Skip to main content
Log in

Effect of indomethacin on the metabolic and hormonal response to a standardized breakfast in normal subjects

  • Original Contributions
  • Published:
Acta diabetologia latina Aims and scope Submit manuscript

Summary

We have investigated the influence of a single oral administration of indomethacin on blood glucose, plasma free fatty acids (FFA), α-amino-nitrogen, insulin and glucagon concentrations in young healthy subjects. Two groups of 6 subjects were studied, the first received a standardized 500 kcal mixed meal without any previous drug administration (controls) whereas the second group received 50 mg indomethacin 2 h before ingesting an identical meal. Plasma indomethacin concentration reached its maximum (2.36±0.36 Μg/ml) 15 min after administration and declined to 0.45±0.04 ug/ml after 2 h. Indomethacin ingestion was followed by a significant increase in blood glucose and plasma FFA reaching their maximum value at 45 min and returning to basal levels at 120 min. No simultaneous changes in plasma α-amino-nitrogen, insulin or glucagon levels were detected during this period. The meal was followed by a rise in blood glucose and plasma insulin as well as by a decrease in plasma FFA concentration. No significant differences were detected between the controls and the subjects receiving indomethacin. In controls, the meal was followed by a rise in plasma α-amino-nitrogen and a modest although significant increase in glucagon levels. In indomethacin-treated subjects, the increment of α-amino-nitrogen was less marked and the increase in plasma glucagon was not observed. Thus, indomethacin by itself can exert several metabolic effects; however, it does not deteriorate the blood glucose or insulin profile after a regular meal. The present work is the first to demonstrate that an inhibitor of prostaglandin synthesis inhibits the plasma glucagon rise occurring after a physiological stimulus such as a normal meal. On the basis of previousin vitro experiments, we suggest that this effect results from an inhibition of glucagon secretion by the PG synthesis inhibitor.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Aronoff S. L., Kipnis D. M.: Effects of indomethacin (INDO) on insulin secretion by tissue cultured-perifused rat islets - Diabetes27 (Suppl. 2), 457, 1978; abstract # 108.

    Google Scholar 

  2. Brodows R. G.: Endogenous prostaglandins as insulin secretagogues; effects of indomethacin (INDO) on basal, glucose and arginine stimulated insulin release in man - Clin. Res.26, 677a, 1978.

    Google Scholar 

  3. Brodows R. S.: Acute alterations in prostaglandin status fail to influence insulin secretion in man - Diabetes29 (Suppl. 2), 9A, 1980; abstract #34.

    Google Scholar 

  4. Bybee D. E., Broadie T. R., Georges L. P., Fletcher J. R., Diaz M. J., O'Brien J. T.: Indomethacin induced augmentation of insulin and glucagon release - Diabetes27 (Suppl. 2), 470, 1978; abstract #157.

    Google Scholar 

  5. Cavagnini F., Di Landro A., Invitti C., Raggi U., Alessandrini P., Pinto M., Girotti G., Vigo P.: Effects of acetylsalicylic acid and indomethacin on growth hormone secretion in man - Metabolism26, 193, 1977.

    Article  PubMed  Google Scholar 

  6. Chen M., Robertson R. P.: Effects of prostaglandin synthesis inhibitors on human insulin secretion and carbohydrate tolerance - Prostaglandins18, 557, 1979.

    Article  PubMed  Google Scholar 

  7. Dalton C., Hope H. H.: Inability of prostaglandin synthesis inhibition to affect adipose tissue lipolysis - Prostaglandins4, 641, 1973.

    PubMed  Google Scholar 

  8. Dole V. P., Meinertz H.: Microdetermination of long chain fatty acids in plasma and tissues - J. biol. Chem.235, 2395, 1960.

    Google Scholar 

  9. Dray F., Kouznetzova B., Harris D., Brazeau P.: Role of prostaglandins on growth hormone secretion: PGE2 a physiological stimulator - In:Samuelsson B., Ramwell P. W., Paoletti R. (Eds): Advances in prostaglandins and thromboxane research, Vol. 8. Raven Press, New York, 1980; p. 1321.

    Google Scholar 

  10. Fain J. N., Psychoyas S., Czernik A. J., Frost S., Cash W. D.: Indomethacin, lipolysis and cyclic AMP accumulation in white fat cells - Endocrinology93, 632, 1973.

    PubMed  Google Scholar 

  11. Ganguli S., Sperling M. A., Frame C., Christensen R.: Inhibition of glucagon-induced hepatic glucose production by indomethacin - Amer. J. Physiol.236, E 358, 1979.

    Google Scholar 

  12. Gerich J. E., Lorenzi M., Karam J. H., Schneider V., Forsham P. H.: Abnormal pancreatic glucagon secretion and postprandial hyperglycemia in diabetes mellitus - J. Amer. med. Ass.234, 159, 1975.

    Article  Google Scholar 

  13. Giugliano D., Torella R., Siniscalchi N., Improta L., D'Onofrio F.: The effect of acetylsalicylic acid on insulin response to glucose and arginine in normal man - Diabetologia14, 359, 1978.

    Article  PubMed  Google Scholar 

  14. Hales C. N., Randle P. J.: Immunoassay of insulin with insulin-antibody precipitate - Biochem. J.88, 137, 1963.

    PubMed  Google Scholar 

  15. Holt L. P. J., Hawkins C. F.: Indomethacin: studies of absorption and of the use of indomethacin suppositories - Brit. med. J.1, 1354, 1965.

    Google Scholar 

  16. Hvidberg E., Lausen H., Jansen J. A.: Indomethacin: plasma concentrations and protein binding in man - Europ. J. clin. Pharmacol.4, 119, 1972.

    Article  Google Scholar 

  17. Illiano S., Cuatrecasas P.: Endogenous prostaglandins modulate lipolytic processes in adipose tissue. Nature (Lond.)234, 72, 1971.

    Google Scholar 

  18. Lefebvre P., Luyckx A. S.: The breakfast tolerance test: a return to physiology - Diab. Metab.2, 15, 1976.

    Google Scholar 

  19. Lefebvre P., Luyckx A. S.: Glucagon and diabetes: a reappraisal - Diabetes16, 347, 1979.

    Google Scholar 

  20. Lefebvre P., Luyckx A. S.: Glucagon - In:Gray C. H., James V. H. T. (Eds): Hormones in blood. 3rd ed. Academic Press, New York-London 1979; p. 171.

    Google Scholar 

  21. Luyckx A. S.: Immunoassays for glucagon - In:Lefebvre P. J., Unger R. H. (Eds): Glucagon: molecular physiology, clinical and therapeutic implications. Pergamon Press, Oxford, 1972; p. 285.

    Google Scholar 

  22. Luyckx A. S., Deliege M., Jardon-Jeghers C., Lefebvre P. J.: Insulin, prostaglandin E2 and glucagon release by human insuloma tissue incubatedin vitro. Influence of indomethacin - Diab. Metab.7, 13, 1981.

    Google Scholar 

  23. Luyckx A. S., Lefebvre P.: Possible role of endogenous prostaglandins in glucagon secretion by isolated guinea-pig islets - Diabetologia15, 411, 1978.

    Article  PubMed  Google Scholar 

  24. Luyckx A. S., Lefebvre P.: Further studies on the role of prostaglandins in glucagon secretion - In:Andreani D., Lefebvre P. J., Marks V. (Eds): Current views on hypoglycemia and glucagon. Academic Press, New York-London, 1980; p. 47.

    Google Scholar 

  25. Luyckx A. S., Lefebvre P.: Endogenous prostaglandins modulate glucagon secretion by isolated guinea-pig islets - In:Samuelsson B., Ramwell P. W., Paoletti R. (Eds): Advances in prostaglandin and thromboxane research. Raven Press, New York, 1980; p. 1299.

    Google Scholar 

  26. Malangeau P., Bourdon R., Nicaise A. M., Masson B.: Dosage des acides aminés dans les liquides de l'organisme - Ann. Biol. clin.21, 1, 1963.

    Google Scholar 

  27. Pek S., Lands E. M., Akpan J., Hurley M.: Effect of prostaglandins H2, D2, I2 and thromboxane onin vitro secretion of glucagon and insulin - In:Samuelsson B., Ramwell P. W., Paoletti R. (Eds): Advances in prostaglandin and thromboxane research. Raven Press, New York, 1980; p. 1295.

    Google Scholar 

  28. Pek S., Tai T.-Y., Crowther R., Fajans S. S.: Glucagon release precedes insulin release in response to common secretagogues - Diabetes25, 764, 1976.

    PubMed  Google Scholar 

  29. Pek S., Tai T.-Y., Elster A.: Stimulatory effects of prostaglandins E-1, E-2 and F-2-alpha on glucagon and insulin releasein vitro - Diabetes27, 801, 1978.

    PubMed  Google Scholar 

  30. Robertson R. P., Gavareski D. J., Porte D. Jr.: Inhibition ofin vivo insulin secretion by prostaglandin E1 - J. clin. Invest.54, 310, 1974.

    PubMed  Google Scholar 

  31. Snedecor G. W.: Statistical Methods - 5th ed. Iowa State University Press. Ames/Ia., 1966.

    Google Scholar 

  32. SyvÄlahti E. K. G.: The effect of indomethacin on serum growth hormone, immunoreactive insulin and blood glucose levels of young adult males - Int. J. clin. Pharmacol.10, 111, 1974.

    PubMed  Google Scholar 

  33. Tomasi V., Meringolo C., Bartolini G., Orlandi M.: Biosynthesis of prostacyclin in rat liver endothelial cells and its control by prostaglandin E2 - Nature (Lond.)273, 670, 1978.

    Article  Google Scholar 

  34. Unger R. H.: Role of glucagon in the pathogenesis of diabetes: the status of the controversy - Metabolism27, 1691, 1978.

    Article  PubMed  Google Scholar 

  35. Vane J. R.: Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs - Nature (Lond.)231, 232, 1971.

    Google Scholar 

  36. Vierhapper H.,Bratusch-Marrain P.,WaldhÄusl W.: Unchanged arginine-induced stimulation of insulin, glucagon, growth hormone and prolactin following pretreatment with indomethacin in normal man - 62nd Annual Meeting of the Endocrine Society, Washington/ D.C. 1980; abstract #40.

  37. Widström A.: Influence of indomethacin on glucose-induced insulin response in normal man. Role of prostaglandin in the rapid insulin release? - Hormone metab. Res.9, 172, 1977.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Luyckx, A.S., Guerten, D., Scheen, A. et al. Effect of indomethacin on the metabolic and hormonal response to a standardized breakfast in normal subjects. Acta diabet. lat 18, 259–266 (1981). https://doi.org/10.1007/BF02047898

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02047898

Key-words

Navigation