Skip to main content
SpringerLink
Log in
Book cover

GLUCAGON: Its Role in Physiology and Clinical Medicine pp 517–532Cite as

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

  • Conference paper

Abstract

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.

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. 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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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. 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. 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. Byers, S. O., Friedman, M. and Elek, S. R. (1975): Further studies concerning glucagon-induced hypocholesterolemia. Proc. Soc. Exp. Biol. Med. 149, 151–157.

    PubMed  CAS  Google Scholar 

  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. Eaton, R. P. (1973): Hypolipemic action of glucagon in experimental endogenous lipemia in the rat. J. Lipid Res. U, 312–318.

    Google Scholar 

  9. Eaton, R. P. (1973): Effect of clofibrate on arginine-induced insulin and glucagon secretion. Metabolism 2£, 763–767.

    Google Scholar 

  10. Eaton, R. P. (1977): Glucagon and lipoprotein regulation in man. This volume, p. 533–550.

    Google Scholar 

  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. 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.

    Article  PubMed  CAS  Google Scholar 

  13. Eaton, R. P. and Schade, D. S. (1973): Glucagon resistance as a hormonal basis for endogenous hyperlipemia. Lancet 1, 973–974.

    Article  PubMed  CAS  Google Scholar 

  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. Eaton, R. P. and Schade, D. S. (1974): Effect of clofibrate on arginine- stimulated glucagon and insulin secretion in man. Metabolism 23, 445–454.

    Article  PubMed  CAS  Google Scholar 

  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. 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.

    PubMed  CAS  Google Scholar 

  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. Foa, P. P. (1968): Glucagon. Rev. Physiol. Biochem. Exper. Pharmacol. 60 141–219.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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. Gey, K. F. and Georgi, H. Unpublished data.

    Google Scholar 

  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. Haugaard, E. S. and Haugaard, N. (1954): The effect of hyperglycemic- glycogenolytic factor on fat metabolism of liver. J. Biol. Chem. 206, 641–645.

    PubMed  CAS  Google Scholar 

  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. 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.

    PubMed  CAS  Google Scholar 

  27. Kraml, M. (1966): A semi-automated determination of phospholipids. Clin. Chim. Acta. 13., 442–448.

    Google Scholar 

  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. Lorch, E. and Gey, K. F. (1966): Photometric “titration” of free fatty acids with the technicon autoanalyzer. Anal. Biochem. 244–252.

    Google Scholar 

  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. 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. 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. 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. 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.

    PubMed  CAS  Google Scholar 

  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. 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.

    PubMed  CAS  Google Scholar 

  37. Roche Diagnostica Procedure: System CentrifiChem®, Prod. No. 1405. (Glucose HK/G6P-DH).

    Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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. Royer, M. E. and Ko, H. (1969): A simplified semiautomated assay for plasma triglycerides. Anal. Biochem. 29, 405–416.

    Article  PubMed  CAS  Google Scholar 

  41. Salter, J. M. (1960): Metabolic effects of glucagon in the Wistar rat. Amer. J. Clin. Nutr. 8, 535–539.

    CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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. 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. 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. 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 

Download references

Author information

Authors and Affiliations

  1. Research Departments, F. Hoffmann-La Roche and Co. Ltd., 4002, Basel, Switzerland

    F. Gey, H. Georgi & E. Buhler

Authors
  1. F. Gey
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. Georgi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. Buhler
    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

Gey, F., Georgi, H., Buhler, E. (1977). Lowering of Plasma Lipids, The Major Effect of Repeated Glucagon Administration in Rats. 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_33

Download citation

  • DOI: https://doi.org/10.1007/978-1-4612-6366-1_33

  • 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