Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1973 Nov;52(11):2774–2782. doi: 10.1172/JCI107473

Influence of Glucocorticoids on Glucagon Secretion and Plasma Amino Acid Concentrations in Man

Jonathan K Wise 1, Rosa Hendler 1, Philip Felig 1
PMCID: PMC302545  PMID: 4748510

Abstract

Plasma concentrations of glucagon, insulin, glucose, and individual plasma amino acids were measured in normal nonobese and obese subjects before and after 3 days of dexamethasone treatment (2 mg/day) and in patients with Cushing's syndrome. The subjects were studied in the basal postabsorptive state and following the infusion of alanine (0.15 g/kg) or ingestion of a protein meal.

In nonobese subjects dexamethasone treatment resulted in a 55% increment in basal glucagon levels and in a 60-100% increase in the maximal glucagon response to alanine infusion or protein ingestion. In obese subjects, basal glucagon rose by 110% following dexamethasone, while the response to alanine increased fourfold. In patients with Cushing's syndrome basal glucagon levels were 100% higher and the glucagon response to alanine infusion was 170% greater than in normal controls.

Dexamethasone treatment in normal subjects resulted in a 40% rise in plasma alanine concentration which was directly proportional to the rise in basal glucagon. The remaining 14 amino acids were unchanged. In the patients with Cushing's syndrome alanine levels were 40% higher than in normal controls and were directly proportional to basal glucagon concentrations. No other plasma amino acids were significantly altered in the group with Cushing's syndrome.

It is concluded that (a) glucocorticoids increase plasma glucagon concentration in the basal state and in response to protein ingestion or aminogenic stimulation; (b) this effect of glucocorticoids occurs in the face of obesity and persists in chronic hypercorticism; (c) hyperalaninemia is a characteristic of acute and chronic glucocorticoid excess, and may in turn contribute to steroid-induced hyperglucagonemia; and (d) increased alpha cell secretion may be a contributory factor in the gluconeogenic and diabetogenic effects of glucocorticoids.

Full text

PDF
2774

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aguilar-Parada E., Eisentraut A. M., Unger R. H. Pancreatic glucagon secretion in normal and diabetic subjects. Am J Med Sci. 1969 Jun;257(6):415–419. doi: 10.1097/00000441-196906000-00008. [DOI] [PubMed] [Google Scholar]
  2. Block W. D., Markovs M. E., Steele B. F. Comparison between free amino acid levels in plasma deproteinated with picric acid and with sulfosalicylic acid. Proc Soc Exp Biol Med. 1966 Aug-Sep;122(4):1089–1091. doi: 10.3181/00379727-122-31333. [DOI] [PubMed] [Google Scholar]
  3. Cahill G. F., Jr Glucagon. N Engl J Med. 1973 Jan 18;288(3):157–158. doi: 10.1056/NEJM197301182880313. [DOI] [PubMed] [Google Scholar]
  4. Eisenstein A. B., Spencer S., Flatness S., Brodsky A. Carbohydrate synthesis in the isolated perfused rat liver: role of the adrenal cortex. Endocrinology. 1966 Jul;79(1):182–186. doi: 10.1210/endo-79-1-182. [DOI] [PubMed] [Google Scholar]
  5. Exton J. H., Friedmann N., Wong E. H., Brineaux J. P., Corbin J. D., Park C. R. Interaction of glucocorticoids with glucagon and epinephrine in the control of gluconeogenesis and glycogenolysis in liver and of lipolysis in adipose tissue. J Biol Chem. 1972 Jun 10;247(11):3579–3588. [PubMed] [Google Scholar]
  6. Felig P., Pozefsky T., Marliss E., Cahill G. F., Jr Alanine: key role in gluconeogenesis. Science. 1970 Feb 13;167(3920):1003–1004. doi: 10.1126/science.167.3920.1003. [DOI] [PubMed] [Google Scholar]
  7. Felig P. The glucose-alanine cycle. Metabolism. 1973 Feb;22(2):179–207. doi: 10.1016/0026-0495(73)90269-2. [DOI] [PubMed] [Google Scholar]
  8. Felig P., Wahren J. Amino acid metabolism in exercising man. J Clin Invest. 1971 Dec;50(12):2703–2714. doi: 10.1172/JCI106771. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Felig P., Wahren J., Hendler R., Ahlborg G. Plasma glucagon levels in exercising man. N Engl J Med. 1972 Jul 27;287(4):184–185. doi: 10.1056/NEJM197207272870412. [DOI] [PubMed] [Google Scholar]
  10. HENNES A. R., WAJCHENBERG B. L., FAJANS S. S., CONN J. W. The effect of adrenal steroids on blood levels of pyruvic and alpha-ketoglutaric acids in normal subjects. Metabolism. 1957 Jul;6(4):339–345. [PubMed] [Google Scholar]
  11. HUGGETT A. S., NIXON D. A. Use of glucose oxidase, peroxidase, and O-dianisidine in determination of blood and urinary glucose. Lancet. 1957 Aug 24;273(6991):368–370. doi: 10.1016/s0140-6736(57)92595-3. [DOI] [PubMed] [Google Scholar]
  12. Hollifield G. Glucocorticoid-induced obesity--a model and a challenge. Am J Clin Nutr. 1968 Dec;21(12):1471–1474. doi: 10.1093/ajcn/21.12.1471. [DOI] [PubMed] [Google Scholar]
  13. MOORE S., STEIN W. H. A modified ninhydrin reagent for the photometric determination of amino acids and related compounds. J Biol Chem. 1954 Dec;211(2):907–913. [PubMed] [Google Scholar]
  14. Mackrell D. J., Sokal J. E. Antagonism between the effects of insulin and glucagon on the isolated liver. Diabetes. 1969 Nov;18(11):724–732. doi: 10.2337/diab.18.11.724. [DOI] [PubMed] [Google Scholar]
  15. Marco J., Calle C., Román D., Díaz-Fierros M., Villanueva M. L., Valverde I. Hyperglucagonism induced by glucocorticoid treatment in man. N Engl J Med. 1973 Jan 18;288(3):128–131. doi: 10.1056/NEJM197301182880305. [DOI] [PubMed] [Google Scholar]
  16. Munck A. Glucocorticoid inhibition of glucose uptake by peripheral tissues: old and new evidence, molecular mechanisms, and physiological significance. Perspect Biol Med. 1971 Winter;14(2):265–269. doi: 10.1353/pbm.1971.0002. [DOI] [PubMed] [Google Scholar]
  17. Müller W. A., Faloona G. R., Unger R. H. The effect of alanine on glucagon secretion. J Clin Invest. 1971 Oct;50(10):2215–2218. doi: 10.1172/JCI106716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pagliara A. S., Kari I. E., De Vivo D. C., Feigin R. D., Kipnis D. M. Hypoalaninemia: a concomitant of ketotic hypoglycemia. J Clin Invest. 1972 Jun;51(6):1440–1449. doi: 10.1172/JCI106940. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Perley M., Kipnis D. M. Effect of glucocorticoids on plasma insulin. N Engl J Med. 1966 Jun 2;274(22):1237–1241. doi: 10.1056/NEJM196606022742205. [DOI] [PubMed] [Google Scholar]
  20. RYAN W. L., CARVER M. J. IMMEDIATED AND PROLONGED EFFECTS OF HYDROCORTISONE ON THE FREE AMINO ACIDS OF RAT SKELETAL MUSCLE. Proc Soc Exp Biol Med. 1963 Dec;114:816–819. doi: 10.3181/00379727-114-28808. [DOI] [PubMed] [Google Scholar]
  21. Rosselin G., Assan R., Yalow R. S., Berson S. A. Separation of antibody-bound and unbound peptide hormones labelled with iodine-131 by talcum powder and precipitated silica. Nature. 1966 Oct 22;212(5060):355–357. doi: 10.1038/212355a0. [DOI] [PubMed] [Google Scholar]
  22. STEIN W. H., MOORE S. The free amino acids of human blood plasma. J Biol Chem. 1954 Dec;211(2):915–926. [PubMed] [Google Scholar]
  23. Smith O. K., Long C. N. Effect of cortisol on the plasma amino nitrogen of eviscerated adrenalectomized-diabetic rats. Endocrinology. 1967 Apr;80(4):561–566. doi: 10.1210/endo-80-4-561. [DOI] [PubMed] [Google Scholar]
  24. Unger R. H. Glucagon physiology and pathophysiology. N Engl J Med. 1971 Aug 19;285(8):443–449. doi: 10.1056/NEJM197108192850806. [DOI] [PubMed] [Google Scholar]
  25. Unger R. H., Ohneda A., Aguilar-Parada E., Eisentraut A. M. The role of aminogenic glucagon secretion in blood glucose homeostasis. J Clin Invest. 1969 May;48(5):810–822. doi: 10.1172/JCI106039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Wise J. K., Hendler R., Felig P. Evaluation of alpha-cell function by infusion of alanine in normal, diabetic and obese subjects. N Engl J Med. 1973 Mar 8;288(10):487–490. doi: 10.1056/NEJM197303082881003. [DOI] [PubMed] [Google Scholar]
  27. Wise J. K., Hendler R., Felig P. Obesity: evidence of decreased secretion of glucagon. Science. 1972 Nov 3;178(4060):513–514. doi: 10.1126/science.178.4060.513. [DOI] [PubMed] [Google Scholar]
  28. ZINNEMAN H. H., JOHNSON J. J., SEAL U. S. EFFECT OF SHORT-TERM THERAPY WITH CORTISOL ON THEURINARY EXCRETION OF FREE AMINO ACIDS. J Clin Endocrinol Metab. 1963 Oct;23:996–1000. doi: 10.1210/jcem-23-10-996. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES