetes 15, 740–748.PubMedGoogle Scholar
  37. 37.
    Roche Diagnostica Procedure: System CentrifiChem®, Prod. No. 1405. (Glucose HK/G6P-DH).Google Scholar
  38. 38.
    Rothfeld, B., Margolis, S., Varady, A. Jr. and Karmen, A. (1974): Effects of glucagon on cholesterol and triglyceride deposition in tissues. Biochem. Med. 10, 122–125.PubMedCrossRefGoogle Scholar
  39. 39.
    Rothfeld, B., Pare, W. P., Margolis, S., Karmen, A., Varady, A. Jr. and Isom, K. E. (1974): Effect of glucagon and stress on cholesterol metabolism and deposition in tissues. Biochem. Med. 11, 189–193.Google Scholar
  40. 40.
    Royer, M. E. and Ko, H. (1969): A simplified semiautomated assay for plasma triglycerides. Anal. Biochem. 29, 405–416.PubMedCrossRefGoogle Scholar
  41. 41.
    Salter, J. M. (1960): Metabolic effects of glucagon in the Wistar rat. Amer. J. Clin. Nutr. 8, 535–539.Google Scholar
  42. 42.
    Schade, D. S. and Eaton, R. P. (1975): Modulation of fatty acid metabolism by glucagon in man. I. Effects in normal subjects. Diabetes 24, 502–509.PubMedCrossRefGoogle Scholar
  43. 43.
    Schade, D. S. and Eaton, R. P. (1975): Modulation of fatty acid metabolism by glucagon in man. II. Effects in insulin-deficient diabetics. Diabetes 24, 510–515.Google Scholar
  44. 44.
    Stauffacher, W., Assan, R., Gey, K. F. and Renold, A. E. (1971): Effects of 3-pyridylcarbinol on levels of immunoreactive insulin and glucagon in pancreas and blood of intact rats. In: Metabolic Effects of Nicotinic Acid and its Derivatives. K. F. Gey and L. A. Carlson, Eds. Hans Huber Verlag, Bern, pp. 987–994.Google Scholar
  45. 45.
    Unger, R. H. (1972): Glucagon and glucagon immunoreactivity in plasma and pancreatic tissues. In: Glucagon. Molecular Physiology, Clinical and Therapeutic Implications. P. J. Leffebvre and R. H. Unger, Eds. Pergamon Press, New York, pp. 205–211.Google Scholar
  46. 46.
    Weinstein, I., Klausner, H. A. and Heimberg, M. (1973): The effect of concentration of glucagon on output of triglyceride, ketone bodies, glucose, and urea by the liver. Biochim. Biophys. Acta 296, 300–309.Google Scholar

Copyright information

© Springer-Verlag New York Inc. 1977

Authors and Affiliations

  • F. Gey
    • 1
  • H. Georgi
    • 1
  • E. Buhler
    • 1
  1. 1.Research DepartmentsF. Hoffmann-La Roche and Co. Ltd.BaselSwitzerland

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